Antineoplastic agents d

• D1/3-mage-3-his fusion protein - A recombinant, chimeric protein derived from a melanoma antigenic epitope (MAGE-3) and recognized by specific cytotoxic T lymphocytes. MAGE-3, a human peptide epitope present in the cytosol of melanoma cells, may be expressed as the fusion protein D1/3-Mage-3; this fusion protein may boost antitumoral immune responses when used in a vaccine formulation.

• Dab389 epidermal growth factor - A recombinant fusion protein composed of the diphtheria toxin with the receptor-binding domain replaced by human epidermal growth factor (EGF). When administered, EGF binds to the endothelial cell growth factor receptor, EGFR, which is upregulated in many solid tumors. After binding to the EGF receptor, the agent is internalized by the cell, where the diphtheria toxin moiety exerts its cytotoxic effect, inhibiting protein synthesis through ADP-ribosylation of elongation factor 2.

• Dabrafenib - An orally bioavailable inhibitor of B-raf (BRAF) protein with potential antineoplastic activity. Dabrafenib selectively binds to and inhibits the activity of B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. B-raf belongs to the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations.

• Dabrafenib mesylate - The mesylate salt form of dabrafenib, an orally bioavailable inhibitor of B-raf (BRAF) protein with potential antineoplastic activity. Dabrafenib selectively binds to and inhibits the activity of B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. B-raf belongs to the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations.

• Dacarbazine - A triazene derivative with antineoplastic activity. Dacarbazine alkylates and cross-links DNA during all phases of the cell cycle, resulting in disruption of DNA function, cell cycle arrest, and apoptosis.

• Dacetuzumab - A humanized monoclonal antibody directed against the CD40 receptor with potential antineoplastic activity. Dacetuzumab specifically binds to and inhibits the CD40 receptor, thereby inducing apoptosis and inhibiting cellular proliferation via antibody-dependent cellular cytotoxicity (ADCC) in cells that overexpress this receptor. The CD40 receptor, a member of the tumor necrosis factor (TNF) receptor super-family, is highly expressed on most B lineage hematologic malignancies including multiple myeloma, non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's disease and acute lymphoblastic leukemia.

• Dach polymer platinate ap5346 - A low molecular weight polymer-conjugated platinum complex with potential antineoplastic activity. This polymer drug delivery system consists of cytotoxic diaminocyclohexane (DACH)-platinum (Pt) coupled to a water-soluble biocompatible hydroxypropylmethacrylamide (HPMA) copolymer via a pH sensitive linker. Due to decreased pH at the tumor site, the linker is cleaved and the chelated active moiety DACH-Pt is released in tumor cells. DACH-Pt alkylates macromolecules and causes both inter- and intra-strand platinum-DNA crosslinks, which impede DNA replication and transcription, thereby resulting in cell-cycle independent cytotoxicity. The HPMA-based drug delivery system enhances the concentration of DACH-Pt at the tumor site and prolongs the half life of the agent, thereby increasing exposure and efficacy at the target tumor sites while minimizing side effects in normal tissues.

• Dach-platin micelle nc-4016 - Polymeric micellar nanoparticles containing diaminocyclohexane platinum (DACH-platin or DACH-Pt) with potential antineoplastic activity. DACH-platin micelle NC-4016 is prepared through the formation of a polymer-metal complex between DACH-platin and the polyethylene glycol-poly (glutamic acid) block copolymer, PEG-P(Glu). DACH-platin, an active metabolite of the platinum-based antineoplastic agent oxaliplatin, is highly hydrophobic and toxic when administered systemically. The use of polymeric micelles incorporating DACH-platin may both increase cell permeability and enhance the retention of the agent. This allows an extended half-life in the blood circulation and a selective and high accumulation of DACH-platin at tumor sites. This results in increased anticancer efficacy while reducing side effects due to DACH-platin toxicity. Upon intravenous administration and internalization by tumor cells, DACH-platin binds to and causes both inter- and intra-strand cross-links in DNA, forming platinum adducts and triggering tumor cell apoptosis.

• Daclizumab - A recombinant monoclonal antibody interleukin-2 receptor antagonist. Daclizumab binds specifically to the alpha subunit of the human interleukin-2 (IL-2) receptor expressed on the surface of activated lymphocytes in vivo, thereby inhibiting IL-2 binding and IL-2-mediated lymphocyte activation, a critical cellular immune response pathway.

• Dacomitinib - A highly selective, orally bioavailable small-molecule inhibitor of the HER family of tyrosine kinases with potential antineoplastic activity. Dacomitinib specifically and irreversibly binds to and inhibits human Her-1, Her-2, and Her-4, resulting in the proliferation inhibition and apoptosis of tumor cells that overexpress these receptors.

• Dacplatinum - A second-generation platinum analog with potential antineoplastic activity. Dacplatinum alkylates DNA at the N-7 position of guanine, thereby producing DNA interstrand crosslinks and DNA strand breaks, and inhibiting DNA replication.

• Dactinomycin - A chromopeptide antineoplastic antibiotic isolated from the bacterium Streptomyces parvulus. Dactinomycin intercalates between adjacent guanine-cytosine base pairs, blocking the transcription of DNA by RNA polymerase; it also causes single-strand DNA breaks, possibly via a free-radical intermediate or an interaction with topoisomerase II.

• Dactolisib - An orally bioavailable imidazoquinoline targeting the phosphatidylinositol 3 kinase (PI3K) and the mammalian target of rapamycin (mTOR), with potential antineoplastic activity. Dactolisib inhibits PI3K kinase and mTOR kinase in the PI3K/AKT/mTOR kinase signaling pathway, which may result in tumor cell apoptosis and growth inhibition in PI3K/mTOR-overexpressing tumor cells. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated independent of PI3K.

• Dactolisib tosylate - The tosylate salt form of dactolisib, an orally bioavailable imidazoquinoline targeting the phosphatidylinositol 3 kinase (PI3K) and the mammalian target of rapamycin (mTOR), with potential antineoplastic activity. Upon administration, dactolisib inhibits PI3K kinase and mTOR kinase in the PI3K/AKT/mTOR kinase signaling pathway, which may result in tumor cell apoptosis and growth inhibition in PI3K/mTOR-overexpressing tumor cells. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy. mTOR, a serine/threonine kinase downstream of PI3K, may also be activated independent of PI3K.

• Dalantercept - A soluble fusion protein containing the extracellular domain of activin receptor-like kinase-1 (ALK1) fused to a human Fc domain (ALK1-Fc fusion protein), with potential antiangiogenic and antineoplastic activities. Upon administration, dalantercept binds to various ALK1 ligands, preventing activation of tumor cell ALK1 receptors and so inhibiting the ALK1 signaling pathway; growth factor-induced angiogenesis is thus inhibited, which may result in the inhibition of tumor cell proliferation and tumor cell death. ALK1 is a type I cell surface receptor with serine/threonine kinase activity that mediates signaling by members of the transforming growth factor-beta (TGFbeta) superfamily and plays a key role in angiogenesis; ligands for this receptor include TGFbeta1 and TGFbeta2. The Fc moiety of this fusion protein mediates clearance of ligand-fusion protein complexes by the reticuloendothelial system (RES).

• Dalotuzumab - A recombinant humanized monoclonal antibody directed against the insulin-like growth factor 1 receptor (IGF1R) with potential antineoplastic activity. Dalotuzumab binds to membrane-bound IGF1R, preventing binding of the ligand IGF1 and the subsequent triggering of the PI3K/Akt signaling pathway; inhibition of this survival signaling pathway may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. The activation of IGF1R, a tyrosine kinase and a member of the insulin receptor family, stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF1R signaling has been highly implicated in tumorigenesis and metastasis.

• Daniquidone - A water-insoluble heterocyclic amide with potential antineoplastic activity. Daniquidone inhibits topoisomerases I and II, thereby inhibiting DNA replication and repair, and RNA and protein synthesis. The acetylated form of daniquidone is highly toxic and is capable of inducing unscheduled DNA synthesis; rapid acetylators are more likely to experience toxicity with this agent.

• Danusertib - A small-molecule 3-aminopyrazole derivative with potential antineoplastic activity. Danusertib binds to and inhibits the Aurora kinases, which may result in cell growth arrest and apoptosis in tumor cells in which Aurora kinases are overexpressed. This agent may preferentially bind to and inhibit Aurora B kinase. Aurora kinases, a family of serine-threonine kinases, are important regulators of cellular proliferation and division.

• Danvatirsen - An antisense oligonucleotide targeting signal transducer and activator of transcription 3 (STAT3) with potential antitumor activity. Danvatirsen binds to STAT3 mRNA, thereby inhibiting translation of the transcript. Suppression of STAT3 expression induces tumor cell apoptosis and decreases tumor cell growth. STAT3, a protein overexpressed in a variety of human cancers, plays a critical role in tumor cell growth and survival.

• Daporinad - A small molecule with potential antineoplastic and antiangiogenic activities. Daporinad binds to and inhibits nicotinamide phosphoribosyltransferase (NMPRTase), inhibiting the biosynthesis of nicotinamide adenine dinucleotide (NAD+) from niacinamide (vitamin B3), which may deplete energy reserves in metabolically active tumor cells and induce tumor cell apoptosis. In addition, this agent may inhibit tumor cell production of vascular endothelial growth factor (VEGF), resulting in the inhibition of tumor angiogenesis. The coenzyme NAD+ plays an essential role in cellular redox reactions, including the redox reaction linking the citric acid cycle and oxidative phosphorylation.

• Daratumumab - A fully human monoclonal antibody directed against the cell surface glycoprotein CD-38 with potential antineoplastic activity. The binding of anti-CD38 monoclonal antibody to natural killer (NK) cells mimics the normal CD38-CD31 interaction on the NK cell surface. CD38 is also present on multiple myeloma (MM) cells and plasma leukemia cells; this agent may preferentially bind these cells, triggering antitumoral antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). CD38, a cell surface glycoprotein, is present on various immune cells and has been shown to regulate the cytotoxic response of activated NK cells.

• Daratumumab and hyaluronidase-fihj - A co-formulation composed of daratumumab, a human immunoglobulin (Ig) G1 kappa monoclonal antibody directed against the cell surface glycoprotein cluster of differentiation 38 (CD-38; CD38), and a recombinant form of human hyaluronidase (rHuPH20), with potential antineoplastic activity. Upon subcutaneous administration of daratumumab and hyaluronidase-fihj, daratumumab targets and binds to CD38 on certain CD38-expressing tumors, such as multiple myeloma (MM) and plasma cell leukemia. This binding induces direct apoptosis through Fc-mediated cross-linking and triggers immune-mediated tumor cell lysis through antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP) immune responses. CD38, a transmembrane glycoprotein, is expressed in both hematopoietic and non-hematopoietic lineage cells. Hyaluronidase-fihj hydrolyzes and degrades the glycosaminoglycan hyaluronic acid (HA), thereby decreasing interstitial viscosity and enhancing penetration of daratumumab through the interstitial space. This facilitates the delivery of daratumumab to CD38-expressing tumor cells.

• Darinaparsin - A small-molecule organic arsenical with potential antineoplastic activity. Although the exact mechanism of action is unclear, darinaparsin, a highly toxic metabolic intermediate of inorganic arsenicals (iAs) that occurs in vivo, appears to generate volatile cytotoxic arsenic compounds when glutathione (GSH) concentrations are low. The arsenic compounds generated from darinaparsin disrupt mitochondrial bioenergetics, producing reactive oxygen species (ROS) and inducing ROS-mediated tumor cell apoptosis; in addition, this agent or its byproducts may initiate cell death by interrupting the G2/M phase of the cell cycle and may exhibit antiangiogenic effects. Compared to inorganic arsenic compounds such as arsenic trioxide (As2O3), darinaparsin appears to exhibit a wide therapeutic window.

• Darleukin - An immunoconjugate consisting of the recombinant form of the cytokine interleukin-2 (IL-2) fused to a human single-chain Fv (scFv) antibody fragment directed against the extra-domain B (ED-B) of fibronectin (L19), with potential immunopotentiating and antineoplastic activities. The L19 moiety of L19-IL2 monoclonal antibody-cytokine fusion protein binds to the ED-B domain of fibronectin on tumor cells in the tumor neovasculature. In turn, the IL-2 moiety may locally activate natural killer (NK) cells and macrophages, and may induce T cell cytotoxic immune responses against ED-B fibronectin-expressing tumor cells. This may specifically decrease the proliferation of ED-B-expressing tumor cells. ED-B is predominantly expressed during angiogenesis and tumor growth.

• Darolutamide - A formulation containing an androgen receptor (AR) antagonist with potential antineoplastic activity. Darolutamide binds to ARs in target tissues; subsequently, inhibiting androgen-induced receptor activation and facilitating the formation of inactive complexes that cannot translocate to the nucleus. This prevents binding to and transcription of AR-responsive genes that regulate prostate cancer cell proliferation. This ultimately leads to an inhibition of growth in AR-expressing prostate cancer cells.

• Daromun - A combination of darleukin (L19-IL2), an immunocytokine consisting of the recombinant form of interleukin-2 (IL-2), fused to a human single-chain variable fragment (scFv) directed against the extra-domain B (ED-B) of fibronectin (L19), and fibromun (L19-TNFalpha), an immunocytokine consisting of human tumor necrosis factor alpha (TNFalpha) fused to a human scFv antibody fragment directed against the ED-B of L19, with potential antineoplastic and immunostimulating activities. Upon administration, the L-19 moieties of each immunocytokine bind to the ED-B domain of fibronectin on tumor cells in the tumor neovasculature. In turn, the IL-2 and TNF-alpha moieties of darleukin and fibromun, respectively, may locally induce an immune response against ED-B fibronectin-expressing tumor cells. ED-B is predominantly expressed during angiogenesis and tumor growth.

• Dasatinib - An orally bioavailable synthetic small molecule-inhibitor of SRC-family protein-tyrosine kinases. Dasatinib binds to and inhibits the growth-promoting activities of these kinases. Apparently because of its less stringent binding affinity for the BCR-ABL kinase, dasatinib has been shown to overcome the resistance to imatinib of chronic myeloid leukemia (CML) cells harboring BCR-ABL kinase domain point mutations. SRC-family protein-tyrosine kinases interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways; tumorigenic forms can occur through altered regulation or expression of the endogenous protein and by way of virally-encoded kinase genes.

• Daunorubicin - An anthracycline antineoplastic antibiotic with therapeutic effects similar to those of doxorubicin. Daunorubicin exhibits cytotoxic activity through topoisomerase-mediated interaction with DNA, thereby inhibiting DNA replication and repair and RNA and protein synthesis.

• Daunorubicin citrate - A semi-synthetic anthracycline glycoside antibiotic obtained from Streptomyces with antineoplastic activity. Daunorubicin citrate intercalates DNA, which leads to inhibition of DNA and RNA synthesis, and consequently blocks cell division and results in apoptosis. This anti-tumor antibiotic is most active in the S phase of cell division. Daunorubicin is indicated in the treatment of a wide variety of cancers including acute non-lymphocytic leukemia, non-Hodgkin lymphomas, Ewing's sarcoma, Wilms' tumor, and chronic myelocytic leukemia. (NCI05)

• Daunorubicin hydrochloride - The hydrochloride salt of an anthracycline antineoplastic antibiotic with therapeutic effects similar to those of doxorubicin. Daunorubicin exhibits cytotoxic activity through topoisomerase-mediated interaction with DNA, thereby inhibiting DNA replication and repair and RNA and protein synthesis.

• Dc-ova vaccine - An autologous, multivalent dendritic cell vaccine targeting ovarian cancer with potential immunostimulating and antineoplastic activities. DC-OVA vaccine is produced in vitro by pulsing autologous dendritic cells with killed autologous primary ovarian tumors as a source of tumor-associated antigens (TAAs); the pulsed DCs are then matured using various cytokines. Upon administration, DC-OVA vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against ovarian cancer TAA-expressing ovarian cancer cells.

• Dcr ligand-bearing liposome-encapsulated melanoma antigens vaccine - A cancer cell-based vaccine containing liposome encapsulated melanoma antigens and an immunomodulatory factor, attached, via a metal chelator, to a dendritic cell receptor (DCR) ligand-containing a metal-affinity tag, with potential immunomodulating and antineoplastic activity. Upon intravenous administration of DCR ligand-bearing liposome-encapsulated melanoma antigens vaccine, the DCR ligand moiety of this vaccine targets receptors on dendritic cells (DCs), thereby presenting the antigens to DCs which may, in turn, stimulate the DCs and may activate the immune system to mount a cytotoxic T lymphocyte (CTL) response against melanoma cancer cell associated antigens.

• Dec-205/ny-eso-1 fusion protein cdx-1401 - A fusion protein consisting of a fully human monoclonal antibody directed against the endocytic dendritic cell (DC) receptor, DEC-205, linked to the tumor-associated antigen (TAA) NY-ESO-1 with potential immunostimulating and antineoplastic activities. The monoclonal antibody moiety of DEC-205/NY-ESO-1 fusion protein CDX-1401 binds to the endocytic DC receptor, which may result in DC endocytic internalization of this agent, specifically delivering the NY-ESO-1 moiety. DC processing of NY-ESO-1 may boost the immune system to mount a cytotoxic T-lymphocyte response (CTL) against cancer cells expressing NY-ESO-1. NY-ESO-1, a cell surface protein expressed in normal fetal and adult testes, is upregulated in a variety of tumor cell types.

• Decitabine - A cytidine antimetabolite analogue with potential antineoplastic activity. Decitabine incorporates into DNA and inhibits DNA methyltransferase, resulting in hypomethylation of DNA and intra-S-phase arrest of DNA replication.

• Decitabine and cedazuridine - An orally available fixed-dose combination agent containing cedazuridine, a cytidine deaminase (CDA) inhibitor, and the cytidine antimetabolite decitabine, with potential antineoplastic activity. Upon oral administration of tdecitabine and cedazuridine, cedazuridine binds to and inhibits CDA, an enzyme primarily found in the gastrointestinal (GI) tract and liver that catalyzes the deamination of cytidine and cytidine analogs. This prevents the breakdown of decitabine, increases its bioavailability and efficacy while decreasing GI toxicity due to the administration of lower doses of decitabine. Decitabine exerts its antineoplastic activity through the incorporation of its triphosphate form into DNA, which inhibits DNA methyltransferase and results in hypomethylation of DNA. This interferes with DNA replication and decreases tumor cell growth.

• Defactinib - An orally bioavailable, small-molecule focal adhesion kinase (FAK) inhibitor with potential antiangiogenic and antineoplastic activities. Defactinib inhibits FAK, which may prevent the integrin-mediated activation of several downstream signal transduction pathways, including those involving RAS/MEK/ERK and PI3K/Akt, thus inhibiting tumor cell migration, proliferation, survival, and tumor angiogenesis. The tyrosine kinase FAK, a signal transducer for integrins, is normally activated by binding to integrins in the extracellular matrix (ECM) but may be upregulated and constitutively activated in various tumor cell types.

• Defactinib hydrochloride - The hydrochloride salt form of defactinib, an orally bioavailable, small-molecule focal adhesion kinase (FAK) inhibitor with potential antiangiogenic and antineoplastic activities. Defactinib inhibits FAK, which may prevent the integrin-mediated activation of several downstream signal transduction pathways, including those involving RAS/MEK/ERK and PI3K/Akt, thus inhibiting tumor cell migration, proliferation, survival, and tumor angiogenesis. The tyrosine kinase FAK, a signal transducer for integrins, is normally activated by binding to integrins in the extracellular matrix (ECM) but may be upregulated and constitutively activated in various tumor cell types.

• Deferoxamine - An iron-chelating agent that binds free iron in a stable complex, preventing it from engaging in chemical reactions. Deferoxamine chelates iron from intra-lysosomal ferritin and siderin forming ferrioxamine, a water-soluble chelate excreted by the kidneys and in the feces via the bile. This agent does not readily bind iron from transferrin, hemoglobin, myoglobin or cytochrome.

• Deferoxamine hydrochloride - The hydrochloride salt form of deferoxamine, an iron chelating agent. Deferoxamine chelates iron from intra-lysosomal ferritin and hemosiderin forming ferrioxamine, a water-soluble chelate excreted by the kidneys and in the feces via the bile. This agent does not readily bind iron from transferrin, hemoglobin, myoglobin or cytochrome. (NCI)

• Deferoxamine mesylate - The mesylate salt of an iron-chelating agent that binds free iron in a stable complex, preventing it from engaging in chemical reactions. Deferoxamine chelates iron from intra-lysosomal ferritin and ferrioxamine, a water-soluble complex excreted by the kidneys and in the feces via the bile. This agent does not readily chelate iron bound to transferrin, hemoglobin, myoglobin or cytochrome.

• Degarelix - A long-acting, synthetic peptide with gonadotrophin-releasing hormone (GnRH) antagonistic properties. Degarelix targets and blocks GnRH receptors located on the surfaces of gonadotroph cells in the anterior pituitary, thereby reducing secretion of luteinizing hormone (LH) by pituitary gonadotroph cells and so decreasing testosterone production by interstitial (Leydig) cells in the testes.

• Degarelix acetate - The acetate form of a long-acting, synthetic peptide with gonadotrophin-releasing hormone (GnRH) antagonistic properties. Degarelix targets and blocks GnRH receptors located on the surfaces of gonadotroph cells in the anterior pituitary, thereby reducing secretion of luteinizing hormone (LH) by pituitary gonadotroph cells and so decreasing testosterone production by interstitial (Leydig) cells in the testes.

• Deglycosylated ricin a chain-conjugated anti-cd19/anti-cd22 immunotoxins - A combination preparation of 1:1 mixture of two immunotoxins, HD37-dgA and RFB4-dgA, with potential antineoplastic activity. Both anti-CD19 IgG monoclonal antibody HD37 and anti-CD22 IgG monoclonal antibody RFB4 are attached to a single deglycosylated ricin A chain (dgA) via N-succinimidyl-oxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio) toluene (SMPT) linker. CD19 and CD22 molecules are cell suface antigens present on the majority of B acute lymphoblastic leukemia cells. This combination agent is able to specifically recognize and bind to CD19 and CD22 expressing tumor cells, thereby targeting the delivery of the cytotoxic ricin A chain to leukemia cells expressing these antigens. Ricin A chain is toxic to ribosomal activity and protein synthesis, and inhibits cell growth.

• Delanzomib - An orally bioavailable synthetic P2 threonine boronic acid inhibitor of the chymotrypsin-like activity of the proteasome, with potential antineoplastic activity. Delanzomib represses the proteasomal degradation of a variety of proteins, including inhibitory kappaBalpha (IkappaBalpha), resulting in the cytoplasmic sequestration of the transcription factor NF-kappaB; inhibition of NF-kappaB nuclear translocation and transcriptional up-regulation of a variety of cell growth-promoting factors; and apoptotic cell death in susceptible tumor cell populations. In vitro studies indicate that this agent exhibits a favorable cytotoxicity profile toward normal human epithelial cells, bone marrow progenitors, and bone marrow-derived stromal cells relative to the proteasome inhibitor bortezomib. The intracellular protein IkappaBalpha functions as a primary inhibitor of the proinflammatory transcription factor NF-kappaB.

• Delolimogene mupadenorepvec - A double-armed oncolytic adenovirus composed of a recombinant genetically modified E1/E3-deleted, adenoviral serotype 5 (Ad5) vector, with the L5 segment of the Ad5 fiber replaced by the shaft and knob from the Ad35 serotype (Ad5/35), which expresses a trimerized (TMZ) form of the membrane-bound immunostimulator CD40 ligand (CD40L; TNFSF5) and the ligand for the signaling domain 4-1BB (4-1BBL; CD137L; TNFSF9), under the control of a CMV promoter, with potential immunostimulating and antineoplastic activities. Upon intratumoral administration of delolimogene mupadenorepvec, the virus infects and selectively replicates in tumor cells. This causes direct oncolysis and the release of a plethora of tumor-associated antigens (TAAs) from the tumor cells. The released TAAs stimulate the immune system and activate anti-tumor cytotoxic T-lymphocytes (CTLs), thereby further killing tumor cells. In addition, infected tumor cells and tumor stroma cells, including stellate cells and infiltrating immune cells, express the immunostimulants CD40L and 4-1BBL. The expressed CD40L and 4-1BBL proteins activate the CD40L- and 4-1BBL-mediated signaling pathways, respectively. This activates antigen-presenting cells (APCs), such as dendritic cells (DCs) and M1 macrophages. The DCs produce various cytokines, including interleukin-12 (IL12), IL21, tumor necrosis factor-alpha (TNFa), and interferon-gamma (IFNg), which leads to the activation and expansion of both T-cells and natural killer (NK) cells. Altogether, this modulates immune suppression in the tumor microenvironment (TME), disrupts tumor stroma, and causes additional immune stimulation against tumor cells, thereby inducing further tumor cell lysis. In addition, CD40L reduces myeloid suppressor cells in the TME. Inclusion of the chimeric Ad5/35 fiber targets CD46 and increases viral uptake in cells. Transgene expression is driven by a separate promoter to allow for efficient expression in both tumor cells and tumor stroma. Replication is restricted to tumor cells by the presence of the delta24 mutation in the E1A gene, which deletes the retinoplastoma protein (pRb)-binding domain and forces viral replication to be conditional on hyperphosphorylated pRb and a dysfunctional Rb pathway.

• Demcizumab - A humanized monoclonal antibody directed against the N-terminal epitope of Notch ligand DLL4 (delta-like 4) with potential antineoplastic activity. Demcizumab binds to the membrane-binding portion of DLL4 and prevents its interaction with Notch-1 and Notch-4 receptors, thereby inhibiting Notch-mediated signaling and gene transcription, which may impede tumor angiogenesis. Activation of Notch receptors by DLL4 stimulates proteolytic cleavage of the Notch intracellular domain (NICD); after cleavage, NICD is translocated into the nucleus and mediates the transcriptional regulation of a variety of genes involved in vascular development. The expression of DLL4 is highly restricted to the vascular endothelium.

• Demecolcine - A colchicine analog with potential antimitotic and antineoplastic activities. Demecolcine acid binds to the colchicine-binding site of tubulin, inhibiting its polymerization into microtubules, causing cell cycle arrest at metaphase and preventing cell division.

• Demplatin pegraglumer - A nanoparticle-based prodrug formulation consisting of polymeric micelles incorporating the inorganic platinum agent cisplatin with potential antineoplastic activity. In demplatin pegraglumer, cisplatin forms a polymer-metal complex with hydrophilic polyethylene glycol poly(glutamic acid) block copolymers by attaching to the micelle inner core consisting of the hydrophobic polyamino acids. Upon cell entry and release from the polymer-metal complex, cisplatin forms highly reactive, charged platinum complexes that bind to nucleophilic groups such as GC-rich sites in DNA, inducing intrastrand and interstrand DNA cross-linking, DNA-protein cross-linking and, subsequently, tumor cell apoptosis and growth inhibition. Due to the hydrophilic nature of polyethylene glycol, this formulation increases the water-solubility of cisplatin and decreases the nephrotoxicity and neurotoxicity associated with the administration of cisplatin alone.

• Dendrimer-conjugated bcl-2/bcl-xl inhibitor azd0466 - A drug-dendrimer conjugate composed of a B-cell lymphoma 2 (Bcl-2)/Bcl-XL inhibitor AZD4320 that is chemically conjugated to a proprietary 5-generation pegylated poly-lysine dendrimer via a hydrolytically labile linker, with potential pro-apoptotic and antineoplastic activities. Upon administration of AZD0466, AZD4320 is released through hydrolytic cleavage of the linker. AZD4320 is a Bcl2-homology domain 3 (BH3) mimetic that specifically binds to and inhibits the activity of the anti-apoptotic proteins Bcl-2 and Bcl-XL. This restores apoptotic processes and inhibits cell proliferation in Bcl-2/Bcl-XL-dependent tumor cells. Bcl-2 and Bcl-XL, proteins belonging to the Bcl-2 family that are overexpressed in many cancers, play an important role in the negative regulation of apoptosis. Their expression in tumors is associated with increased drug resistance and cancer cell survival. The conjugation of AZD 4320 to the dendrimer construct may allow extended release of the agent, which may improve efficacy and lower toxicity.

• Dendritic cell tumor cell lysate vaccine - A vaccine composed of dendritic cells pulsed with tumor cells lysates that stimulate a potent and specific cell mediated anti-tumor immune response. (NCI)

• Dendritic cell tumor peptide vaccine - A vaccine composed of dendritic cells pulsed with peptide epitopes that stimulate cytotoxic T lymphocyte anti-tumor activity. (NCI)

• Dendritic cell-autologous lung tumor vaccine - A cancer vaccine consisting of lymphocytes harvested from a patient with lung cancer and induced to become antigen-presenting cells (APCs) known as dendritic cells. The dendritic cells are transduced with the gene encoding an antigen specific to the patient's cancer and then returned to the patient. In the host, the altered cells stimulate the immune system to mount a primary T cell response against lung tumor cells expressing the target antigen. Dendritic cell-autologous lung tumor vaccines have been investigated for use in cancer immunotherapy.

• Dendritic cell-cea peptide vaccine - A cancer vaccine consisting of dendritic cells harvested from a patient with cancer and pulsed or transduced with a peptide fragment of carcinoembryonic antigen (CEA), a tumor-associated antigen expressed by a wide range of cancers. When the altered dendritic cells are returned to the patient, they may stimulate the host immune system to mount a cytotoxic T-lymphocyte immune response against tumor cells expressing CEA.

• Dendritic cell-gp100-mart-1 antigen vaccine - An autologous dendritic cells vaccine with antineoplastic property. Dendritic cells harvested from cancer patients are pulsed with human gp100 melanoma antigen and MART-1 (melanoma antigen recognized by T-cells) antigen; both antigens are up-regulated in melanomas. Vaccination with this vaccine may elicit the host immune response against MART-1 or gp100 expressing cells.

• Dendritic cell-idiotype-keyhole limpet hemocyanin vaccine - A cell-based vaccine composed of allogeneic dendritic cells (DC), pulsed with patient-specific non-Hodgkin's lymphoma idiotype (Id) determinants conjugated to keyhole limpet hemocyanin (KLH), with potential antitumor activity. Upon administration, this vaccine may stimulate the host immune system to mount a specific cytotoxic T-lymphocyte (CTL) response against Id-expressing lymphoma cells, resulting in tumor cell lysis.

• Dendritic cell-mart-1 peptide vaccine - A cancer vaccine consisting of dendritic cells harvested from a patient with cancer and pulsed or transduced with a peptide fragment of MART-1 (melanoma antigen recognized by T-cells), an antigen expressed by melanoma cells. When the altered dendritic cells are returned to the patient, they stimulate the host immune system to mount a cytotoxic T-lymphocyte immune response against tumor cells expressing MART-1.

• Dendritic cell-precision multiple antigen t-lymphocytes - A preparation of dendritic cell-precision multiple antigen T-cells (DC-PMAT) that have been induced to specifically target multiple undisclosed tumor-associated antigens (TAAs), with potential antitumor activity. Although the exact mechanism(s) of action through which DC-PMAT cells exert their effects has yet to be elucidated, upon infusion, these cells may stimulate the host immune system to mount a highly-specific cytotoxic T-lymphocyte (CTL) response against tumors expressing common TAAs, which leads to tumor cell lysis.

• Dendritic cell-targeting lentiviral vector id-lv305 - An engineered lentiviral vector targeting dendritic cells (DCs) and containing nucleic acids encoding for the human tumor-associated cancer-testis antigen NY-ESO-1, with potential immunostimulatory and antineoplastic activities. Upon intradermal administration, the DC-targeting lentiviral vector ID-LV305 targets and binds to dermal DCs via the DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) receptor. Upon internalization of the vector, the NY-ESO-1 protein is expressed, stimulates DC maturation and activates the immune system to mount a cytotoxic T-lymphocyte (CTL) response against NY-ESO-1-expressing cells, which may result in tumor cell lysis. NY-ESO-1 is expressed in normal testes and on the surfaces of various tumor cells, and plays a key role in tumor cell proliferation and survival.

• Denenicokin - A recombinant peptide similar to or identical to endogenous human cytokine interleukin-21 (IL-21) with potential antineoplastic activity. Denenicokin binds to and activates IL-21 receptors, expressed on T-cells, B-cells, dendritic cells (DC), and natural killer (NK) cells, modulating the proliferation and/or differentiation of T and B cells, promoting T cell survival, and increasing the cytolytic activity of cytotoxic T lymphocytes (CTLs) and NK cells.

• Dengue virus adjuvant pv-001-dv - 45AZ5, with potential immunostimulating activity. Upon administration of dengue virus adjuvant PV-001-DV, the virus may activate both the innate and adaptive immune system.

• Denibulin - A small molecular vascular disrupting agent (VDA), with potential antimitotic and antineoplastic activities. Denibulin selectively targets and reversibly binds to the colchicine-binding site on tubulin and inhibits microtubule assembly. This results in the disruption of the cytoskeleton of tumor endothelial cells, ultimately leading to cell cycle arrest, blockage of cell division and apoptosis. This causes inadequate blood flow to the tumor and eventually leads to a decrease in tumor cell proliferation.

• Denibulin hydrochloride - The hydrochloride salt of denibulin, a small molecular vascular disrupting agent, with potential antimitotic and antineoplastic activities. Denibulin selectively targets and reversibly binds to the colchicine-binding site on tubulin and inhibits microtubule assembly. This results in the disruption of the cytoskeleton of tumor endothelial cells, ultimately leading to cell cycle arrest, blockage of cell division and apoptosis. This causes inadequate blood flow to the tumor and eventually leads to a decrease in tumor cell proliferation., a small molecule vascular disrupting agent (VDA), with potential antimitotic and antineoplastic activity. Denibulin selectively targets and reversibly binds to the colchicine-binding site on tubulin and inhibits microtubule assembly. This results in the disruption of the cytoskeleton of tumor endothelial cells (EC), ultimately leading to cell cycle arrest, blockage of cell division and apoptosis. This causes inadequate blood flow to the tumor and eventually leads to a decrease in tumor cell proliferation.

• Denileukin diftitox - A cytotoxic recombinant protein consisting of interleukin-2 (IL-2) protein sequences fused to diphtheria toxin. The IL-2 protein sequence moiety of denileukin difitox directs the cytocidal action of diphtheria toxin to cells that express IL-2 receptors. After the toxin moiety is internalized into target IL-2 receptor-expressing cells, its catalytic domain catalyzes the transfer of the ADP-ribose moiety of NAD to a posttranslationally modified histidine residue of elongation factor 2 (EF-2), called diphthamine. This covalent modification inactivates EF-2 and disrupts polypeptide chain elongation, resulting in cell death.

• Denintuzumab mafodotin - An immunoconjugate consisting of an anti-CD19 monoclonal antibody conjugated to the auristatin derivative monomethyl auristatin F (MMAF), with potential antineoplastic activity. Upon administration of denintuzumab mafodotin, the antibody moiety targets the cell surface antigen CD19, found on a number of B-cell-derived cancers. Upon antibody/antigen binding and internalization, the immunoconjugate releases MMAF, which binds to tubulin and inhibits its polymerization. Inhibition of tubulin polymerization may result in G2/M phase arrest and tumor cell apoptosis. This causes inhibition of cell growth of CD19-expressing tumor cells. CD19, a B-cell antigen, is overexpressed by a variety of different cancer cell types.

• Denosumab - A fully human monoclonal antibody directed against the receptor activator of nuclear factor kappa beta ligand (RANKL) with antiosteoclast activity. Denosumab specifically binds to RANKL and blocks the interaction of RANKL with RANK, a receptor located on osteoclast cell surfaces, resulting in inhibition of osteoclast activity, a decrease in bone resorption, and a potential increase in bone mineral density. RANKL, a protein expressed by osteoblastic cells, plays an important role in osteoclastic differentiation and activation.

• Depatuxizumab - A humanized monoclonal antibody (MoAb) against human epidermal growth factor receptor (EGFR) with antineoplastic activity. Depatuxizumab targets the EGFR deletion variant, de2-7 EGFR as well as wild-type EGFR expressed in cells overexpressing the receptor, thereby preventing the activation and subsequent dimerization of the receptor; the decrease in receptor activation and dimerization result in an inhibition in signal transduction and anti-proliferative effects. This MoAb targets cells expressing aberrant EGFR, hence making it an ideal candidate for generation of radioisotope or toxin conjugates.

• Depatuxizumab mafodotin - An epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon intravenous infusion, depatuxizumab mafodotin inhibits the activity of EGFR, thereby preventing EGFR-mediated signaling. This may inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase overexpressed in certain tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.

• Depdc1/mphosh1 peptide vaccine - A cancer vaccine containing HLA-A*2402-restricted epitopes derived from DEP domain containing 1 (DEPDC1) and M phase phosphoprotein 1 (MPHOSPH1) with potential immunostimulatory and antineoplastic activities. Upon administration, DEPDC1/MPHOSH1 peptide vaccine may elicit a specific cytotoxic T lymphocyte (CTL) response against tumor cells expressing DEPDC1 and MPHOSPH1, tumor antigens that are overexpressed in bladder cancer cells.

• Derazantinib - An orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) with potential antineoplastic activity. Derazantinib binds to and potently inhibits the activity of FGFR subtypes 1, 2 and 3. This may result in the inhibition of FGFR-mediated signal transduction pathways, tumor cell proliferation, tumor angiogenesis and tumor cell death in FGFR-overexpressing tumor cells. FGFR, a receptor tyrosine kinase, is upregulated in many tumor cell types and plays a key role in tumor cellular proliferation, differentiation, angiogenesis and survival.

• Deslorelin - A synthetic nonapeptide analogue of the natural gonadotrophin releasing hormone (GnRH) with potential antineoplastic activity. Deslorelin binds to and activates pituitary gonadotropin releasing hormone (GnRH) receptors. Continuous, prolonged administration of goserelin in males results in pituitary GnRH receptor desensitization and inhibition of pituitary secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH), leading to a significant decline in testosterone production; in females, prolonged administration results in a decrease in estradiol production.

• Deslorelin acetate - A synthetic nonapeptide analogue of the natural gonadotrophin releasing hormone (GnRH) with potential antineoplastic activity. Deslorelin binds to and activates pituitary gonadotropin releasing hormone (GnRH) receptors. Continuous, prolonged administration of goserelin in males results in pituitary GnRH receptor desensitization and inhibition of pituitary secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH), leading to a significant decline in testosterone production; in females, prolonged administration results in a decrease in estradiol production.

• Detirelix -

• Detorubicin - A semi-synthetic derivative of the anthracycline antineoplastic antibiotic daunorubicin. Detorubicin intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair and RNA and protein synthesis. This agent also produces toxic free-radical intermediates and interacts with cell membrane lipids causing lipid peroxidation. Detorubicin is less toxic than daunorubicin.

• Deuterated enzalutamide - A deuterated form of enzalutamide, an orally bioavailable, organic, non-steroidal small molecule targeting the androgen receptor (AR) with potential antineoplastic activity. Upon administration, deuterated enzalutamide competitively binds to and inhibits the activity of ARs expressed on prostate cancer cells, which impairs nuclear translocation and DNA binding, resulting in apoptosis of prostate cancer cells. This results in a reduction in prostate cancer cell growth. AR overexpression in prostate cancer represents a key mechanism associated with prostate cancer hormone resistance. Deuterium incorporation, by replacing the hydrogen atoms of the N-CH3 moiety with deuterium atoms, decreases enzalutamide's metabolism and allows for an increased pharmacokinetic profile, thereby enhancing its anti-tumor efficacy compared to non-deuterated enzalutamide. As the deuterated form can't cross the blood-brain barrier (BBB), the deuterated form also reduces the unwanted brain-related side effects of enzalutamide and improves its safety profile.

• Devimistat - A racemic mixture of the enantiomers of a synthetic alpha-lipoic lipoic acid analogue with potential chemopreventive and antineoplastic activities. Although the exact mechanism of action is unknown, devimistat has been shown to inhibit metabolic and regulatory processes required for cell growth in solid tumors. Both enantiomers in the racemic mixture exhibit antineoplastic activity.

• Dexamethasone - A synthetic adrenal corticosteroid with potent anti-inflammatory properties. In addition to binding to specific nuclear steroid receptors, dexamethasone also interferes with NF-kB activation and apoptotic pathways. This agent lacks the salt-retaining properties of other related adrenal hormones.

• Dexanabinol - A synthetic, terpene-based cannabinoid derivative devoid of cannabinoid receptors 1 and 2 agonist activity and with potential neuroprotective, antiinflammatory and antineoplastic activities. Functioning as an N-Methyl-D-aspartate (NMDA) receptor antagonist, dexanabinol protects neuronal cells against NMDA and glutamate neurotoxicity. This agent also scavenges peroxy radicals and protects neurons from the damages of reactive oxygen species. Furthermore, dexanabinol inhibits the activity of nuclear factor kappa B (NF-kB), thereby preventing the expression of NF-kB target genes, such as tumor necrosis factor alpha, cytokines and inducible nitric oxide synthase. As a result, this agent may restore apoptotic processes in cancerous cells. NF-kB is activated in a variety of cancer cells and plays a key role in the regulation of apoptosis and cellular proliferation.

• Dexrazoxane - A bisdioxopiperazine with iron-chelating, chemoprotective, cardioprotective, and antineoplastic activities. After hydrolysis to an active form that is similar to ethylenediaminetetraacetic acid (EDTA), dexrazoxane chelates iron, limiting the formation of free radical-generating anthracycline-iron complexes, which may minimize anthracycline-iron complex-mediated oxidative damage to cardiac and soft tissues. This agent also inhibits the catalytic activity of topoisomerase II, which may result in tumor cell growth inhibition.

• Dexrazoxane hydrochloride - The hydrochloride salt of a bisdioxopiperazine with iron-chelating, chemoprotective, cardioprotective, and antineoplastic activities. After hydrolysis to an active form that is similar to ethylenediaminetetraacetic acid (EDTA), dexrazoxane chelates iron, limiting the formation of free radical-generating anthracycline-iron complexes, which may minimize anthracycline-iron complex-mediated oxidative damage to cardiac and soft tissues. This agent also inhibits the catalytic activity of topoisomerase II, which may result in tumor cell growth inhibition.

• Dezaguanine - A purine nucleoside analogue with antineoplastic and antiviral activities. By replacing guanine, dezaguanine incorporates into DNA and inhibits de novo purine synthesis, thereby inducing cell death. (NCI)

• Dezaguanine mesylate - The mesylate salt form of dezaguanine, a purine nucleoside analogue with antineoplastic and antiviral activities. By competing with guanine, dezaguanine gets incorporated into DNA and inhibits DNA synthesis, thereby inducing cell death.

• Dezapelisib - An orally bioavailable, selective inhibitor of the delta isoform of the 110 kDa catalytic subunit of class I phosphoinositide-3 kinases (PI3K) with potential antineoplastic activity. Dezapelisib specifically inhibits PI3Kdelta, which prevents both the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) and the activation of the PI3K/AKT kinase signaling pathway. This decreases proliferation and induces cell death in PI3K-overexpressing tumor cells. Unlike other isoforms of PI3K, PI3Kdelta is often overexpressed in tumor cells, especially those of hematologic origin, and plays a crucial role in tumor cell regulation and survival. The targeted inhibition of PI3Kdelta allows for PI3K signaling in normal, non-neoplastic cells.

• Dha-paclitaxel - A prodrug comprised of the naturally occurring omega-3 fatty acid docosahexaenoic acid (DHA) covalently conjugated to the anti-microtubule agent paclitaxel. Because tumor cells take up DHA, DHA-paclitaxel is delivered directly to tumor tissue, where the paclitaxel moiety binds to tubulin and inhibits the disassembly of microtubules, thereby resulting in the inhibition of cell division. Paclitaxel also induces apoptosis by binding to and blocking the function of the apoptosis inhibitor protein Bcl-2 (B-cell Leukemia 2). DHA-paclitaxel exhibits improved pharmacokinetic and toxicity profiles when compared to conventional paclitaxel and has demonstrated antineoplastic activity in animal models of cancer.

• Dhea mustard - A steroidal alkylating agent with potential antineoplastic activity. Alkylating agents exert cytotoxic and, in some cases, chemotherapeutic effects by transferring alkyl groups to DNA, thereby damaging DNA and interfering with DNA replication and cell division.

• Dher2 vaccine+as15 adjuvant - A cancer vaccine consisting of a truncated recombinant HER2/neu peptide (dHER2) combined with the immunoadjuvant AS15 with potential immunostimulatory and antineoplastic activities. Upon administration, dHER2+AS15 vaccine may stimulate the host immune response to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells that overexpress the HER2/neu protein, resulting in tumor cell lysis. The tumor-associated antigen (TAA) HER2/neu is often overexpressed by a variety of tumor cell types; dHER2 includes amino acids 1-645 or 1-653 of the extracellular domain (ECD) and an immunogenic carboxyl terminal autophosphorylation portion of the intracellular domain (ICD). AS15 is an adjuvant formulation that contains the adjuvant systems AS01B and AS07A; AS01 B is composed of liposomes containing 3D-MPL and QS21 and AS07A is composed of the synthetic oligodeoxynucleotide (ODN) Toll-like receptor-9 (TLR9) agonist CpG 7909.

• Dianhydrogalactitol - A bifunctional hexitol derivative with potential antineoplastic activity. Dianhydrogalactitol alkylates and cross-links DNA via an epoxide group during all phases of the cell cycle, resulting in disruption of DNA function and cell cycle arrest.

• Diarylsulfonylurea compound ilx-295501 - ILX-295501 is a novel sulfonylurea compound that has demonstrated in-vivo antitumor activity against a broad spectrum of solid tumors.

• Diazepinomicin - A potent inhibitor of the RAS/RAF/MAPK signaling pathway with potential antineoplastic activity. Diazepinomicin binds to and inhibits Ras kinase, thereby preventing the phosphorylation and activation of proteins downstream of the Ras signal transduction pathway, including serine/threonine kinase RAF (BRAF) and extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK-2), that play a crucial role in regulating cell growth and survival. Diazepinomicin also selectively binds to the peripheral benzodiazepine receptor (BZRP), a receptor highly expressed in certain cancer cells, thus inducing cell cycle arrest and apoptosis in BZRP-expressing cells. In addition, diazepinomicin is able to cross the blood-brain barrier, thereby reaching therapeutic concentrations in the brain.

• Diaziquone - A water-soluble, synthetic aziridinylbenzoquinone with potential antineoplastic activity. Bioactivation of aziridinylbenzoquinone RH1 occurs through the two-electron reduction of the quinone to the hydroquinone by the two-electron quinone reductase DT-diaphorase (DTD). The resultant hydroquinone selectively alkylates and cross-links DNA at the 5'-GNC-3' sequence, inihibiting DNA replication, inducing apoptosis, and inhibiting tumor cell proliferation. DTD is over-expressed in many tumors relative to normal tissue, including lung, colon, breast and liver tumors.

• Diazooxonorleucine - An L-glutamine diazo analogue amino acid antibiotic isolated from a species of the bacterial genus Streptomyces with potential antineoplastic activity. Diazooxonorleucine inhibits several glutamine-dependent biosynthetic pathways involved in the syntheses of D-glucosamine phosphate, purines and pyrimidines. This agent inhibits phosphate-activated glutaminase, a key enzyme for the synthesis of releasable glutamine, depleting cells of this essential amino acid and reducing their capacity to proliferate.

• Dibrospidium chloride - A dispirotripiperazine derivative and alkylating agent with potential antineoplastic and anti-inflammatory activities. Dibrospidium chloride has been examined for the treatment of bone cancer.

• Dichloroallyl lawsone - A triazine derivative with antineoplastic activity. Dichloroallyl lawsone inhibits mitochondrial dihydroorotate dehydrogenase (DHOD), an enzyme that catalyzes the only redox step in de novo pyrimidine biosynthesis, and nucleotide (RNA and DNA) biosynthesis.

• Dicycloplatin - A third-generation, supramolecular platinum-based compound composed of carboplatin linked, by a strong hydrogen bond, to 1,1-cyclobutane dicarboxylate (CBDCA), with potential antineoplastic activity. Although the exact mechanism of action has yet to be fully elucidated, dicycloplatin appears to have a mechanism of action similar to that of other platinum-based compounds, which involves both DNA binding and the formation of DNA crosslinks. This mechanism results in the induction of apoptosis and cell growth inhibition. Compared to carboplatin alone, dicycloplatin shows enhanced solubility and stability in aqueous solution and appears to have a more favorable toxicity profile.

• Dienogest - An orally-active, semisynthetic, fourth generation, nonethinylated progestogen with antiproliferative, antiandrogenic, anti-inflammatory and antiangiogenic activities that is used in hormone therapy and as a female contraceptive. Upon oral administration, dienogest binds intracellular progesterone receptors which then translocate to the nucleus where the drug-receptor complex interacts with progesterone response elements, thus altering the expression of target genes. Dienogest reduces the production of estradiol, prevents ovulation and alters the cervical mucus and endometrium. In addition, dienogest appears to suppress the expression of cell cycle regulator cyclin D1. Altogether, this may prevent the growth of endometrial epithelial cells and may reduce symptoms associated with leiomyoma.

• Diethylnorspermine - A synthetic bis-ethyl analogue of spermine with potential antineoplastic activity. N(1),N(11)-bis(ethyl)norspermine (DENSPM), a N-terminally alkylated tetraamine and polyamine mimetics, disrupts polyamine pool homeostasis by modulating the activities of the biosynthetic enzymes, ornithine decarboxylase (ODC), and S-adenosylmethionine decarboxylase (AdoMetDC). This agent also reduces polyamine concentrations through the induction of the catabolic enzyme spermidine/spermine N1-acetyltransferase 1 (SSAT). Polyamines, an integral part of the DNA helix structure, play a critical role in cell division, differentiation and membrane function. Disruption of normal polyamine concentrations by DENSPM may lead to cell growth inhibition.

• Digitoxin - A lipid soluble cardiac glycoside that inhibits the plasma membrane sodium potassium ATPase, leading to increased intracellular sodium and calcium levels and decreased intracellular potassium levels. In studies increased intracellular calcium precedes cell death and decreased intracellular potassium increase caspase activation and DNA fragmentation, causing apoptosis and inhibition of cancer cell growth. (NCI)

• Digoxin - A cardiac glycoside. Digoxin inhibits the sodium potassium adenosine triphosphatase (ATPase) pump, thereby increasing intracellular calcium and enhancing cardiac contractility. This agent also acts directly on the atrioventricular node to suppress conduction, thereby slowing conduction velocity. Apparently due to its effects on intracellular calcium concentrations, digoxin induces apoptosis of tumor cells via a pathway involving mitochondrial cytochrome c and caspases 8 and 3.

• Dihydro-5-azacytidine - A synthetic nucleoside analogue of deoxycytidine. Dihydro-5-azacytidine inhibits DNA methyltransferase, thereby interfering with abnormal DNA methylation patterns that are associated with genetic instability in some tumor cells. Inhibition of this enzyme may restore expression of tumor-suppressor genes and result in antitumor activity.

• Dihydrolenperone - A butyrophenone that has been investigated for antineoplastic activity.

• Dihydroorotate dehydrogenase inhibitor bay2402234 - An orally available inhibitor of dihydroorotate dehydrogenase (DHODH), with potential antineoplastic activity. Upon administration, BAY2402234 specifically targets, binds to and prevents the activation of DHODH, thereby preventing the fourth enzymatic step in de novo pyrimidine synthesis. This prevents uridine monophosphate (UMP) formation, DNA synthesis, cell division and cellular proliferation, causes reactive oxygen species (ROS) production, enables differentiation and induces apoptosis in susceptible tumor cells. DHODH, a mitochondrial enzyme, catalyzes the conversion of dihydroorotate (DHO) to orotate in the endogenous synthesis of UMP.

• Diindolylmethane - A phytonutrient and plant indole found in cruciferous vegetables including broccoli, Brussels sprouts, cabbage, cauliflower and kale, with potential anti-androgenic and antineoplastic activities. As a dimer of indole-3-carbinol, diindolylmethane (DIM) promotes beneficial estrogen metabolism in both sexes by reducing the levels of 16-hydroxy estrogen metabolites and increasing the formation of 2-hydroxy estrogen metabolites, resulting in increased antioxidant activity. Although this agent induces apoptosis in tumor cells in vitro, the exact mechanism by which DIM exhibits its antineoplastic activity in vivo is unknown.

• Di-leu16-il2 immunocytokine - A recombinant fusion protein consisting of de-immunized and humanized anti-CD20 monoclonal antibody Leu16 fused to human cytokine interleukin-2 (IL2) with potential antineoplastic activity. The antibody moiety of DI-Leu16-IL2 immunocytokine binds to tumor cells expressing the CD20 antigen, which may result in an antibody-dependent cell-mediated cytotoxicity (ADCC) towards CD20-expressing tumor cells; the localized IL2 moiety of this fusion protein may stimulate natural killer (NK) and T-lymphocyte mediated immune responses, enhancing the ADCC response. De-immunization involves the modification of potential helper T cell epitopes that bind to MHC class II molecules; humanization involves combining recombinant murine variable (V) regions with human immunoglobulin light and heavy chain constant regions. CD20 antigen, a hydrophobic transmembrane protein located on normal pre-B and mature B lymphocytes, is overexpressed by various cancer cell types.

• Dilpacimab - A dual-specific, tetravalent immunoglobulin (Ig) G-like molecule targeting two as of yet not publicly known targets, with potential antineoplastic activity. The target-binding variable domains of two monoclonal antibodies, which are not publicly known, are combined, via linkers, to create the tetravalent, dual-targeting single agent ABT-165. Upon administration of dual variable domain immunoglobulin (DVD-Ig) ABT-165, the target-binding variable domains specifically recognize and simultaneously bind to their two antigens expressed on tumor cells. This may both prevent antigen-mediated signaling and lead to an inhibition of cellular proliferation in susceptible tumor cells. The antigen targets are overexpressed on certain tumor cell types. The DVD-Ig may have enhanced physicochemical and pharmacokinetic properties as compared to their antibody counterparts.

• Dimethylmyleran - An aliphatic analogue of busulfan with potential antineoplastic activity. As an alkylating agent, dimethylbusulfan induces neutropenia and has been shown to exhibit antitumor effects in some animal models. Alkylating agents exert cytotoxic and chemotherapeutic effects by transferring alkyl groups to DNA, thereby damaging DNA and interfering with DNA synthesis and cell division.

• Dinaciclib - A pyrazolo[1,5-a]pyrimidine with potential antineoplastic activity. Dinaciclib selectively inhibits cyclin dependent kinases CDK1, CDK2, CDK5, and CDK9; inhibition of CDK1 and CDK2 may result in cell cycle repression and tumor cell apoptosis.

• Dinitrophenyl-modified autologous renal cell carcinoma tumor cell vaccine - A cancer vaccine consisting of autologous renal cell carcinoma (RCC) tumor cells modified with the hapten 2,4-dinitrophenol (DNP) with potential immunostimulating and antineoplastic activities. Administration of DNP-modified autologous renal cell carcinoma tumor cell vaccine may induce a cytotoxic T-lymphocyte (CTL) response against renal cell carcinoma tumor cells. DNP conjugation may enhance the immunogenicity of weakly immunogenic antigens.

• Dinutuximab - A chimeric mouse/human monoclonal antibody with potential antineoplastic activity. Dinutuximab binds to the ganglioside GD2 and induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity against GD2-expressing tumor cells. GD2 is overexpressed in malignant melanoma, neuroblastoma, osteosarcoma, and small cell carcinoma of the lung.

• Dioscorea nipponica makino extract dne3 - An extract of the plant Dioscorea nipponica Makino and inhibitor of both the serine/threonine protein kinase Akt (protein kinase B) and members of the phosphatidylinositol 3-kinase (PI3K) family of lipid kinases, with potential antineoplastic and anti-metastatic activities. Dioscorea nipponica Makino extracted with ethyl acetate (DNE3) binds to and inhibits PI3K and Akt. This inhibits PI3K/Akt-mediated signaling and prevents both growth and survival of PI3K/Akt-overexpressing tumor cells. In addition, DNE3 increases the expression of tissue inhibitor of metalloproteinase-2 (TIMP-2), inhibits the secretion of matrix metalloproteinases (MMPs), primarily MMP-2 and MMP-9, and inhibits the serine protease urokinase (urokinase-type plasminogen activator; u-PA). This inhibits tumor cell invasion, migration, motility, and adhesion. This agent also inhibits the activation of both cAMP response element-binding (CREB) and activating protein-1 (AP-1), and increases the expression of IkappaB (IkB), which inhibits the activation of nuclear factor-kappa B (NF-kB). These processes further contribute to this agent's anti-tumor potential in susceptible tumor cells.

• Diphtheria toxin fragment-interleukin-2 fusion protein e7777 - A cytotoxic recombinant fusion protein consisting of the human cytokine interleukin-2 (IL-2) fused to diphtheria toxin fragments A and B, containing both the catalytic and translocation domains, with potential antineoplastic activity. Upon administration, the IL-2 moiety of diphtheria toxin fragment-IL-2 fusion protein E7777 binds to IL-2 receptors. After internalization by IL-2 receptor-expressing cells via endocytosis, the agent is proteolytically cleaved. This releases the catalytic domain of the toxin moiety, which catalyzes the transfer of the ADP-ribose moiety of NAD to a diphthamide residue of elongation factor 2 (EF-2). This covalent modification inactivates EF-2 and disrupts polypeptide chain elongation, resulting in an inhibition of translation and cell death. E7777 has the same amino acid sequence as denileukin diftitox (DD), but has an increased purity profile and an increased percentage of monomeric, active protein, which improves its efficacy.

• Distilled water - An ultra-pure form of water with potential antineoplastic activity. Derived by boiling impure water and condensing the resultant steam in a sterile container, distilled water has been shown to kill bladder cancer cells in vitro through osmotic lysis (cytolysis)

• Ditiocarb - A sulfhydryl-containing carbamate that is the primary in vivo metabolite of disulfiram. Diethyldithiocarbamate chelates zinc, thereby inhibiting metalloproteinases, thereby preventing the degradation of the extracellular matrix and inhibiting an initial step in cancer metastasis and angiogenesis. A known inhibitor of superoxide dismutase, this agent can either potentiate or protect against cell oxidative damage caused by ionizing radiation, depending on the time of administration.

• Dkk1-neutralizing monoclonal antibody dkn-01 - A humanized monoclonal antibody directed against Wnt antagonist Dickkopf-1 (DKK1) with potential anti-osteolytic activity. DKK1-neutralizing monoclonal antibody DKN-01 binds to and inhibits DKK1, which restores Wnt pathway signaling. Reactivation of the Wnt signaling pathway may result in the differentiation and activation of osteoblasts within the bone matrix and the reversal of tumor-induced osteolytic disease. Elevated levels of circulating DKK1, a potent Wnt signaling pathway antagonist, is associated with a number of neoplastic diseases.

• Dkk1-neutralizing monoclonal antibody dkn-01 - A human monoclonal antibody directed against the WNT antagonist dickkopf homolog 1 (DKK1), with potential anti-osteolytic activity. DKK1-neutralizing Monoclonal Antibody DKN-01 binds to and inhibits DKK1, thereby restoring signaling through the WNT pathway, which may result in osteoblast differentiation and activation within the bone matrix and the reversal of tumor-induced osteolytic disease. DKK1, overexpressed by myeloma cells, is an inhibitor of the WNT signaling pathway and prevents the mediated formation of bone.

• Dlk1/epha2/hbb/nrp1/rgs5/tem1 peptide-pulsed alpha-type-1 polarized dendritic cell vaccine - A cell based cancer vaccine composed of mature polarized dendritic cells (alphaDC1) pulsed with six human leukocyte antigen (HLA)-A2-presented tumor blood vessel antigen (TBVA)-derived peptides, with potential immunostimulatory and antineoplastic activities. Dendritic cells (DCs) were treated with a "type-1 polarizing cytokine cocktail", including interleukin-1beta, tumor necrosis factor alpha (TNF-a), interferon-alpha (IFN-a), IFN-gamma and polyinosinic:polycytidylic acid (pI:C) to produce mature alpha type-1 polarized DCs (alphaDC1) that are capable of producing high levels of interleukin-12p70 (IL-12p70). The alphaDC1 are subsequently pulsed with TBVA-derived peptides, including delta-like homologue 1 (DLK1) 310-318, EPH receptor A2 (EPHA2) 883-891, beta-globin (HBB) 31-39, neuropilin-1 (NRP1) 433-441, regulator of G-protein signaling 5 (RGS5) 5-13 and tumor endothelial marker 1 (TEM1) 691-700. Upon administration, these DCs are able to induce a potent cytotoxic T-lymphocyte (CTL) response against the TBVAs expressed on tumor-associated stromal cells, which results in stromal cell lysis and inhibition of angiogenesis. Disrupting the surrounding tumor vasculature inhibits tumor cell growth and survival. alphaDC1 are able to induce a potent tumor antigen-specific CTL response due to their high co-stimulatory activity and the secretion of anti-cancer cytokines, such as IL-12p70.

• Dm4-conjugated anti-cripto monoclonal antibody biib015 - A humanized IgG1 monoclonal antibody directed against the cell surface-associated protein Cripto and conjugated to the maytansinoid DM4 with potential antineoplastic activity. The monoclonal antibody moiety of DM4-conjugated anti-Cripto monoclonal antibody BIIB015 binds to the tumor associated antigen (TAA) Cripto; upon internalization, the DM4 moiety binds to tubulin and disrupts microtubule assembly/disassembly dynamics, resulting in inhibition of cell division and cell growth of Cripto-expressing tumor cells. Constitutively expressed during embryogenesis, Cripto belongs to the EGF-CFC family of growth factor-like molecules and plays a key role in signaling pathways of certain transforming growth factor-beta superfamily members; as a TAA, Cripto is overexpressed in carcinomas such as those of the breast, ovary, stomach, lung, and pancreas while its expression is absent in normal tissues.

• Dm-choc-pen - A cholesterol carbonate derivative of 4-demethylpenclomedine (DM-PEN) with potential antineoplastic alkylating activity. Upon intravenous administration of 4-demethylcholesteryloxycarbonylpenclomedine, the carbonium moiety binds to and alkylates DNA at the N7 guanine position, thereby causing DNA crosslinks. This prevents DNA replication, inhibits cellular proliferation and triggers apoptosis. In addition, due to its lipophilic cholesteryl moiety this agent is able to cross the blood brain barrier (BBB) and therefore can be given intravenously compared to other alkylating agents that need to be given intra-cranially.

• D-methionine formulation mrx-1024 - A proprietary oral formulation of D-methionine with antioxidant and antimucositis activities. D-methionine formulation MRX-1024 may selectively protect the oral mucosa from the toxic effects of chemotherapy and radiation therapy without compromising antitumor activity. D-methionine may be converted into the L- isomer in vivo, particularly in instances of L-methionine deprivation; both isomers have antioxidant activity which may be due, in part, to their sulfur moieties and chelating properties. L-methionine, an essential amino acid, also may help to maintain the ratio of reduced glutathione to oxidized glutathione in cells undergoing oxidative stress and may provide a source of L-cysteine for glutathione synthesis.

• Dna interference oligonucleotide pnt2258 - A liposomal formulation of the 24-mer oligonucleotide PNT100, with potential antineoplastic activity. PNT2258 targets and complements to untranscribed DNA sequence upstream of BCL2 promoters, thereby interfering with DNA replication and transcription of the BCL2 gene. This may promote and restore the apoptotic pathway in BCL2-overexpressing tumor cells. BCL2, an anti-apoptotic protein, is overexpressed in a wide variety of tumors.

• Dna minor groove binding agent sg2000 - A sequence-selective pyrrolobenzodiazepine (PBD) dimer with potential antineoplastic activity. Following intravenous administration, DNA minor groove binding agent SG2000 preferentially and covalently binds to purine-GATC-pyrimidine sequences, with the imine/carbinolamine moieties of SG2000 binding to the N2 positions of guanines on opposite strands of DNA. This induces interstrand cross-links and inhibits both DNA replication and gene transcription, which lead to the inhibition of cell growth. With a preference for binding to purine-GATC-pyrimidine sequences, SG2000 adducts do not appear to be susceptible to p53-mediated DNA excision repair.

• Dna plasmid-encoding interleukin-12 ino-9012/psa/psma dna plasmids ino-5150 formulation ino-5151 - A DNA-based combined formulation composed of INO-5150, DNA plasmids encoding the tumor-associated antigens (TAAs) prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA), and INO-9012, a plasmid DNA vaccine encoding the immune activator and pro-inflammatory cytokine human interleukin-12 (IL-12), with potential immunoactivating and antineoplastic activities. Upon intramuscular delivery of INO-5151 and electroporation of the PSA/PSMA DNA plasmid INO-5150, PSA and PSMA are translated in cells and elicit a cytotoxic T-lymphocyte (CTL) response against cancer cells expressing PSA and PSMA, resulting in tumor cell lysis. Upon electroporation of the DNA plasmid encoding IL-12 INO-9012, IL-12 is translated in cells and the expressed IL-12 activates the immune system by promoting the activation of natural killer cells (NK cells), inducing secretion of interferon-gamma (IFN-g) and promoting CTL responses against tumor cells. This boosts the immune response and results in increased CTL-mediated tumor cell death as compared with the administration of INO-5150 alone. PSA and PSMA are overexpressed on a variety of cancer cell types.

• Dna plasmid-encoding interleukin-12/hpv dna plasmids therapeutic vaccine medi0457 - A DNA-based combination immunotherapeutic, MEDI0457, composed of VGX-3100, a preparation of DNA plasmids encoding the E6 and E7 genes of human papillomavirus (HPV) subtypes 16 and 18, combined with INO-9012, a DNA plasmid encoding the immune activator and pro-inflammatory cytokine human interleukin-12 (IL-12) with potential immunoactivating and antineoplastic activities. Upon intramuscular delivery by electroporation of VGX-3100, the HPV E6 and E7 proteins are translated in cells and elicit a cytotoxic T-lymphocyte (CTL) response against cancer cells expressing the E6 and E7 antigens, resulting in tumor cell lysis. HPV type 16 and HPV type 18 are associated with the development of certain types of cancer. Upon intramuscular delivery by electroporation of INO-9012, IL-12 is expressed and activates the immune system by promoting the activation of natural killer cells (NK cells), inducing secretion of interferon-gamma (IFN-g) and promoting CTL responses against tumor cells. This boosts the immune response and results in increased CTL-mediated tumor cell death as compared with the administration of VGX-3100 alone.

• Dna vaccine vb10.16 - A therapeutic DNA vaccine composed of three parts, one encodes the E6/E7 fusion protein of human papillomavirus (HPV) type 16 (HPV16), the second is a dimerization entity and the third part encodes a protein that specifically binds to antigen presenting cells (APCs), with potential immunostimulating and antineoplastic activities. Upon intramuscular administration, the DNA vaccine VB10.16 expresses HPV16 E6/7 and a protein that targets receptors on APCs. Upon binding to APCs and subsequent internalization, the APCs mature and the HPV16 E6/7 antigenic protein is presented by the APCs. This attracts and stimulates B-lymphocytes, CD4-positive T-lymphocytes and elicits a cytotoxic T-lymphocyte (CTL) response against cancer cells expressing HPV16-associated E6 and E7 oncoproteins, which result in tumor cell lysis. HPV16 E6/7, a viral antigen, plays a key role in the development of certain types of cancer.

• Dna vector ppra-psm vaccine - A cancer vaccine consisting of a DNA plasmid encoding epitopes of the human preferential antigen of melanoma (PRAME) and the prostate specific membrane antigen (PSMA) with potential immunostimulating activity. Upon direct administration of this vaccine into lymph nodes, peptides expressed by DNA plasmid vector pPRA-PSM may activate the immune system, resulting in a cytotoxic T-lymphocyte (CTL) response against PRAME- and PSMA-expressing cells. PRAME and PSMA are tumor associated antigens upregulated in a number of cancer cell types. As part of the MKC1106-PP regimen exploiting the 'prime-boost strategy', this plasmid is responsible for priming the immune response and is used in conjunction with a peptide vaccine consisting of PRAME and PSMA that boosts the immune system against PRAME- and PSMA-expressing tumor cells.

• Dna-dependent protein kinase inhibitor vx-984 - An ATP-competitive inhibitor of the catalytic subunit of DNA-dependent protein kinase (DNA-PK), with potential sensitizing and enhancing activities for both chemo- and radiotherapies. Upon administration, DNA-PK inhibitor VX-984 binds to and inhibits the catalytic subunit of DNA-PK, thereby interfering with the non-homologous end joining (NHEJ) process and preventing repair of DNA double strand breaks (DSBs) caused by ionizing radiation or chemotherapeutic treatment. This increases chemo- and radiotherapy cytotoxicity and leads to enhanced tumor cell death. The enhanced ability of tumor cells to repair DSBs plays a major role in the resistance of tumor cells to chemo- and radiotherapy; DNA-PK plays a key role in the NHEJ pathway and DSB repair.

• Dna-pk inhibitor azd7648 - An orally bioavailable ATP-competitive inhibitor of DNA-dependent protein kinase (DNA-PK), with potential chemo/radiosensitizing and antineoplastic activites. Upon oral administration, DNA-PK inhibitor AZD7648 selectively targets, binds to and inhibits the activity of DNA-PK, thereby interfering with the non-homologous end joining (NHEJ) process and preventing repair of DNA double strand breaks (DSBs) caused by ionizing radiation or chemotherapeutic treatment. This increases chemo- and radiotherapy cytotoxicity leading to enhanced tumor cell death. AZD7648 may also increase the effect of poly(ADP-ribose) polymerase (PARP) inhibitors and may work as a monotherapy in tumors with high endogenous levels of DNA damage resulting from defects in other DNA repair pathways. The enhanced ability of tumor cells to repair DSBs plays a major role in the resistance of tumor cells to chemo- and radiotherapy. DNA-PK plays a key role in the NHEJ pathway and DSB repair.

• Dna-pk/pi3k-delta inhibitor br101801 - An orally bioavailable inhibitor of phosphoinositide 3-kinase delta (PI3-kinase subunit delta; PI3K-delta; PI3Kdelta) and DNA-dependent protein kinase (DNA-PK), with potential antineoplastic and immunomodulating activities. Upon oral administration, the DNA-PK/PI3K-delta inhibitor BR101801 inhibits the activity of both PI3K-delta and DNA-PK. This prevents PI3K-mediated signaling pathways and may lead to the inhibition of cancer cell growth in PI3K-overexpressing tumor cells. Specifically, since PI3K regulates c-myc expression, inhibition of PI3K signaling may lead to a decrease in proliferation of c-myc-expressing tumor cells. Also, by inhibiting the activity of DNA-PK, this agent interferes with the non-homologous end joining (NHEJ) process and prevents the repair of DNA double strand breaks (DSBs) caused by ionizing radiation or chemotherapeutic treatment. This increases chemo- and radiotherapy cytotoxicity by inhibiting the ability of tumor cells to repair damaged DNA. The PI3K pathway is upregulated in a variety of tumors and plays an important role in regulating cancer cell proliferation, growth, and survival. DNA-PK is activated upon DNA damage and plays a key role in repairing double-stranded DNA breaks. The enhanced ability of tumor cells to repair DSBs plays a major role in the resistance of tumor cells to chemo- and radiotherapy. In addition, BR101801 is able to decrease Tregs and increase CD8 lymphocytes.

• Dna-pk/tor kinase inhibitor cc-115 - A dual inhibitor of DNA-dependent protein kinase (DNA-PK) and mammalian target of rapamycin (mTOR), with potential antineoplastic activity. CC-115 binds to and inhibits the activity of DNA-PK and both raptor-mTOR (TOR complex 1 or TORC1) and rictor-mTOR (TOR complex 2 or TORC2), which may lead to a reduction in cellular proliferation of cancer cells expressing DNA-PK and TOR. DNA-PK, a serine/threonine kinase and a member of the PI3K-related kinase subfamily of protein kinases, is activated upon DNA damage and plays a key role in repairing double-stranded DNA breaks via the DNA nonhomologous end joining (NHEJ) pathway; mTOR, a serine/threonine kinase that is upregulated in a variety of tumors, plays an important role downstream in the PI3K/Akt/mTOR signaling pathway.

• Dnmt1 inhibitor ntx-301 - An orally bioavailable inhibitor of human DNA methyltransferase 1 (DNMT1), with potential antineoplastic activity. Upon oral administration, DNMT1 inhibitor NTX-301 targets ad binds to DNMT1, thereby inhibiting the activity of DNMT1. This may prevent DNA methylation, induce DNA hypomethylation, and activate tumor suppressor genes silenced by hypermethylation. This may inhibit tumor cell proliferation. DNMT1, a member of the DNA methyltransferase (DNMT) family, plays an important role in maintaining the DNA methylation pattern. Dysregulation of DNMT1 has been associated with a number of cancers.

• Dnmt1 mixed-backbone antisense oligonucleotide mg 98 - A second-generation, mixed-backbone, phosphorothioate antisense oligonucleotide (ODN) with potential antitumor activity. MG 98 is a highly specific inhibitor of translation of the mRNA for human DNA (cytosine-5-)-methyltransferase 1 (DNMT1), hybridizing to the 3' un-translated region of DNMT1 mRNA. The silencing of DNMT1 translation by MG 98 may result in the prevention or reversal of abnormal methylation of tumor suppressor genes and ultimately in tumor growth inhibition or tumor regression.

• Dnr-expressing nasopharyngeal carcinoma-specific cytotoxic t-lymphocytes - A preparation of autologous, dominant-negative receptor (DNR)-expressing nasopharyngeal carcinoma (NPC)-specific cytotoxic T-lymphocytes (CTLs), with potential antineoplastic activity. The DNR-expressing NPC-specific CTLs specifically target Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1), latent membrane proteins (LMP) and BamHIA rightward frame 1 (BARF1), and are transduced with a retroviral vector expressing DNR, a dominant-negative form of the transforming growth factor beta (TGFb) receptor, which blocks TGF-beta-mediated signaling. Upon administration, the CTLs recognize and target NPC cells, which may result in both CTL-mediated cell lysis and the inhibition of tumor cell proliferation. Tumor-expressed TGF-beta inhibits T-lymphocyte activation and expansion; resistance to TGF-beta allows for optimal CTL activity. EBV infection plays a key role in NPC tumorigenesis.

• Docetaxel - A semi-synthetic, second-generation taxane derived from a compound found in the European yew tree, Taxus baccata. Docetaxel displays potent and broad antineoplastic properties; it binds to and stabilizes tubulin, thereby inhibiting microtubule disassembly which results in cell- cycle arrest at the G2/M phase and cell death. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and displays immunomodulatory and pro-inflammatory properties by inducing various mediators of the inflammatory response. Docetaxel has been studied for use as a radiation-sensitizing agent.

• Docetaxel anhydrous - The anhydrous form of docetaxel, a semisynthetic side-chain analogue of paclitaxel with antineoplastic property. Docetaxel binds specifically to the beta-tubulin subunit of microtubules and thereby antagonizes the disassembly of the microtubule proteins. This results in the persistence of aberrant microtubule structures and results in cell-cycle arrest and subsequent cell death.

• Docetaxel emulsion anx-514 - An injectable emulsion formulation containing the taxane docetaxel, a semisynthetic analogue of paclitaxel, with antineoplastic activity. Docetaxel binds specifically to the beta-tubulin subunit of the microtubule, stabilizing tubulin and inhibiting microtubule disassembly, which results in cell-cycle arrest at the G2/M phase and cell death. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and induces various mediators of the inflammatory response. Docetaxel emulsion ANX-514 is formulated without polysorbate 80 or other detergents in order to reduce the incidence and severity of hypersensitivity reactions. In addition, the exclusion of polysorbate 80 in this formulation precludes foaming during the preparation process, thus facilitating preparation and administration.

• Docetaxel formulation ckd-810 - An injectable formulation containing the taxane docetaxel, a semisynthetic analogue of paclitaxel, with antineoplastic activity. Docetaxel binds specifically to the beta-tubulin subunit of the microtubule, stabilizing tubulin and inhibiting microtubule disassembly, which results in cell-cycle arrest at the G2/M phase and cell death. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and induces various mediators of the inflammatory response.

• Docetaxel lipid microspheres - A lipid microsphere (LM)-based formulation containing the poorly water soluble taxane docetaxel, a semi-synthetic analogue of paclitaxel, with antineoplastic activity. Docetaxel binds specifically to the beta-tubulin subunit of the microtubule, stabilizing tubulin and inhibiting microtubule disassembly, which causes cell cycle arrest at the G2/M phase and leads to cell death. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and induces various mediators of the inflammatory response. Compared to docetaxel alone, the LM formulation may enhance stability, improve efficacy and may reduce toxicity; this formulation does not contain toxic detergents needed to solubilize docetaxel which further improves its side effect profile.

• Docetaxel nanoparticle cpc634 - A polymeric nanoparticle (PNP) formulation containing the poorly water-soluble taxane docetaxel, a semi-synthetic analogue of paclitaxel, with antineoplastic activity. Upon intravenous administration of the docetaxel nanoparticle CPC634, the nanoparticles are able to accumulate at the tumor site due to the unique characteristics of the tumor's vasculature, while avoiding normal, healthy tissue. In turn, docetaxel is released locally at the target tumor site, binds specifically to the beta-tubulin subunit of the microtubule, stabilizing tubulin and inhibiting microtubule disassembly, which results in cell-cycle arrest at the G2/M phase, thereby preventing cell proliferation. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and induces various mediators of the inflammatory response. Compared to docetaxel alone, this formulation may enhance stability and improve delivery, thereby increasing docetaxel's efficacy while avoiding systemic exposure, which minimizes its toxicity.

• Docetaxel polymeric micelles - A nanoparticle-based formulation consisting of polymeric micelles (PMs), made with poly(N-vinylpyrrolidone)-block-poly(D,L-lactide) (PVP-b-PDLLA) block polymers, encapsulating the taxane docetaxel, a semi-synthetic analogue of paclitaxel, with potential antineoplastic activity. Upon intravenous administration of the docetaxel PMs, the nanoparticles are able to accumulate at the tumor site due to the unique characteristics of the tumor's vasculature, while avoiding normal, healthy tissue. In turn, docetaxel is released locally at the target tumor site where it binds specifically to the beta-tubulin subunit of the microtubule, thereby stabilizing tubulin and inhibiting microtubule disassembly. This results in cell-cycle arrest at the G2/M phase, thereby preventing cell proliferation. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and induces various mediators of the inflammatory response. Compared to docetaxel alone, this formulation may enhance stability and improve delivery, thereby increasing docetaxel's efficacy while avoiding systemic exposure, which minimizes its toxicity.

• Docetaxel/ritonavir - An orally bioavailable combination agent containing docetaxel, a second generation taxane, and ritonavir, a cytochrome P450 (CYP) 3A4 inhibitor, with potential enhanced antineoplastic activity. Docetaxel binds to and stabilizes tubulin, thereby inhibiting microtubule disassembly which results in cell-cycle arrest at the G2/M phase and cell death. Docetaxel is metabolized by CYP3A4 enzymes which is inhibited by the presence of ritonavir. This increases the plasma concentration of docetaxel and may increase docetaxel's efficacy.

• Docetaxel-loaded nanopharmaceutical crlx301 - A nanoparticle-based formulation containing the poorly water-soluble, second-generation taxane analog docetaxel, with antineoplastic activity. Upon intravenous administration of the docetaxel-loaded nanopharmaceutical CRLX301, the nanoparticles are able to accumulate at the tumor site due to the unique characteristics of the tumor's vasculature, while avoiding normal, healthy tissue. In turn, CRLX301 is taken up by the tumor cell via macropinocytosis. Subsequently, docetaxel is slowly released into the cytoplasm where it binds to and stabilizes the beta-subunit of tubulin, thereby stabilizing microtubules and inhibiting microtubule disassembly. This prevents mitosis and results in cell death. Compared to the administration of docetaxel alone, this formulation is able to increase docetaxel's efficacy while avoiding systemic exposure, which minimizes its toxicity.

• Docetaxel-pnp - A polymeric nanoparticle (PNP) formulation containing the taxane docetaxel, a semi-synthetic analogue of paclitaxel, with antineoplastic activity. Docetaxel binds specifically to the beta-tubulin subunit of the microtubule, stabilizing tubulin and inhibiting microtubule disassembly, which results in cell-cycle arrest at the G2/M phase, preventing cell proliferation. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and induces various mediators of the inflammatory response. Compared to docetaxel alone, the PNP formulation may enhance stability and improve delivery.

• Dociparstat sodium - A heparin derivative in which the 2-O and 3-O sulfate groups of heparin are removed and that lacks anticoagulant activity, with potential anti-inflammatory, immodulatory and antineoplastic activities. Upon administration, dociparstat sodium binds to both chemokine stromal cell-derived factor 1 (SDF-1 or CXCL12) and CXC chemokine receptor 4 (CXCR4). This prevents the interaction of CXCL12 with CXCR4, blocks CXCR4 activation, and may result in decreased proliferation and migration in CXCR4-overexpressing tumor cells. In addition, inhibition of CXCL12/CXCR4 interaction may induce mobilization of hematopoietic cells from the bone marrow into the blood. In addition, dociparstat sodium prevents the interaction of the receptor for advanced glycation end-products (RAGE) with its ligands, including advanced glycation end-products (AGEs), Mac-1(CD11b/CD18), the nuclear pro-inflammatory protein high mobility group box protein-1 (HMGB-1), carboxymethyl lysine-bovine serum albumin (CML-BSA) and members of the S100 calgranulin family. In addition, this agent inhibits the enzymes heparanase, cathepsin G, and human leukocyte elastase, which are involved in inflammation and metastasis. Altogether, this may inhibit tumor cell invasiveness and metastasis. Dociparstat sodium also binds to platelet factor 4 (PF4 or CXCL4) and may prevent PF4's inhibitory effect on platelet production. This may increase platelet production. Unlike heparin, this agent does not induce heparin-induced thrombocytopenia (HIT). RAGE, a receptor belonging to the immunoglobulin superfamily, plays a key role in inflammation and is overexpressed in a variety of cancers. CXCR4 is a chemokine receptor belonging to the G protein-coupled receptor (GPCR) family that plays an important role in chemotaxis, chemoresistance and angiogenesis, and is upregulated in several tumor cell types. The interaction between CXCL12/CXCR4 induces retention of hematopoietic cells in the bone marrow.

• Dolastatin 10 - A pentapeptide originally isolated from the marine mollusk Dolabella auricularia with potential antineoplastic activity. Binding to tubulin, Dolastatin 10 inhibits microtubule assembly, resulting in the formation of tubulin aggregates and inhibition of mitosis. This agent also induces tumor cell apoptosis through a mechanism involving bcl-2, an oncoprotein that is overexpressed in some cancers.

• Dolastatin 15 - A depsipeptide originally isolated from the marine mollusk Dolabella auricularia with potential antineoplastic activity. Less potent than the structurally-related compound dolastatin 10, dolastatin 15 binds weakly to tubulin and blocks microtubule assembly, thereby inhibiting mitosis. Dolastatin 15 also induces tumor cell apoptosis through a mechanism involving bcl-2, an oncoprotein that is overexpressed in some cancers.

• Domatinostat - An orally bioavailable benzamide and inhibitor of human class I histone deacetylases (HDACs) isoenzymes 1, 2 and 3, with potential antineoplastic activity. Domatinostat selectively binds to and inhibits class I HDACs leading to an accumulation of highly acetylated histones. This may result in an induction of chromatin remodeling, the selective transcription of tumor suppressor genes, and the tumor suppressor protein-mediated inhibition of tumor cell division and eventually the induction of tumor cell apoptosis. This may inhibit tumor cell proliferation in susceptible tumor cells. HDACs, upregulated in many tumor types, are a class of enzymes that deacetylate chromatin histone proteins.

• Donafenib - An orally available multikinase inhibitor that targets Raf kinase and various receptor tyrosine kinases (RTKs), with potential antineoplastic activity. Upon oral administration, donafenib binds to and blocks the activity of Raf kinase, and inhibits Raf-mediated signal transduction pathways. This inhibits cell proliferation in Raf-expressing tumor cells. In addition, this agent may inhibit unidentified RTKs, and thus may further block tumor cell proliferation in susceptible tumor cells. Raf, a serine/threonine protein kinase, plays a key role in the Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway. Deregulation of this pathway often results in tumor cell proliferation and survival.

• Donor lymphocytes - A population of lymphocytes from the blood of a donor and administered to a patient who has already received a stem cell transplant from the same donor (Allogeneic Hematopoietic Stem Cell Transplantation). The donor lymphocytes may be able to boost the patient's immune system and kill remaining cancer cells.

• Donor-derived wt1/prame/ny-eso-1/survivin-specific t-lymphocytes - Allogeneic T-lymphocytes specifically reactive to the tumor-associated antigens (TAAs) human Wilms tumor protein-1 (WT1), Preferentially Expressed Antigen in Melanoma (PRAME), the cancer-testis antigen NY-ESO-1, and survivin, with potential antineoplastic activity. Donor derived T-cells are mixed, ex vivo, with protein fragments derived from the TAAs WT1, PRAME, NY-ESO-1, and survivin. Upon intravenous administration, the donor-derived WT1/PRAME/NY-ESO-1/Survivin-specific T-lymphocytes recognize and kill cancer cells expressing these TAAs. WT1, NY-ESO-1, PRAME, and survivin, are expressed on certain tumor cell types and play key role in tumor cell proliferation and survival.

• Dopamine-somatostatin chimeric molecule bim-23a760 - A chimeric molecule directed against dopamine and somatostatin receptors with potential antineoplastic activity. Combining two pharmacological moieties, a somatostatin analogue and a dopamine agonist, dopamine-somatostatin chimeric molecule BIM-23A760 binds with high affinity to dopamine D2 receptor (D2R) and somatostatin receptor subtype 2 (SSTR2), and to a lesser extent to somatostatin receptor subtype 5 (SSTR5). This agent appears to exert its effect mainly by binding to D2R to activate the ERK1/2 and p38 MAPK pathways, thus inducing apoptosis and inhibiting cellular proliferation in non-functioning pituitary adenoma (NFPA) and neuroendocrine tumors. By binding to SSTR2, this agent may inhibit the secretion of growth hormone (GH) by the pituitary gland.

• Dostarlimab - A humanized monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death 1 (PD-1; programmed death-1), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, dostarlimab binds to and inhibits PD-1 and its downstream signaling pathways. This may restore immune function through the activation of T-cells. PD-1, a transmembrane protein in the Ig superfamily expressed on T-cells, functions as an immune checkpoint protein that negatively regulates T-cell activation and T-cell-mediated immune responses when activated by its ligands programmed cell death receptor ligand 1 (PD-L1) or 2 (PD-L2); it plays an important role in tumor evasion from host immunity.

• Dotap:cholesterol-fus1 liposome complex - A formulation composed of DOTAP:cholesterol liposomal nanoparticles complexed with a plasmid expression cassette encoding human FUS1 protein, with potential antineoplastic activity. Upon administration, DOTAP:chol-Fus1 liposome complex accumulates mainly in the lungs and particularly in cancer cells. Upon transfer of the Fus1 gene into tumor cells, the expression of Fus1 may induce tumor cell apoptosis and suppress tumor cell proliferation. Fus1, a potent tumor-suppressor protein, is present in normal, healthy cells but often absent in certain cancer cells. DOTAP:cholesterol liposome is composed of cationic lipid dioleoyl-trimethylammonium propane (DOTAP) and cholesterol at a molar ratio of 1:1.

• Dovitinib - A benzimidazole-quinolinone compound and receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Dovitinib binds to and inhibits the phosphorylation of type III-V RTKs, such as vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) that promote tumor cell proliferation and survival in certain cancer cells. In addition, this agent also inhibits other members of the RTK superfamily, including fibroblast growth factor receptor 1 and 3, FMS-like tyrosine kinase 3, stem cell factor receptor (c-KIT), and colony stimulating factor receptor 1. This may further lead to a reduction of cellular proliferation and angiogenesis, and an induction of tumor cell apoptosis.

• Dovitinib lactate - The orally bioavailable lactate salt of a benzimidazole-quinolinone compound with potential antineoplastic activity. Dovitinib strongly binds to fibroblast growth factor receptor 3 (FGFR3) and inhibits its phosphorylation, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell death. In addition, this agent may inhibit other members of the RTK superfamily, including the vascular endothelial growth factor receptor; fibroblast growth factor receptor 1; platelet-derived growth factor receptor type 3; FMS-like tyrosine kinase 3; stem cell factor receptor (c-KIT); and colony-stimulating factor receptor 1; this may result in an additional reduction in cellular proliferation and angiogenesis, and the induction of tumor cell apoptosis. The activation of FGFR3 is associated with cell proliferation and survival in certain cancer cell types.

• Doxazosin - A quinazoline with antihypertensive and antineoplastic properties. Doxazosin is an alpha-adrenergic antagonist that selectively inhibits alpha-1 adrenergic receptors. Blockages of the alpha-1 adrenergic action on the vascular smooth muscles lead to a decrease in vascular resistance and antihypertensive activity. This agent also shows high affinity to alpha-1c adrenoceptor, the predominant functional type in the prostate, which may partially attribute to its effect in treatment of benign prostatic hyperplasia. Furthermore, doxazosin induces apoptosis in prostate cancer cells mediated through inhibition of protein kinase B (PKB)/Akt-signaling death receptor regulatory pathway.

• Doxercalciferol - A synthetic analog of vitamin D with potential antineoplastic activity. In the liver, doxercalciferol is converted to its biologically active vitamin D metabolites, which control the intestinal absorption of dietary calcium, the tubular reabsorption of calcium by the kidney and, in conjunction with parathyroid hormone (PTH), the mobilization of calcium from the skeleton. Through interaction with specific receptor proteins in target tissues, these vitamin D metabolites act directly on osteoblasts to stimulate skeletal growth, and on the parathyroid glands to suppress PTH synthesis and secretion. This agent has also been shown to inhibit the growth of retinoblastomas, and may exhibit some antiproliferative activity against prostate cancer cells.

• Doxifluridine - A fluoropyrimidine derivative and oral prodrug of the antineoplastic agent 5-fluorouracil (5-FU) with antitumor activity. Doxifluridine, designed to circumvent the rapid degradation of 5-FU by dihydropyrimidine dehydrogenase in the gut wall, is converted into 5-FU in the presence of pyrimidine nucleoside phosphorylase. 5-FU interferes with DNA synthesis and subsequent cell division by reducing normal thymidine production and interferes with RNA transcription by competing with uridine triphosphate for incorporation into the RNA strand.

• Doxorubicin - An anthracycline antibiotic with antineoplastic activity. Doxorubicin, isolated from the bacterium Streptomyces peucetius var. caesius, is the hydroxylated congener of daunorubicin. Doxorubicin intercalates between base pairs in the DNA helix, thereby preventing DNA replication and ultimately inhibiting protein synthesis. Additionally, doxorubicin inhibits topoisomerase II which results in an increased and stabilized cleavable enzyme-DNA linked complex during DNA replication and subsequently prevents the ligation of the nucleotide strand after double-strand breakage. Doxorubicin also forms oxygen free radicals resulting in cytotoxicity secondary to lipid peroxidation of cell membrane lipids; the formation of oxygen free radicals also contributes to the toxicity of the anthracycline antibiotics, namely the cardiac and cutaneous vascular effects.

• Doxorubicin hydrochloride - The hydrochloride salt of doxorubicin, an anthracycline antibiotic with antineoplastic activity. Doxorubicin, isolated from the bacterium Streptomyces peucetius var. caesius, is the hydroxylated congener of daunorubicin. Doxorubicin intercalates between base pairs in the DNA helix, thereby preventing DNA replication and ultimately inhibiting protein synthesis. Additionally, doxorubicin inhibits topoisomerase II which results in an increased and stabilized cleavable enzyme-DNA linked complex during DNA replication and subsequently prevents the ligation of the nucleotide strand after double-strand breakage. Doxorubicin also forms oxygen free radicals resulting in cytotoxicity secondary to lipid peroxidation of cell membrane lipids; the formation of oxygen free radicals also contributes to the toxicity of the anthracycline antibiotics, namely the cardiac and cutaneous vascular effects.

• Doxorubicin prodrug l-377,202 - A prodrug in which a peptide is covalently conjugated with the anthracycline antineoplastic antibiotic doxorubicin. This complex is hydrolyzed by the enzyme prostate-specific antigen (PSA), resulting in the formation of doxorubicin and leucine-doxorubicin. Selective targeting of these drugs to prostate tumor cells occurs because the hydrolyzing PSA enzyme is localized to the prostate gland. Doxorubicin and leucine-doxorubicin intercalate into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair and RNA and protein synthesis. These agents also produce toxic free-radical intermediates and interact with cell membrane lipids causing lipid peroxidation.

• Doxorubicin prodrug/prodrug-activating biomaterial sq3370 - A formulation consisting of SQL70, a prodrug-activating biomaterial, and SQP33, a prodrug of the anthracycline antineoplastic antibiotic doxorubicin, with potential antineoplastic activity. Upon administration of SQ3370, which consists of the injection of SQL70 at the tumor site followed by the intravenous administration of SQ3370, the prodrug SQP33 binds to, through an as of yet not identifiable mechanism, to SQL70 at the tumor site. After binding, doxorubicin is released over a period of days, intercalates into DNA and interacts with topoisomerase II. This leads to an inhibition of DNA replication and repair, and prevents RNA and protein synthesis. Compared to the systemic administration of doxorubicin alone, SQ3370 may allow for higher and sustained delivery of active doxorubicin directly to the tumor, which may increase its efficacy and limit its off-site, systemic toxicity.

• Doxorubicin-eluting beads - A drug-device combination product consisting of small polymeric beads impregnated with the anthracycline antibiotic doxorubicin with potential antineoplastic activity. The beads consist of polyvinyl alcohol (PVA) microspheres modified with sulfonic acid groups and loaded with doxorubicin. During transarterial chemoembolization (TACE), doxorubicin-eluting beads embolize to the tumor vasculature and release cytotoxic doxorubicin, which may result in both ischemic necrosis of tumor tissue due to mechanical blockage of the tumor vasculature and doxorubicin-mediated inhibition of tumor cell proliferation.

• Doxorubicin-hpma conjugate - A copolymer conjugate of the antineoplastic anthracycline doxorubicin and the water-soluble polymer N-(2-hydroxypropyl) methacrylamide (HPMA). Doxorubicin, an intercalator and a topoisomerase II inhibitor, prevents DNA replication and ultimately inhibits protein synthesis. This agent also generates oxygen free radicals, resulting in cytotoxic lipid peroxidation of cell membrane lipid. HPMA conjugation enhances the permeability and retention of this agent within the tumor vasculature. Poorly cleared by the lymphatic system, this formulation undergoes increased cleavage by tumor cell lysosomal proteinases, resulting in increased, sustained intracellular concentrations of free doxorubicin. Compared to other doxorubicin-containing formulations, this formulation may exhibit an improved toxicity profile due to the lower concentrations of free doxorubicin to which non-malignant tissues are exposed.

• Doxorubicin-loaded egfr-targeting nanocells - A nanocell formulation targeting the epidermal growth factor receptor (EGFR) using bispecific antibodies (bsAb) against EGFR and containing the antineoplastic anthracycline antibiotic doxorubicin, with potential antineoplastic activity. Upon administration of doxorubicin-loaded EGFR-targeting nanocells, the nanocells are stable in the bloodstream and the anti-EGFR bsAb moiety targets and binds to EGFR-expressing tumor cells. Upon binding, the nanocell allows for specific delivery of doxorubicin to tumor cells overexpressing EGFR. Upon endocytosis by the tumor cells, the nanocell is broken down and releases doxorubicin, which intercalates into DNA and interferes with topoisomerase II activity, thereby inhibiting DNA replication and RNA synthesis. Compared to doxorubicin alone or liposomal doxorubicin, targeted delivery of doxorubicin improves efficacy while lowering the toxicity profile. EGFR, a tyrosine kinase receptor, is overexpressed in many cancer cell types. The nanocell is a bacterially derived nanosphere; the bacterial components are unlikely to induce an immune response in the immunosuppressed tumor microenvironment.

• Doxorubicin-magnetic targeted carrier complex - A formulation of the anthracycline antibiotic doxorubicin in which doxorubicin is bound to microscopic beads of activated carbon and iron as a magnetic-targeted carrier (MTC). Doxorubicin, an intercalator and a topoisomerase II inhibitor, prevents DNA replication and ultimately inhibits protein synthesis. This agent also generates oxygen free radicals, resulting in cytotoxic lipid peroxidation of cell membrane lipids. Guided by the placement of a magnet on the body surface overlying a tumor site, the doxorubicin-MTC complex delivers doxorubicin directly to the tumor site, thereby targeting and prolonging the duration of doxorubicin-mediated cytotoxicity to the tumor bed while minimizing systemic toxicity.

• Dpt/bcg/measles/serratia/pneumococcus vaccine - A proprietary lipid emulsion containing five vaccines: diphtheria, pertussis, tetanus (DPT), Bacille Calmette-Guerin (BCG), measles, Serratia marcescens and pneumococcal, with potential immunostimulating activity. Subcutaneous administration of the DPT/BCG/measles/Serratia/pneumococcus vaccine activates the immune system and may both abrogate tumor-induced immune tolerance and induce an antitumor immune response, which may eradicate the tumor.

• Dpt/typhoid/staphylococcus aureus/paratyphoid a/paratyphoid b vaccine - A proprietary lipid emulsion containing five vaccines: diphtheria, pertussis, tetanus (DPT), typhoid, Staphylococcus aureus, paratyphoid A and paratyphoid B, with potential immunostimulating activity. Subcutaneous administration of the DPT/typhoid/Staphylococcus aureus/paratyphoid A/paratyphoid B vaccine activates the immune system and may both abrogate tumor-induced immune tolerance and induce an antitumor immune response, which may eradicate the tumor.

• Dpx-e7 hpv vaccine - A therapeutic vaccine composed of a synthetic peptide consisting of amino acids 11 through 19 of the viral oncoprotein human papillomavirus (HPV) subtype 16 E7 (HPV16-E7 11-19), with potential antineoplastic and immunostimulating activities. Immunization with the DPX-E7 HPV vaccine may stimulate the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the HPV16-E7 protein. HPV type 16 plays a key role in the carcinogenesis of certain cancers.

• Dr5-targeting tetrameric nanobody agonist tas266 - An agonistic tetravalent nanobody, in which the four single, high affinity heavy chain variable domain (VHH) antibodies are separated by a peptide linker, targeting death receptor type 5 (DR5), with potential antineoplastic activity. Upon administration, DR5-targeting tetrameric nanobody agonist TAS266, with its four DR5-specific single-chain antibodies, specifically binds to and activates DR5 receptors. This results in the activation of caspase cascades and induction of apoptosis in DR5-expressing tumor cells. DR5, a cell surface receptor and member of the tumor necrosis factor (TNF)-receptor superfamily, triggers apoptosis. Compared to certain anti-DR5 antibody agonists, TAS266 shows increased receptor activation.

• Dromostanolone propionate - The propionate salt form of dromostanolone, a synthetic anabolic steroid related to dihydrotestosterone that has antiestrogenic effects. Dromostanolone inhibits the growth of estrogen receptor-presenting breast cancers; its virilizing effects limit its clinical usefulness. (NCI)

• Drozitumab -

• Dta-h19 plasmid - A plasmid DNA encoding the A chain of the diphtheria toxin (DT-A) driven by the transcriptional regulatory sequences of human H19, with potential antineoplastic activity. Because the expression of DT-A is under the control of H19 promotor elements, DT-A is selectively expressed in tumor cells capable of turning on H-19. DT-A catalyzes ADP-ribosylation of translation elongation factor 2 (EF-2), resulting in the inhibition of protein synthesis and apoptosis. In addition, DT-A protein released from lysed cells cannot enter and kill neighboring cells because of the absence of the DT-B chain, further enhancing the selective cytotoxicity of this agent. Human H19 is a paternally-imprinted, oncofetal gene encoding an RNA product; it acts as a riboregulator in gene expression and is found at substantial levels in different human tumor cell types while its expression in normal adult tissue is limited.

• Dtrmwxhs-12/everolimus/pomalidomide combination agent dtrm-555 - An orally bioavailable combination of DTRMWXHS-12, a Bruton's tyrosine kinase (BTK) inhibitor, everolimus, a mammalian Target of Rapamycin (mTOR) inhibitor, and pomalidomide, an immunomodulatory drug (IMiD), that may be used for the treatment of B-cell malignancies. Upon oral administration of DTRM-555, the DTRMWXHS-12 component inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways, and leads to an inhibition of the growth of malignant B-cells that overexpress BTK. BTK plays an important role in the development, activation, signaling, proliferation and survival of B-lymphocytes. The everolimus component binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate a complex that binds to and inhibits the activation of mTOR, a key regulatory kinase. Upregulated in some tumors, mTOR is a serine/threonine kinase involved in regulating cellular proliferation, motility, and survival that is located downstream of the PI3K/Akt signaling pathway. The pomalidomide component may inhibit TNF-alpha production, enhance the activity of T cells and natural killer (NK) cells and enhance antibody-dependent cellular cytotoxicity (ADCC). In addition, pomalidomide may inhibit tumor angiogenesis, promote cell cycle arrest in susceptible tumor cell populations, and stimulate erythropoiesis. The combination of a BTK inhibitor, an mTOR inhibitor and an IMiD may work synergistically to kill malignant B-cells and prevent drug resistance.

• Dual igf-1r/insr inhibitor bms-754807 - An oral small molecule inhibitor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (InsR) tyrosine kinases with potential antineoplastic activity. Dual IGF-IR/InsR inhibitor BMS-754807 binds reversibly to and inhibits the activities of IGF-1R and InsR, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. IGF-1R and InsR tyrosine kinases, overexpressed in a variety of human cancers, play significant roles in mitogenesis, angiogenesis, and tumor cell survival.

• Dual-affinity b7-h3/cd3-targeted protein mgd009 - An Fc-bearing humanized bispecific dual-affinity re-targeting (DART) protein composed of Fv regions derived from monoclonal antibodies against the immunoregulatory protein B7-homologue 3 (B7-H3, CD276) and the T-cell surface antigen CD3, with potential immunostimulating and antineoplastic activities. Upon administration of the MGD009 DART protein, the anti-B7-H3 component targets and binds to the cell surface antigen B7-H3; at the same time, the anti-CD3 component binds to human CD3. This cross-links the T-cells to B7-H3-expressing tumor cells, activates and redirects endogenous T-cells to kill B7-H3-expressing tumor cells, and inhibits proliferation of B7-H3-expressing tumor cells. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is overexpressed on certain tumor cell types and on various immune cells but is minimally expressed by normal human tissues. B7-H3 is a negative regulator of T-cell activation and its overexpression plays a key role in immuno-evasion, tumor cell invasion and metastasis, and its expression is correlated with poor prognosis.

• Dubermatinib - An orally available and selective inhibitor of the receptor tyrosine kinase AXL (UFO), with potential antineoplastic activity. Upon administration, dubermatinib targets and binds to AXL and prevents its activity. This blocks AXL-mediated signal transduction pathways and inhibits the epithelial-mesenchymal transition (EMT), which, in turn, inhibits tumor cell proliferation and migration. In addition, TP-0903 enhances chemo-sensitivity to certain other chemotherapeutic agents. AXL, a member of the Tyro3, AXL and Mer (TAM) family of receptor tyrosine kinases and overexpressed by many tumor cell types, plays a key role in tumor cell proliferation, survival, invasion and metastasis; its expression is associated with drug resistance and poor prognosis.

• Duborimycin - An anthracycline antineoplastic antibiotic with therapeutic effects similar to those of doxorubicin. Duborimycin exhibits cytotoxic activity through topoisomerase-mediated interaction with DNA, thereby inhibiting DNA replication and repair and RNA and protein synthesis.

• Dulanermin - A recombinant human soluble protein corresponding to amino acids 114-281 of the Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (RhApo2L/TRAIL) with potential antineoplastic activity. Dulanermin binds to and activates TRAIL receptors 1 and 2 (TRAIL-R1/R2), which may activate caspases and induce p53-independent apoptosis in TRAIL-R1/R2-expressing tumor cells. The pro-apoptotic cell surface receptors TRAIL-R1 and -R2, also known as DR4 (death receptor 4) and DR5 (death receptor 5), are members of the TNF receptor family and are overexpressed by a variety of cancer cell types.

• Duligotuzumab - An immunoglobulin (Ig) G1 monoclonal antibody directed against both human epidermal growth factor receptor 3 (HER3 or ERBB3) and human epidermal growth factor receptor (EGFR), with potential antineoplastic activity. Duligotuzumab binds to both EGFR and HER3 and inhibits their activation. This may prevent EGFR/HER3-mediated signaling and inhibit EGFR/HER3-dependent tumor cell proliferation. In addition, MEHD7945A induces antibody-dependent cell-mediated cytotoxicity (ADCC) against EGR/HER3-expressing tumor cells. EGFR and HER3, members of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, are frequently overexpressed in tumors; their expression is associated with both poor prognosis and drug resistance.

• Dupilumab - A recombinant human monoclonal immunoglobulin G4 (IgG4) antibody directed against the alpha chain of the interleukin-4 receptor (IL-4R alpha) with potential immunomodulatory activities. Upon injection, dupilumab selectively binds to the IL-4R alpha chain. This disrupts IL-4/IL-13 signaling and prevents the activation of downstream pathways that mediate type 2 inflammation and may potentially inhibit tumor cell proliferation, survival, and metastasis. IL-4 and IL-13 receptors are present on the surface of numerous cells involved in the pathophysiology of type-2 helper T-cell (Th2) allergic responses, including B-lymphocytes, eosinophils, dendritic cells (DCs), monocytes, macrophages, basophils, keratinocytes, bronchial epithelial cells, endothelial cells, fibroblasts, and airway smooth muscle cells. Additionally, both IL-4 and IL-13 receptors are overexpressed in a variety of cancers and IL-4 and IL-13 and may serve as biomarkers for cancer aggressiveness. IL-4 and IL-13 are thought to be key regulatory cytokines in the tumor microenvironment (TME) and may play a role in the activation of tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) that mediate tumor cell survival.

• Durvalumab - A monoclonal antibody directed against B7H1 (B7 homolog 1; programmed cell death ligand 1) with potential immunostimulating activity. Upon intravenous administration, durvalumab binds to the cell surface antigen B7H1, thereby blocking B7H1 signaling. This may activate the immune system to exert a cytotoxic T-lymphocyte (CTL) response against B7H1-expressing tumor cells. B7H1, a member of the B7 protein superfamily and a negative regulator of cytokine synthesis, is overexpressed on certain tumor cell types.

• Dusigitumab - A humanized monoclonal antibody directed against insulin-like growth factors 1 and 2 (IGF-1/2) with potential antineoplastic activity. Dusigitumab inhibits IGF1- and IGF2-stimulated activation of membrane-bound IGF receptors and the subsequent triggering of proliferation and survival signaling pathways. This may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. IGF1/2 ligands stimulate cell proliferation, enable oncogenic transformation, and suppress apoptosis; IGF1/2 signaling has been highly implicated in tumorigenesis and metastasis.

• Dutasteride - A synthetic 4-azasteroid compound. Dutasteride competitively and specifically binds to isoenzymes 1 and 2 of 5 alpha-reductase, forming stable enzyme complexes and inhibiting the conversion of testosterone to 5 alpha-dihydrotestosterone (DHT); the reduction in DHT activity may mitigate or prevent enlargement of the prostate gland. The type 2 5 alpha-reductase isoenzyme is primarily active in the reproductive tissues, while the type 1 isoenzyme is also active in skin and the liver.

• Dutpase/dpd inhibitor tas-114 - An orally bioavailable inhibitor of both deoxyuridine triphosphatase (dUTPase) and dihydropyrimidine dehydrogenase (DPD), with potential antineoplastic adjuvant activity. Upon oral administration in combination with a prodrug of the pyrimidine antagonist 5-fluorouracil (5-FU), TAS-114 inhibits (DPD), the liver enzyme responsible for rapid catabolism of 5-FU into inactive metabolites. This prevents first-pass metabolism of 5-FU, allowing oral administration of the 5-FU prodrug and increasing the efficacy of 5-FU. In addition, as a dUTPase inhibitor, TAS-114 enhances the antitumor activity of 5-FU by preventing the hydrolysis and breakdown of 5-fluoro-deoxyuridine triphosphate (FdUTP) and deoxyuridine triphosphate (dUTP), which are active metabolites of 5-FU. This promotes DNA polymerase-dependent incorporation of these antimetabolites into DNA and leads to DNA damage and tumor cell death. Co-administration with TAS-114 allows lower dosing of 5-FU prodrugs, which decreases 5-FU-related toxicity, while maintaining therapeutic levels of 5-FU at the tumor site.

• Duvelisib - An orally bioavailable, highly selective and potent small molecule inhibitor of the delta and gamma isoforms of phosphoinositide-3 kinase (PI3K) with potential immunomodulating and antineoplastic activities. Upon administration, duvelisib prevents the activation of the PI3K delta/gamma-mediated signaling pathways which may lead to a reduction in cellular proliferation in PI3K delta/gamma-expressing tumor cells. Unlike other isoforms of PI3K, the delta and gamma isoforms are overexpressed primarily in hematologic malignancies and inflammatory and autoimmune diseases. By selectively targeting these PI3K isoforms, PI3K signaling in normal, non-neoplastic cells is minimally or not affected which would result in a more favorable side effect profile.

• Duvortuxizumab - An anti-CD19/anti-CD3 bispecific, humanized antibody-like protein, with potential immunostimulatory and antineoplastic activities. Duvortuxizumab possesses two antigen-recognition and binding sites, one for the CD3 complex, a group of T-cell surface glycoproteins that complex with the T-cell receptor (TCR), and one for CD19, a tumor-associated antigen (TAA) overexpressed on the surface of B-cells. Upon administration, duvortuxizumab binds to CD3-expressing T-cells and CD19-expressing cancer cells, thereby crosslinking CD19-expressing tumor B-cells and cytotoxic T-lymphocytes (CTLs). This may result in a potent CTL-mediated cell lysis of CD19-expressing B-lymphocytes. CD19, a B-cell specific membrane antigen, is expressed during normal B-cell development and on B-cell malignancies.

• Dynemicin - An antitumor antibiotic of the enediyne class. It has demonstrated high DNA cleavage activity in the presence of NADPH, antimicrobial and tumor growth-inhibiting properties. Dynemicin recognizes and cleaves conformationally flexible regions of DNA. It attacks bases at 3'-side of purine residues such as 5'-AG, 5'-AT, and 5'-GC sequences. (NCI)

• Dynemicin a - An enediyne antineoplastic antibiotic hybrid containing an anthraquinone moiety isolated from the bacterium Micromonospora chersina. The anthraquinone moiety intercalates into DNA and the benzene diradical intermediate of the enediyne core binds to the minor groove of DNA, resulting in double-strand breaks in DNA, inhibition of DNA replication and apoptosis.

Alphabetic list of antineoplastic agents - 0-9 - A1 - A2 - A3 - A4 - A5 -A6 - B - C - D - E - F - G - H - I - JK - L - M - NO - PQ - R - S - T - UVW - XYZ