Antineoplastic agents uvw

• Uae inhibitor tak-243 - A small molecule inhibitor of ubiquitin-activating enzyme (UAE), with potential antineoplastic activity. UAE inhibitor TAK-243 binds to and inhibits UAE, which prevents both protein ubiquitination and subsequent protein degradation by the proteasome. This results in an excess of proteins in the cells and may lead to endoplasmic reticulum (ER) stress-mediated apoptosis. This inhibits tumor cell proliferation and survival. UAE, also called ubiquitin E1 enzyme (UBA1; E1), is more active in cancer cells than in normal, healthy cells.

• Ubenimex - A microbial metabolite and dipeptide with potential immunomodulatory and antitumor activities. Ubenimex competitively inhibits many aminopeptidases, including B, N and leucine aminopeptidases. Aminopeptidases has been implicated in the process of cell adhesion and invasion of tumor cells. Therefore, inhibiting aminopeptidases may partially attribute to the antitumor effect of ubenimex. This agent also activates T lymphocyte, macrophage and bone marrow stem cell as well as stimulates release of interleukin-1 and -2, thus further enhances its antitumor activity.

• Ubidecarenone nanodispersion bpm31510n - A nanodispersion containing the benzoquinone ubidecarenone (coenzyme Q10), with potential protective, antioxidant and antineoplastic activities. Upon administration, ubidecarenone nanodispersion BPM31510 modulates tumor cell metabolism and causes an anti-Warburg effect by inducing a shift from lactate dependency towards mitochondrial oxidative phosphorylation, and induces tumor cell apoptosis. This inhibits tumor cell proliferation. BPM 31510 also induces the activation and maturation of T-lymphocytes, and changes the surface expression of certain immune checkpoint modulators. In addition, as an antioxidant, ubidecarenone protects against cell damage, by preventing both the peroxidation of lipid membranes and the oxidation of LDL-cholesterol. Ubidecarenone is an essential coenzyme for mitochondrial enzyme complexes involved in oxidative phosphorylation and the production of adenosine triphosphate (ATP).

• Ublituximab - A chimeric recombinant IgG1 monoclonal antibody directed against human CD20 with potential antineoplastic activity. Ublituximab specifically binds to the B cell-specific cell surface antigen CD20, thereby potentially inducing a B cell-directed complement dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) against CD20-expressing B cells, leading to B cell apoptosis. CD20 is a non-glycosylated cell surface phosphoprotein that is exclusively expressed on B cells during most stages of B cell development and is often overexpressed in B-cell malignancies. Ublituximab has a specific glycosylation profile, with a low fucose content, that may enhance its ADCC response against malignant B cells.

• Ulinastatin - A multivalent Kunitz-type serine protease inhibitor derived from human urine, with potential protective, anti-fibrinolytic and anticoagulant activities. Upon administration, ulinastatin (or urinary trypsinogen inhibitor) inhibits the activities of a variety of enzymes, including trypsin, chymotrypsin, thrombin, kallikrein, plasmin, elastase, cathepsin, lipase, hyaluronidase, factors IXa, Xa, XIa, and XlIa, and polymorphonuclear leukocyte elastase. In addition, ulinastatin inhibits the excessive release of proinflammatory mediators, such as tumor necrosis factor-alpha, interleukin-6 and -8, and chemokines. Altogether, this agent may improve the microcirculation, perfusion and function of tissues and may protect organ injury.

• Ulixertinib - An orally available inhibitor of extracellular signal-regulated kinase (ERK) 1 and 2, with potential antineoplastic activity. Upon oral administration, ulixertinib inhibits both ERK 1 and 2, thereby preventing the activation of ERK-mediated signal transduction pathways. This results in the inhibition of ERK-dependent tumor cell proliferation and survival. The mitogen-activated protein kinase (MAPK)/ERK pathway is often upregulated in a variety of tumor cell types and plays a key role in tumor cell proliferation, differentiation and survival.

• Ulocuplumab - An orally bioavailable monoclonal antibody against CXC Chemokine Receptor 4 (CXCR4) with potential antineoplastic activity. Ulocuplumab binds to the chemokine receptor CXCR4, preventing the binding of stromal derived factor-1 (SDF-1) to the CXCR4 receptor and subsequent receptor activation, which may result in decreased tumor cell proliferation and migration. CXCR4, a chemokine receptor belonging to the G protein-coupled receptor family, plays an important role in chemotaxis and angiogenesis and is upregulated in several tumor cell types.

• Umbilical cord blood-derived cd4+/cd25+ t-regulatory cells ck0801 - A preparation composed of allogeneic umbilical cord blood (UCB)-derived, ex vivo expanded and enhanced CD4+/CD25+ T-regulatory cells (Tregs) with potential immunomodulatory activity. Upon administration, the UCB-derived CD4+/CD25+ Tregs CK0801 may promote immunologic homeostasis and prevent autoimmunity by suppressing self-reactive T-cells. This may induce tolerance to allogeneic organ transplants, prevent graft-versus-host disease (GvHD), and suppress autoimmune pathology.

• Umbilical cord blood-derived natural killer cells - A population of allogeneic, cytokine-differentiated, highly lytic natural killer (NK) cells derived from CD34+ cells isolated from human umbilical cord blood (UCB) with potential cytotoxic activity. CD34+ hematopoietic stem cells (HSC) are isolated from human UCB mononuclear cells, differentiated into mature, highly lytic, CD3- CD56+ NK cells, by a specific combination of cytokines that includes stem cell factor (SCF), fms-related tyrosine kinase 3 ligand (Flt3-L), interleukin-15 (IL-15) and insulin-like growth factor-1 (IGF-1), and expanded ex vivo. Upon administration, the UCB-derived NK cells may lyse cancer cells.

• Umbralisib - 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. PI3K-delta inhibitor TGR-1202 inhibits PI3K and prevents the activation of the PI3K/AKT kinase signaling pathway. This decreases proliferation and induces cell death in susceptible tumor cells. Unlike other isoforms of PI3K, PI3K-delta is expressed primarily in tumor cells and cells of the hematopoietic lineage. The targeted inhibition of PI3K-delta allows for PI3K signaling in normal, non-neoplastic cells. PI3K, an enzyme often overexpressed in cancer cells, plays a crucial role in tumor cell regulation and survival.

• Uncaria tomentosa extract - An extract of Uncaria tomentosa (U. tomentosa), also called Cat's claw, a native Amazonian plant belonging to the Rubiaceae species, with potential anti-inflammatory, immunomodulating, antioxidant and antineoplastic activities. Although the exact mechanism(s) by which U. tomentosa extract exerts its effect(s) has yet to be fully elucidated, this extract may inhibit the proliferation of certain types of cancer cells. This extract may modulate inflammatory and immune responses through the stimulation of T- and B-lymphocytes and certain cytokines, including interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-a). Components in U. tomentosa may both induce repair of chemically-induced DNA damage and scavenge free radicals, which may protect against reactive oxygen species (ROS)-mediated cellular damage. In addition, this extract stimulates myelopoiesis, which may prevent chemotherapy-induced neutropenia.

• Upamostat - An orally bioavailable, 3-amidinophenylalanine-derived, second generation serine protease inhibitor prodrug targeting the human urokinase plasminogen activator (uPA) system with potential antineoplastic and antimetastatic activities. After oral administration, upamostat is converted to the active N alpha-(2,4,6-triisopropylphenylsulfonyl)-3-amidino-(L)-phenylalanine-4-ethoxycarbonylpiperazide (WX-UK1), which inhibits several serine proteases, particularly uPA; inhibition of uPA may result in the inhibition of tumor growth and metastasis. uPA is a serine protease involved in degradation of the extracellular matrix and tumor cell migration and proliferation.

• Upifitamab - A proprietary humanized monoclonal antibody against human sodium-dependent phosphate transport protein 2B (SLC34A2; NaPi2b), with potential antineoplastic activity. Upon administration of upifitamab, the antibody targets and binds to NaPi2b expressed on tumor cells. Although the tumor cell killing effects of XMT-1535 are not established, this binding may induce an antibody-dependent cellular cytotoxicity (ADCC)-mediated immune response against NaPi2b-expressing tumor cells, and/or may inhibit NaPi2b-mediated sodium and phosphate ion cotransport activity and ion-dependent tumor cell signaling. NaPi2b, a tumor-associated antigen (TAA), is overexpressed on a variety of tumor cells. It plays a key role in the transport of inorganic phosphate (Pi) and the maintenance of phosphate homeostasis.

• Uproleselan - A synthetic, glycomimetic molecule and E-selectin (CD62E) antagonist, with potential anti-thrombotic, antineoplastic and chemopotentiating activities. Upon administration, uproleselan binds to E-selectin expressed on endothelial cells and prevents their interaction with selectin-E ligand-expressing cancer cells. This may prevent tumor cell activation, migration and metastasis. GMI-1271 also interferes with the binding of selectin E-expressing vascular endothelial cells to selectin-E ligand-expressing monocytes and neutrophils, thereby disrupting their activation. Consequently, this inhibits both the activation of the coagulation cascade and thrombus formation. This agent also prevents both leukocyte activation and inflammation. E-selectin is a cell adhesion molecule involved in cell rolling, signaling and chemotaxis; it also plays a crucial role in inflammatory processes and cancer.

• Uprosertib - An orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Uprosertib binds to and inhibits the activity of Akt, which may result in inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation and the induction of tumor cell apoptosis. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.

• Urabrelimab - A human monoclonal antibody targeting the human cell surface antigen CD47, with potential phagocytosis-inducing and antineoplastic activities. Upon administration, urabrelimab selectively binds to CD47 on tumor cells and blocks the interaction of CD47 with signal regulatory protein alpha (SIRPalpha), an inhibitory protein expressed on macrophages. This prevents CD47/SIRPalpha-mediated signaling and abrogates the CD47/SIRPa-mediated inhibition of phagocytosis. This induces pro-phagocytic signaling mediated by the binding of calreticulin (CRT), which is specifically expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related protein (LRP), expressed on macrophages. This results in macrophage activation and the specific phagocytosis of tumor cells. In addition, blocking CD47 signaling activates both an anti-tumor T-lymphocyte immune response and T cell-mediated killing of CD47-expressing tumor cells. CD47, also called integrin-associated protein (IAP), is a tumor-associated antigen (TAA) expressed on normal, healthy hematopoietic stem cells (HSCs) and overexpressed on the surface of a variety of cancer cells. Expression of CD47, and its interaction with SIRPalpha, leads to the inhibition of macrophage activation and protects cancer cells from phagocytosis, which allows cancer cells to proliferate.

• Uracil ointment - A 0.1% topical formulation of uracil used potentially to lower the incidence of hand-foot syndrome (HFS) (or palmar-plantar erythrodysesthesia) during 5-fluorouracil (5-FU) or 5-FU prodrug capecitabine chemotherapy. Upon local administration of uracil ointment to the skin, uracil competes with capecitabine or 5-FU as substrates for the activating enzyme thymidine phosphorylase and the metabolizing enzyme dihydropyrimidine dehydrogenase. This may prevent the production of 5-FU as well as the breakdown of 5-FU into the toxic metabolites locally. As the 5-FU metabolites are responsible for the presentation of HFS, inhibiting their formation may prevent this adverse effect. By applying a high concentration of uracil locally, the skin toxicities of 5-FU may be countered while preserving the systemic anti-cancer activity of the 5FU.

• Urelumab - A fully human agonistic monoclonal antibody targeting the CD137 receptor with potential immunostimulatory and antineoplastic activities. Anti-CD137 monoclonal antibody specifically binds to and activates CD137-expressing immune cells, stimulating an immune response, in particular a cytotoxic T cell response, against tumor cells. CD137 is a member of the tumor necrosis factor (TNF)/nerve growth factor (NGF) family of receptors and is expressed by activated T- and B-lymphocytes and monocytes; its ligand has been found to play an important role in the regulation of immune responses.

• Uridine phosphorylase inhibitor tk-112690 - A 2,2'-anhydropyrimidine derivative and human uridine phosphorylase (UPase) inhibitor that can be used to suppress mucositis induced by certain chemotherapeutics. Upon administration of UPase inhibitor TK-112690 prior to the administration of certain chemotherapeutic agents, such as methotrexate (MTX), this agent targets, binds to and blocks the activity of UPase, thereby preventing the metabolic breakdown of uridine into uracil. This increases the uridine levels in plasma and may prevent mucositis. By rescuing normal tissue, TK-112690 may enhance the therapeutic index of the chemotherapeutic agent. UPase plays a key role in in pyrimidine metabolism, and catabolizes uridine into uracil and ribose-1-phosphate.

• Urlc10 peptide vaccine - A cancer vaccine containing URLC10 (up-regulated lung cancer 10) epitopes with potential immunostimulatory and antineoplastic activities. Upon administration, URL peptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against URLC10-expressing tumor cells. Up-regulated in lung and esophageal cancers, the function of URLC10 is unknown.

• Urlc10-cdca1-koc1 multipeptide vaccine - A cancer vaccine containing multiple peptide epitopes with potential immunostimulatory and antitumor activities. Peptide epitopes in this vaccine are derived from, URLC10 (up-regulated lung cancer 10), CDCA1 (cell division cycle-associated protein 1), KOC1 (IGF II mRNA Binding Protein 3). Upon administration, URLC10-CDCA1-KOC1 multipeptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells expressing URLC10, CDCA1, KCO1 peptides, resulting in cell lysis and decreased tumor growth.

• Urlc10-ttk-koc1-vegfr1-vegfr2 multipeptide vaccine - A cancer vaccine containing five peptide epitopes with potential immunostimulatory and antitumor activity. Peptide epitopes in this vaccine are derived from: URLC10 (up-regulated lung cancer 10), TTK (TTK protein kinase), KOC1 (IGF II mRNA Binding Protein 3) and VEGFRs (vascular endothelial growth factor receptors) 1 and 2. Upon administration, URLC10-TTK-KOC1-VEGFR1-VEGFR2 multipeptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells expressing URLC10, TTK, KCO1, VEGFR 1 and 2 peptides, resulting in cell lysis and decreased tumor growth.

• Uroacitides - A mixture of peptides, organic acids, pigments, and phenylacetylglutamine isolated from healthy human urine with potential antineoplastic activity. Upon administration, uroacitides, also known as cell differentiation agent II (CDA-II) may inhibit telomerase activity in tumor cells. This may lead to an accumulation of tumor cells in G1 phase and inhibition of tumor cell proliferation.

• Urokinase-derived peptide a6 - An octapeptide (amino acids 136-143) derived from the proteolytic enzyme urokinase plasminogen activator (uPA), with potential antineoplastic activity. A6 is derived from the nonreceptor-binding domain and connecting region of urokinase. Administration of A6 inhibits the interaction of uPA with its receptor uPAR, and may inhibit endothelial cell motility and tumor cell invasion. uPA and uPAR promote extracellular matrix degradation and growth factor activation and correlate positively with angiogenesis, cancer cell invasion and metastasis.

• Ursolic acid - A pentacyclic triterpenoid found in various fruits, vegetables and medicinal herbs, with a variety of potential pharmacologic activities including anti-inflammatory, antioxidative, antiviral, serum lipid-lowering, and antineoplastic activities. Upon administration, ursolic acid may promote apoptosis and inhibit cancer cell proliferation through multiple mechanisms. This may include the regulation of mitochondrial function through various pathways including the ROCK/PTEN and p53 pathways, the suppression of the nuclear factor-kappa B (NF-kB) pathways, and the increase in caspase-3, caspase-8 and caspase-9 activities.

• Usp14/uchl5 inhibitor vlx1570 - An inhibitor of the 19S proteasome-specific deubiquitylating enzymes (DUBs) USP14 and UCHL5, with apoptosis-inducing and antineoplastic activities. Upon administration, VLX1570 specifically binds to both USP14 and UCHL5, thereby blocking their deubiquitylating activity. This blocks the ubiquitin proteasome degradation pathway, prevents the degradation of defective proteins, and leads to an accumulation of poly-ubiquitylated proteins. This induces the unfolded protein response (UPR) and results in both the induction of tumor cell apoptosis and the inhibition of tumor cell growth. USP14 and UCHL5, overexpressed in various tumor cell types, play a key role in the correct folding and deubiquitination of proteins.

• Utomilumab - A human, agonistic immunoglobulin (Ig) G2 monoclonal antibody (mAb) targeting 4-1BB (CD137, TNFRSF9), with potential immunostimulating activity. Upon administration, utomilumab binds to and activates 4-1BB expressed on various immune cells, such as CD8-positive and CD4-positive T cells and natural killer (NK) cells. This enhances 4-1BB-mediated signaling, induces cytokine production and promotes anti-tumor immune responses. 4-1BB, a member of the tumor necrosis factor (TNF)/nerve growth factor (NGF) family of receptors, plays an important role in the regulation of immune responses.

• Uv1 telomerase peptide vaccine - A synthetic, peptide cancer vaccine directed against the human telomerase reverse transcriptase catalytic subunit (hTERT) with potential immunomodulating activity. Vaccination with the UV1 telomerase peptide may stimulate cytotoxic T-cells to recognize and kill telomerase-expressing cells. Telomerase, a reverse transcriptase normally repressed in healthy cells, is overexpressed in most cancer cells and plays a key role in cellular proliferation.

• Uzansertib - An orally available, small molecule and selective ATP-competitive pan-inhibitor of proviral integration sites for Moloney murine leukemia virus (PIM) kinases, with potential antineoplastic activity. Upon oral administration, uzansertib binds to and inhibits the activities of the three PIM isoforms, PIM1, PIM2 and PIM3. This prevents phosphorylation of their downstream targets and inhibits proliferation in cells that overexpress PIMs. PIMs, constitutively active proto-oncogenic serine/threonine kinases upregulated in various types of cancers, play key roles in tumor cell proliferation and survival.

• V930 vaccine - A novel cancer vaccine designed to treat HER-2- and/or CEA-expressing cancers.

• Vaccine-sensitized draining lymph node cells - Cells isolated from lymph nodes from patients, and activated in vitro to generate tumor-specific effector T cells. Lymph nodes in the lymphatics draining tumors often contain T cells that are immunologically sensitized but functionally deficient. Vaccine-sensitized draining lymph node cells are prepared by isolating these lymphocytes in vitro and stimulating them with cytokines to differentiate into mature effector cells. Vaccine-draining lymph node cells may also be produced by pharmacological activation of lymph node-derived lymphocytes with drugs such as ionomycin or with bacterial toxin; these activated lymphocytes may be expanded in culture with cytokines such as interleukin-2 prior to infusion into the patient.

• Vaccinia virus dd-cdsr - A highly tumor-selective vaccinia virus (vv) with an engineered double deletion (DD) of the thymidine kinase (tk) and vaccinia growth factor genes and additions of both a cytosine deaminase (CD) gene and a somatostatin receptor (SR) gene with potential oncolytic viral activity. The tk and vaccinia growth factor gene deletions in intratumorally administered vaccinia virus (vvDD-CDSR) help to restrict its replication and cytolytic activity to tumor cells with large nucleotide pools and tumor cells with activation of the EGFR-Ras pathway. Addition of the CD gene to the viral genome allows control of oncolytic viral infection through the administration of the prodrug 5-fluorocytosine (5-FC), converted by CD to the antimetabolite 5-fluorouracil (5-FU) in cells infected with this agent. Addition of the SR gene allows anatomical localization of vaccinia virus (vvDD-CDSR) through the use of octreotide scintigraphy.

• Vaccinia-gm-csf vaccine - A recombinant vaccinia virus that encodes granulocyte-macrophage colony stimulating factor (GM-CSF). By activating T-cells and macrophages, vaccination with recombinant vaccinia GM-CSF may enhance the host immune system response to poorly immunogenic tumors, resulting in decreased tumor growth.

• Vaccinia-tyrosinase vaccine - A vaccine consisting of recombinant vaccinia virus, based on the modified vaccinia virus Ankara (MVA) that encodes the melanoma-associated antigen tyrosinase. Vaccination with vaccinia-tyrosinase may stimulate the host immune system to mount a cytotoxic T-cell response against tumor cells expressing tyrosinase. Tyrosinase is a melanoma-specific differentiation agent that catalyzes the synthesis of the melanin precursor L-3,4-dihydroxyphenylalanine (L-DOPA).

• Vaccinium myrtillus/macleaya cordata/echinacea angustifolia extract granules - A proprietary suspension formulation prepared from granules of standardized extracts from the fruits of Vaccinium myrtillus, the aerial parts of Macleaya cordata and the roots of Echinacea angustifolia, with potential anti-mucositis, anti-inflammatory, and analgesic activities. The main active ingredients of this formulation include anthocyanosides and procyanidins, benzophenanthridinic alkaloids, and alkylamides from V. myrtillus, M. cordata and E. angustifolia extracts, respectively. Upon administration in the mucosal cavity, the anthocyanosides scavenge free radicals, form a protective barrier on the mucosa, and protect the integrity of the capillary vessels; the benzophenanthridine alkaloids prevent the production of pro-inflammatory cytokines by inhibiting NF-kB and may halt the growth of microorganisms; the alkylamides inhibit cyclooxygenase and 5-lipoxygenase thereby blocking productions of prostaglandin and leukotriene. Furthermore, alkylamides modulate the expression of tumor necrosis factor alpha and other cytokines involved in inflammation processes through cannabinoid type 2 receptors and as cannabinomimetics they may also exert analgesic activity.

• Vactosertib - An orally bioavailable inhibitor of the serine/threonine kinase, transforming growth factor (TGF)-beta receptor type 1 (TGFBR1), also known as activin receptor-like kinase 5 (ALK5), with potential antineoplastic activity. Upon oral administration, vactosertib inhibits the activity of TGFBR1 and prevents TGF-beta/TGFBR1-mediated signaling. This suppresses tumor growth in TGFBR1-overexpressing tumor cells. TGFBR1, which is overexpressed in a variety of tumor cell types, plays a key role in tumor cell proliferation. Expression of TGF-beta promotes tumor cell proliferation, enhances the migration of tumor cells and suppresses the response of the host immune system to tumor cells.

• Vadacabtagene leraleucel - Genetically modified CD3-positive-enriched autologous T-lymphocytes transduced with a replication incompetent gamma retroviral vector expressing a chimeric T-cell antigen receptor (CAR) consisting of an anti-CD19 single chain variable fragment (scFv), fused to the extracellular, transmembrane and intracellular signaling domains of the T-cell co-stimulatory receptor CD28 and the cytoplasmic signaling domain of the zeta chain of the TCR/CD3 complex (CD3-zeta) (CAR19-28z), with potential antineoplastic activities. Upon intravenous administration, vadacabtagene leraleucel,is directed to CD19-expressing tumor cells, and, upon binding to the T-cells, induce selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. The CD28 co-stimulatory molecule signaling domain enhances activation and signaling after recognition of CD19. The inclusion of the CD28 signaling domain may increase proliferation of T-cells and antitumor activity compared to the inclusion of the CD3-zeta chain alone.

• Vadastuximab talirine - An immunoconjugate consisting of a humanized monoclonal antibody that is engineered to contain cysteine residues that are conjugated to the synthetic, DNA cross-linking, pyrrolobenzodiazepine dimer SGD-1882, via the protease-cleavable linker maleimidocaproyl-valine-alanine dipeptide, with potential antineoplastic activity. The monoclonal antibody portion of vadastuximab talirine specifically binds to the cell surface antigen CD33. This causes the internalization of SGN-CD33A, and the release of the cytotoxic moiety SGD-1882. SGD-1882 binds to and crosslinks DNA, which results in both cell cycle arrest and the induction of apoptosis in CD33-expressing tumor cells. CD33, a transmembrane receptor, is expressed on myeloid leukemia cells.

• Vadimezan - A fused tricyclic analogue of flavone acetic acid with potential antineoplastic activity. Vadimezan induces the cytokines tumor necrosis alpha (TNF-alpha), serotonin and nitric oxide, resulting in hemorrhagic necrosis and a decrease in angiogenesis. This agent also stimulates the anti-tumor activity of tumor-associated macrophages.

• Valecobulin - A benzophenone derivative and water soluble valine prodrug of the tubulin binding agent S516, with potential tubulin-inhibiting, vascular-disrupting and antineoplastic activity. Upon administration, valecobulin is converted into its active metabolite S-516 that binds to tubulin and prevents its polymerization in tumor blood vessel endothelial cells and tumor cells. This blocks the formation of the mitotic spindle and leads to cell cycle arrest at the G2/M phase. As a result, this agent disrupts the tumor vasculature and tumor blood flow, deprives tumor cells of nutrients and induces tumor cell apoptosis. In addition, this agent has a direct cytotoxic effect on tumor cells by inhibiting tubulin polymerization.

• Valemetostat - An orally available selective inhibitor of the histone lysine methyltransferases enhancer of zeste homolog 1 (EZH1) and 2 (EZH2), with potential antineoplastic activity. Upon oral administration, valemetostat selectively inhibits the activity of both wild-type and mutated forms of EZH1 and EZH2. Inhibition of EZH1/2 specifically prevents the methylation of lysine 27 on histone H3 (H3K27). This decrease in histone methylation alters gene expression patterns associated with cancer pathways, enhances transcription of certain target genes, and results in decreased proliferation of EZH1/2-expressing cancer cells. EZH1/2, histone lysine methyltransferase (HMT) class enzymes and catalytic subunits of the polycomb repressive complex 2 (PRC2), are overexpressed or mutated in a variety of cancer cells and play key roles in tumor cell proliferation, progression, stem cell self-renewal and migration.

• Valproic acid - A synthetic derivative of propylpentanoic acid with antiepileptic properties and potential antineoplastic and antiangiogenesis activities. In epilepsy, valproic acid appears to act by increasing the concentration of gamma-aminobutyric acid (GABA) in the brain. This agent's antitumor and antiangiogenesis activities may be related to the inhibition of histone deacetylases and nitric oxide synthase, which results in the inhibition of nitric oxide synthesis.

• Valrubicin - A semisynthetic derivative of the antineoplastic anthracycline antibiotic doxorubicin. With a mechanism of action that appears to differ from doxorubicin, valrubicin is converted intracytoplasmically into N-trifluoroacetyladriamycin, which interacts with topoisomerase II, stabilizing the complex between the enzyme and DNA; consequently, DNA replication and repair and RNA and protein synthesis are inhibited and the cell cycle is arrested in the G2 phase. In addition, this agent accumulates in the cell cytoplasm where it inhibits protein kinase C (PKC). Valrubicin is less cardiotoxic than doxorubicin when administered systemically; applied topically, this agent shows excellent tissue penetration. Structurally, the trifluoro-acetyl moiety on the amino group of the glycoside and the valerate moiety appear to result in a lipophilicity that is greater than of doxorubicin, resulting in increased intracytoplasmic concentrations.

• Valspodar - An analogue of cyclosporin-A. Valspodar inhibits p-glycoprotein, the multidrug resistance efflux pump, thereby restoring the retention and activity of some drugs in some drug-resistant tumor cells. This agent also induces caspase-mediated apoptosis.

• Vandetanib - An orally bioavailable 4-anilinoquinazoline. Vandetanib selectively inhibits the tyrosine kinase activity of vascular endothelial growth factor receptor 2 (VEGFR2), thereby blocking VEGF-stimulated endothelial cell proliferation and migration and reducing tumor vessel permeability. This agent also blocks the tyrosine kinase activity of epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that mediates tumor cell proliferation and migration and angiogenesis.

• Vandetanib-eluting radiopaque bead btg-002814 - Radiopaque drug-eluting beads (DEBs) that are loaded with vandetanib, a dual inhibitor of both vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR), with potential antineoplastic, anti-angiogenic and imaging activities. Upon intra-arterial hepatic artery administration of vandetanib (VTB)-eluting Radiopaque beads (VERBs) BTG-002814, the DEBs occlude the tumor blood vessels and deprive tumor cells of oxygen and nutrients, thereby causing hepatic arterial embolization and direct tumor cell death. The VERBs release vandetanib from the beads in a sustained manner. Vandetanib selectively inhibits the tyrosine kinase activity of both VEGFR and EGFR, thereby blocking both VEGF/VEGFR- and EGF/EGFR-stimulated signaling and inhibiting cell proliferation, migration and angiogenesis in VEGFR/EGFR-expressing hepatic tumor cells. The DEBs, controlled release microspherical devices, cause low systemic exposure and prevent systemic toxicity of vandetanib. DEBs also deliver high concentrations of vandetanib in the tumor for a controlled and extended period of time. Use of radiopaque DEBs allows for visualization of both the bead location and the degree of embolization upon imaging.

• Vandortuzumab vedotin - An antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody directed against the six transmembrane epithelial antigen of the prostate 1 (STEAP1), and conjugated, via a protease-cleavable peptide linker, to monomethyl auristatin E (MMAE), an auristatin derivative and a potent microtubule disrupting agent, with potential antineoplastic activity. Upon administration of vandortuzumab vedotin, the monoclonal antibody moiety of vandortuzumab vedotin binds to STEAP1-expressing tumor cells and is internalized, thereby delivering MMAE intracellularly. Proteolytic cleavage releases MMAE, which then binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and tumor cell apoptosis. STEAP1, a tumor-associated antigen (TAA), is overexpressed in a variety of cancer cell types.

• Vantictumab - A monoclonal antibody directed against the Wnt signaling pathway with potential antineoplastic activity. Upon administration, vantictumab binds to certain receptors in the Wnt signaling pathway thereby preventing the activation of the Wnt signaling pathway. This may result in an inhibition of cancer stem cell (CSC) activity and a subsequent inhibition of cancer cell proliferation. The Wnt signaling pathway is dysregulated in many cancer cell types and appears to play a major role in CSC regulation and activity; CSC are tumor initiating cells that are able to self-renew and are responsible for tumor growth and resistance.

• Vanucizumab - A humanized bispecific immunoglobulin G (IgG1) monoclonal antibody targeting both the vascular endothelial growth factor receptor (VEGFR) ligand VEGF-A and the Tie2 receptor ligand angiopoietin-2 (Ang-2), with potential antineoplastic and anti-angiogenic activities. Upon administration of vanucizumab, the anti-VEGF-A arm, which is based on bevacizumab, targets and binds to VEGF-A and the anti-Ang2 arm, which is based on the anti-Ang-2 antibody LC06, targets and binds to Ang2, thereby simultaneously binding and neutralizing both VEGF-A and Ang2. This prevents the activation of both VEGF-A/VEGFR- and Ang2/Tie2-mediated signaling pathways. Altogether, this results in the inhibition of proliferation of VEGF-A- and/or Ang2-overexpressing tumor cells. VEGF-A and Ang2, both upregulated in a variety of tumor cell types, play key roles in tumor cell proliferation, angiogenesis and metastasis.

• Vapreotide - A synthetic cyclic octapeptide analogue of somatostatin with direct and indirect antitumor effects. Vapreotide binds to somatostatin receptors (SSTR), specifically SSTR-2 and to SSTR-5 with a lesser affinity, in the similar behaviors as other octapeptide somatostatin analogues. Like octreotide, this agent has direct and indirect antitumor effects via inhibiting the release of growth hormone and other peptides that regulate release of insulin, gastrointestinal hormones. Furthermore, vapreotide may also be useful for inducing hemostasis in cases of acute hemorrhage of the upper gastrointestinal tract.

• Varlilumab - A human agonistic monoclonal antibody (MoAb) specific for CD27, with potential immunostimulating and antineoplastic activity. Upon administration of varlilumab, this MoAb binds to CD27 and may potentiate the immune response by increasing the cytotoxic T-lymphocyte (CTL) response against CD27-expressing tumor cells. This may lead to growth inhibition of CD27-expressing tumor cells. In addition, this agent may increase the proliferation and activation of antigen-specific T lymphocytes upon co-administration of TAA-containing vaccines, such as dendritic cell vaccines. CD27, a co-stimulatory molecule and member of the tumor necrosis factor family overexpressed in certain tumor cell types, is constitutively expressed on mature T-lymphocytes, memory B cells and natural killer cells and plays an important role in NK cell mediated cytolytic activity and T and B lymphocyte proliferation and activation.

• Varlitinib - An orally bioavailable inhibitor of the epidermal growth factor receptor family with potential antineoplastic activity. Varlitinib selectively and reversibly binds to both EGFR (ErbB-1) and Her-2/neu (ErbB-2) and prevents their phosphorylation and activation, which may result in inhibition of the associated signal transduction pathways, inhibition of cellular proliferation and cell death. EGFR and Her-2 play important roles in cell proliferation and differentiation and are upregulated in various human tumor cell types. Due to the dual inhibition of both EGFR and Her-2, this agent may be therapeutically more effective than agents that inhibit EGFR or Her-2 alone.

• Varlitinib tosylate - The tosylate salt form of varlitinib, an orally bioavailable inhibitor of the epidermal growth factor receptor family with potential antineoplastic activity. Varlitinib selectively and reversibly binds to both EGFR (ErbB-1) and Her-2/neu (ErbB-2) and prevents their phosphorylation and activation, which may result in inhibition of the associated signal transduction pathways, inhibition of cellular proliferation and cell death. EGFR and Her-2 play important roles in cell proliferation and differentiation and are upregulated in various human tumor cell types. Due to the dual inhibition of both EGFR and Her-2, this agent may be therapeutically more effective than agents that inhibit EGFR or Her-2 alone.

• Vascular disrupting agent bnc105 - A vascular disrupting agent (VDA), with potential anti-vascular and antineoplastic activities. Upon administration, vascular disrupting agent BNC105 binds to tubulin and inhibits its polymerization, which results in a blockage of mitotic spindle formation, cell cycle arrest, and disruption of the tumor vasculature. This deprives tumor cells of nutrients and results in tumor cell apoptosis. In addition to its VDA activity, this agent has a direct cytotoxic effect on tumor cells by inhibiting tubulin polymerization.

• Vascular disrupting agent bnc105p - A benzofuran-based vascular disrupting agent (VDA) prodrug with potential anti-vascular and antineoplastic activities. Upon administration vascular disrupting agent BNC105P, the disodium phosphate ester of BNC105, is rapidly converted to BNC105; in activated endothelial cells, BNC105 binds to tubulin and inhibits its polymerization, which may result in a blockage of mitotic spindle formation, cell cycle arrest, and disruption of the tumor vasculature. Hypoxic conditions ensue, depriving tumor cells of nutrients and resulting in tumor cell apoptosis. In addition to its VDA activity, this agent has a direct cytotoxic effect on tumor cells by inhibiting tubulin polymerization. BNC105 is not a substrate for the multidrug-resistance P-glycoprotein (Pgp) transporter.

• Vascular disrupting agent zd6126 - A water-soluble phosphate prodrug of N-acetylcolchinol with potential antiangiogenesis and antineoplastic activities. ZD-6126 is converted in vivo into N-acetylcolchinol. N-acetylcolchinol binds to and destabilizes the tubulin cytoskeleton of endothelial cells in tumor blood vessels, which may result in tumor endothelial cell apoptosis, the selective occlusion of tumor blood vessels, cessation of tumor blood flow, and tumor necrosis.

• Vatalanib - An orally bioavailable anilinophthalazine with potential antineoplastic activity. Vatalanib binds to and inhibits the protein kinase domain of vascular endothelial growth factor receptors 1 and 2; both receptor tyrosine kinases are involved in angiogenesis. This agent also binds to and inhibits related receptor tyrosine kinases, including platelet-derived growth factor (PDGF) receptor, c-Kit, and c-Fms.

• Vatalanib succinate - The succinate salt of vatalanib, an anilinophthalazine derivative, with antineoplastic activity. Vatalanib binds to and inhibits the protein kinase domain of vascular endothelial growth factor receptors 1 and 2; both receptor tyrosine kinases are involved in angiogenesis. This agent also binds to and inhibits related receptor tyrosine kinases, including platelet-derived growth factor (PDGF) receptor, c-Kit, and c-Fms.

• Vecabrutinib - An orally available second-generation, reversible inhibitor of Bruton's tyrosine kinase (BTK; Bruton agammaglobulinemia tyrosine kinase), with potential antineoplastic activity. Upon administration, vecabrutinib non-covalently binds to and inhibits the activity of both wild-type and the C481S mutated form of BTK, a resistance mutation in the BTK active site in which cysteine is substituted for serine at residue 481. This prevents the activation of the B-cell antigen receptor (BCR) signaling pathway and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B-cells that overexpress BTK. Compared to other BTK inhibitors, SNS-062 does not require interaction with the BTK C481 site and inhibits the proliferation of cells harboring the BTK C481S mutation. Other irreversible BTK inhibitors covalently bind to the C481 site to inhibit BTK's activity; the C481S mutation prevents that binding. BTK, a member of the Src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in the development, activation, signaling, proliferation and survival of B-lymphocytes.

• Vector-peptide conjugated paclitaxel - A proprietary conjugate of paclitaxel with antineoplastic activity. Similar to the free drug, the paclitaxel moiety in vector-peptide conjugated paclitaxel binds to and stabilizes tubulin molecules, promoting assembly of microtubules and inhibiting tubulin disassembly which results in the inhibition of cell division. The Kunitz domain-derived vector-peptide carries the conjugated paclitaxel through the blood brain barrier (BBB), bypassing the transmembrane p-glycoprotein (P-gp) efflux pump, which may result in higher concentrations of paclitaxel in the brain parenchyma.

• Vedolizumab - A recombinant humanized immunoglobulin G1 (IgG1) monoclonal antibody directed against the human lymphocyte Peyer's patch adhesion molecule 1 (LPAM-1; alpha4beta7; a4b7), with immunomodulating, anti-inflammatory, and potential antineoplastic activities. Upon administration, vedolizumab selectively binds to integrin a4b7 and prevents the binding of a4b7, expressed on the surface of a subset of T-lymphocytes, to its natural ligand, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is mainly expressed on the surface of gut endothelial cells. This prevents a4b7-mediated signaling, adhesion of lymphocytes to the endothelium and the migration of T-lymphocytes across the endothelium into inflamed gastrointestinal (GI) tissue. By preventing this infiltration to the affected area, inflammation is reduced. The human lymphocyte a4b7 integrin, plays a key role in gastrointestinal (GI) inflammation; it is overexpressed in certain types of cancer cells. The alpha4beta7/MAdCAM-1 signaling pathway plays a critical role in the homing of T-lymphocytes to intestinal tissue.

• Vegf inhibitor ptc299 - An orally bioavailable, small molecule inhibitor of vascular endothelial growth factor (VEGF) synthesis with potential antiangiogenesis and antineoplastic activities. VEGF inhibitor PTC299 targets post-transcriptionally by selectively binding the 5'- and 3'-untranslated regions (UTR) of VEGF messenger RNA (mRNA), thereby preventing translation of VEGF. This inhibits VEGF protein production and decreases its levels in the tumor and bloodstream. In turn, this may result in the inhibition of migration, proliferation and survival of endothelial cells, microvessel formation, the inhibition of tumor cell proliferation, and eventually the induction of tumor cell death. VEGFs are upregulated in a variety of tumor cell types and play key roles during angiogenesis. In addition, PTC299 may enhance the antitumor activity of other chemotherapeutic agents.

• Vegf/hgf-targeting darpin mp0250 - A designed ankyrin repeat proteins (DARPin)-based agent targeting vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), with potential antiangiogenic and antineoplastic activities. Compared to antibodies, DARPins are small in size, have favorable pharmacokinetics and allow for both high affinity binding and efficacy. Upon administration, the VEGF/HGF-targeting DARPin MP0250 binds to and inhibits both HGF and VEGF. This prevents HGF- and VEGF-mediated signaling, and inhibits the growth of HGF/VEGF-overexpressing tumor cells. This agent also prevents osteolysis, due to the inhibitory effect on HGF signaling. HGF and VEGF are overexpressed in a variety of cancer cell types and are associated with increased cell proliferation, migration and adhesion.

• Vegfr inhibitor krn951 - An orally bioavailable quinoline-urea derivative inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1 and 2 with potential antiangiogenesis and antineoplastic activities. VEGFR inhibitor KRN951 inhibits VEGF-induced phosphorylation of VEGFRs 1 and 2, which may result in inhibition of migration, proliferation and survival of endothelial cells, microvessel formation, the inhibition of tumor cell proliferation, and tumor cell death. Expression of VEGFRs may be upregulated in a variety of tumor cell types.

• Vegfr/fgfr inhibitor odm-203 - An orally available inhibitor of the human vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs), with potential antiangiogenic and antineoplastic activities. VEGFR/FGFR inhibitor ODM-203 inhibits both VEGFRs and FGFRs, which may result in the inhibition of VEGFR- and FGFR-mediated signaling. This leads to an inhibition of angiogenesis and cell proliferation in tumor cells overexpressing VEGFR and/or FGFR. Both VEGFRs and FGFRs belong to the superfamily of receptor tyrosine kinases and are upregulated in various tumor cell types.

• Vegfr/pdgfr tyrosine kinase inhibitor tak-593 - An oral formulation containing a small-molecule receptor tyrosine kinase inhibitor of both vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) with potential antineoplastic activity. TAK-593 selectively binds to and inhibits VEGFR and PDGFR, which may result in the inhibition of angiogenesis and tumor cell proliferation.

• Vegfr1-1084 peptide vaccine - A peptide vaccine containing an HLA-A*2402-restricted epitope of vascular endothelial growth factor receptor 1 (VEGFR1 or Flt-1) with potential immunostimulating, antiangiogenic, and antineoplastic activities. Upon vaccination, VEGFR1-1084 peptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against VEGFR1-expressing endothelial cells of the tumor microvasculature, which may inhibit tumor angiogenesis and tumor cell proliferation. VEGFR1, a receptor tyrosine kinase, may be overexpressed on endothelial cells of the tumor microvasculature and is associated with tumor cell proliferation, invasion and tumor angiogenesis. HLA-A*2402 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*2402 may improve antigenicity.

• Vegfr-2 dna vaccine vxm01 - An orally available DNA cancer vaccine containing an attenuated strain of the bacterium Salmonella typhimurium encoding murine vascular endothelial growth factor receptor 2 (VEGFR-2) (VXM01), with potential immunomodulating, anti-angiogenic and antineoplastic activity. Upon oral administration and successful transduction, VEGFR-2 DNA vaccine VXM01 expresses VEGFR-2 in addition to inducing the expression of T-cell activation markers, such as CD25, interleukin-2, the early T-cell activation antigen CD69 and the lymphocyte function-associated antigen LFA-2. The immune response targets the fast growing VEGFR-2 expressing endothelial cells found in the tumor vasculature, thereby blocking angiogenesis which may ultimately inhibit tumor cell proliferation. VEGFR-2 is a receptor tyrosine kinase overexpressed on proliferating endothelial cells in the tumor vasculature.

• Vegfr2 tyrosine kinase inhibitor pf-00337210 - An orally available ATP-competitive inhibitor of the vascular endothelial growth factor receptor type 2 (VEGFR2), with potential anti-angiogenesis and antineoplastic activities. Upon administration, the VEGFR2 tyrosine kinase inhibitor PF-00337210 selectively binds to VEGFR2 and prevents its phosphorylation which may result in an inhibition of migration, proliferation and survival of endothelial cells, microvessel formation, the inhibition of tumor cell proliferation, and may eventually cause tumor cell death. VEGFR2, a receptor tyrosine kinase, is frequently overexpressed by a variety of tumor types.

• Vegfr2/pdgfr/c-kit/flt-3 inhibitor su014813 - An orally-active, tyrosine kinase receptor inhibitor with potential antitumor activity. SU014813 binds to and inhibits the phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor (PDGFR) alpha and beta, c-Kit and Fms-related tyrosine kinase 3 (Flt-3). This leads to an inhibition of cellular proliferation and angiogenesis and an induction of apoptosis.

• Veliparib - A poly(ADP-ribose) polymerase (PARP) -1 and -2 inhibitor with chemosensitizing and antitumor activities. With no antiproliferative effects as a single agent at therapeutic concentrations, ABT-888 inhibits PARPs, thereby inhibiting DNA repair and potentiating the cytotoxicity of DNA-damaging agents. PARP nuclear enzymes are activated by DNA single or double strand breaks, resulting in the poly(ADP-ribosyl)ation of other nuclear DNA binding proteins involved in DNA repair; poly(ADP-ribosyl)ation contributes to efficient DNA repair and to survival of proliferating cells exposed to mild genotoxic stresses as induced by as oxidants, alkylating agents or ionizing radiation.

• Veltuzumab - A humanized monoclonal antibody directed against the CD20 antigen with potential antineoplastic activity. Following binding, veltuzumab triggers complement-dependent cell lysis (CDCL) and antibody-dependent cell-mediated cytotoxicity (ADCC) in cells that overexpress CD20. CD20 antigen is a hydrophobic transmembrane protein located on pre-B and mature B lymphocytes.

• Vemurafenib - An orally bioavailable, ATP-competitive, small-molecule inhibitor of BRAF(V600E) kinase with potential antineoplastic activity. Vemurafenib selectively binds to the ATP-binding site of BRAF(V600E) kinase and inhibits its activity, which may result in an inhibition of an over-activated MAPK signaling pathway downstream in BRAF(V600E) kinase-expressing tumor cells and a reduction in tumor cell proliferation. Approximately 90% of BRAF gene mutations involve a valine-to-glutamic acid mutation at residue 600 (V600E); the oncogene protein product, BRAF(V600E) kinase, exhibits a markedly elevated activity that over-activates the MAPK signaling pathway. The BRAF(V600E) gene mutation has been found to occur in approximately 60% of melanomas, and in about 8% of all solid tumors, including melanoma, colorectal, thyroid and other cancers.

• Venetoclax - An orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. Venetoclax mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells. Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis; its expression is associated with increased drug resistance and tumor cell survival. Compared to the Bcl-2 inhibitor navitoclax, this agent does not inhibit bcl-XL and does not cause bcl-XL-mediated thrombocytopenia.

• Verapamil - A phenylalkylamine calcium channel blocking agent. Verapamil inhibits the transmembrane influx of extracellular calcium ions into myocardial and vascular smooth muscle cells, causing dilatation of the main coronary and systemic arteries and decreasing myocardial contractility. This agent also inhibits the drug efflux pump P-glycoprotein which is overexpressed in some multi-drug resistant tumors and may improve the efficacy of some antineoplastic agents.

• Verpasep caltespen - A recombinant chimeric protein composed of the heat shock protein 65 (Hsp65) from Mycobacterium bovis, and the human papilloma viral (HPV) protein E7. Hsp65, similar to other members of its family of proteins, elicits a strong immune response and may be used to design vaccines against a number of different cancers. E7 protein is involved in carcinogenesis of anal and cervical tumors, and represents a tumor antigen that may be specifically targeted by lymphocytes.

• Verubulin - A quinazoline derivative with potential antineoplastic activities. Verubulin binds to and inhibits tubulin polymerization and interrupts microtubule formation, resulting in disruption of mitotic spindle assembly, cell cycle arrest in the G2/M phase, and cell death. This agent is not a substrate for several subtypes of multidrug resistance ABC transporters, and may be useful for treating multidrug resistant tumors. In addition, as a vascular disrupting agent, verubulin disrupts tumor microvasculature specifically, which may result in acute ischemia and massive tumor cell death. In addition, verubulin is able to cross the blood-brain barrier and accumulate in the brain.

• Verubulin hydrochloride - The hydrochloride salt form of verubulin, a quinazoline derivative with potential dual antineoplastic activities. Verubulin binds to and inhibits tubulin polymerization and interrupts microtubule formation, resulting in disruption of mitotic spindle assembly, cell cycle arrest in the G2/M phase, and cell death. This agent is not a substrate for several subtypes of multidrug resistance ABC transporters, such as P-glycoprotein, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein 1 (BCRP1); therefore, it may be useful for treating multidrug resistant (MDR) tumors that express these transporters. In addition, as a vascular disrupting agent (VDA), verubulin appears to disrupt tumor microvasculature specifically, which may result in acute ischemia and massive tumor cell death.

• Vesencumab - A human IgG1 monoclonal antibody directed against neuropilin-1 (NRP1), with potential antiangiogenic and antineoplastic activities. Upon intravenous administration, vesencumab specifically targets and binds to NRP1; the antibody-NRP1 complex prevents the subsequent coupling of NRP1 to VEGFR2, thereby potentially inhibiting VEGF-mediated signaling and potentially preventing angiogenesis. In combination with other anti-VEGF therapies, vesencumab may enhance their anti-angiogenic effect. NRP1 is a membrane-bound co-receptor normally expressed by endothelial cells and overexpressed by certain tumor cells, and plays a role in angiogenesis, cell survival, migration, and invasion.

• Vesigenurtucel-l - An allogeneic urothelial bladder cancer cell vaccine expressing a recombinant secretory form of the immunoadjuvant heat shock protein gp96 fused with an immunoglobulin Fc domain (gp96-Ig) protein, with potential antineoplastic activity. Upon administration of vesigenurtucel-L, the live, irradiated tumor cells continuously secrete gp96-Ig along with its chaperoned tumor associated antigens (TAAs). This enhances antigen cross presentation to cytotoxic T-lymphocytes (CTLs) and, upon expansion, leads to the induction of a potent CTL response against the TAAs on the endogenous bladder cancer cells. This vaccine also induces a memory T cell response that could fight recurring cancer cells. gp96-Ig is constructed by replacing the KDEL endoplasmic reticulum (ER) retention sequence of gp96 with the Fc portion of the IgG1 protein. This allows for gp96, normally an ER-resident chaperone peptide, to be released from cells.

• Vgef mixed-backbone antisense oligonucleotide gem 220 - A mixed-backbone antisense oligonucleotide that is complementary to a pro-angiogenic vascular endothelial growth factor (VEGF) mRNA sequence. Because of its antiangiogenic properties, GEM 220 has been studied as a potential antineoplastic agent.

• Vgefr/c-kit/pdgfr tyrosine kinase inhibitor xl820 - An orally bioavailable, small molecule receptor tyrosine kinase inhibitor with potential antineoplastic activity. XL820 binds to and inhibits the receptor tyrosine kinases for vascular endothelial growth factor (VEGF), c-kit, and platelet-derived growth factor (PDGF). In tumor models of breast carcinomas, gliomas, and leukemia, this agent exhibits dose-dependent growth inhibition and has been shown to cause tumor regression.

• Viagenpumatucel-l - A proprietary, allogeneic tumor cell vaccine expressing a recombinant secretory form of the heat shock protein gp96 fusion (gp96-Ig) with potential antineoplastic activity. Upon administration of viagenpumatucel-L, the irradiated live tumor cells continuously secrete gp96-Ig along with its chaperoned tumor associated antigens (TAAs) into the blood stream, thereby activating antigen presenting cells, natural killer cells and priming potent cytotoxic T lymphocytes (CTLs) to respond against TAAs on the endogenous tumor cells. Furthermore, this vaccine may induce long-lived memory T cells that could fight recurring cancer cells. gp96-Ig is constructed by replacing the KDEL retention sequence of gp96, normally an endoplasmatic reticulum-resident chaperone peptide, with the Fc portion of mouse and human IgG1.

• Vibecotamab - An anti-CD123/anti-CD3 bispecific monoclonal antibody, in which most of the naturally-occurring Fc domain is maintained, with potential immunostimulatory and antineoplastic activities. Vibecotamab 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 CD123, a tumor-associated antigen (TAA) overexpressed on the surface of certain tumor cells. Upon administration of vibecotamab, this bispecific antibody simultaneously binds to both CD3-expressing T-cells and CD123-expressing cancer cells, thereby crosslinking CD123-expressing tumor cells and cytotoxic T-lymphocytes (CTLs). This may result in potent CTL-mediated cell lysis of CD123-expressing tumor cells. CD123, the interleukin-3 receptor alpha chain, is overexpressed in a variety of hematological malignancies; its expression is low or absent in normal hematopoietic progenitors and stem cells. The Fc domain on the antibody prolongs the half-life of the bispecific antibody and enhances T-cell mediated tumor cell killing through its binding to the Fc receptors.

• Vibostolimab - An antagonistic agent targeting the co-inhibitory molecule and immune checkpoint inhibitor T-cell immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT; T-cell immunoreceptor with Ig and ITIM domains; T-cell immunoglobulin and ITIM domain), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, vibostolimab targets and binds to TIGIT expressed on various immune cells, particularly on tumor-infiltrating T-lymphocytes (TILs) and natural killer (NK) cells, thereby preventing the interaction of TIGIT with its ligands CD112 (nectin-2; poliovirus receptor related-2; PVRL2) and CD155 (poliovirus receptor; PVR; nectin-like protein 5; NECL-5), which are expressed on T-cells, NK cells and certain cancer cells. This enhances the interaction of CD112 and CD155 with the costimulatory receptor CD226 (DNAX Accessory molecule-1; DNAM-1), which is expressed on immune cells, such as NK cells and CD8+ T-cells, and activates CD226-mediated signaling. This activates the immune system to exert a T-cell-mediated immune response against cancer cells. TIGIT, a member of the Ig super family and an immune inhibitory receptor, is overexpressed on tumor antigen-specific CD8+ T-cells and CD8+ TILs and plays a key role in the suppression of T-cell proliferation and activation; it is involved in tumor cell immune evasion, and the inhibition of antiviral immune responses.

• Vilaprisan - An orally available progestin and selective progesterone receptor modulator (SPRM), with potential anti-progesterone and antineoplastic activities. Upon oral administration, vilaprisan competitively binds to the progesterone receptor (PR) in progesterone-responsive tissue and inhibits PR-mediated gene expression. This interferes with progesterone activity in the reproductive system and may inhibit PR-mediated proliferative effects in cells overexpressing PRs. As a result, this agent may suppress ovulation and inhibit proliferation of endometrial tissue or uterine fibroid formation.

• Vinblastine - A natural alkaloid isolated from the plant Vinca rosea Linn. Vinblastine binds to tubulin and inhibits microtubule formation, resulting in disruption of mitotic spindle assembly and arrest of tumor cells in the M phase of the cell cycle. This agent may also interfere with amino acid, cyclic AMP, and glutathione metabolism; calmodulin-dependent Ca++ -transport ATPase activity; cellular respiration; and nucleic acid and lipid biosynthesis.

• Vinblastine sulfate - The sulfate salt of vinblastine, a natural alkaloid isolated from the plant Catharanthus roseus (Madagascar periwinkle) with antineoplastic properties. Vinblastine disrupts microtubule formation and function during mitosis and interferes with glutamic acid metabolism.

• Vincristine - A natural alkaloid isolated from the plant Vinca rosea Linn. Vincristine binds irreversibly to microtubules and spindle proteins in S phase of the cell cycle and interferes with the formation of the mitotic spindle, thereby arresting tumor cells in metaphase. This agent also depolymerizes microtubules and may also interfere with amino acid, cyclic AMP, and glutathione metabolism; calmodulin-dependent Ca++ -transport ATPase activity; cellular respiration; and nucleic acid and lipid biosynthesis.

• Vincristine liposomal - A liposomal formulation of Vincristine designed to reduce toxicity and improve efficacy. Vincristine binds irreversibly to microtubules and spindle proteins in S phase of the cell cycle and interferes with the formation of the mitotic spindle, thereby arresting tumor cells in metaphase. This agent also depolymerizes microtubules and may also interfere with amino acid, cyclic AMP, and glutathione metabolism; calmodulin-dependent Ca++ -transport ATPase activity; cellular respiration; and nucleic acid and lipid biosynthesis. (NCI)

• Vincristine sulfate - The sulfate salt of a natural alkaloid isolated from the plant Catharanthus roseus (Vinca rosea L.) with antimitotic and antineoplastic activities. Vincristine binds irreversibly to microtubules and spindle proteins in S phase of the cell cycle and interferes with the formation of the mitotic spindle, thereby arresting tumor cells in metaphase. This agent also depolymerizes microtubules and may also interfere with amino acid, cyclic AMP, and glutathione metabolism; calmodulin-dependent Ca(2+)-activated ATPase activity; cellular respiration; and nucleic acid and lipid biosynthesis.

• Vincristine sulfate liposome - A sphingomyelin/cholesterol liposomal formulation of vincristine sulfate with potential antineoplastic activity. Vincristine, a vinca alkaloid isolated from the plant Vinca rosea, irreversibly binds to and stabilizes tubulin, thereby interrupting microtubule assembly/disassembly dynamics, thereby preventing the formation of the mitotic spindle and leading to cell cycle arrest in metaphase. Liposomal encapsulation prolongs bioavailability of vincristine, increases its delivery to tumor tissues and reduces its toxicity profile. Compared to standard liposomal delivery, sphingosomal drug delivery further increases circulation time of serum drug and enhances drug accumulation at tumor sites, thereby leading to a further increase in efficacy.

• Vindesine - A synthetic derivative of vinblastine, a naturally occurring vinca alkaloid. Vindesine binds to and stabilizes tubulin, thereby interrupting tubulin polymerization and preventing the formation of the mitotic spindle and cell division; treated cells are unable to undergo mitosis and are arrested in metaphase. This agent also disrupts macromolecular synthesis.

• Vinepidine - A vinca alkaloid compound and semi-synthetic vincristine derivative with antineoplastic activity. Vinepidine binds to and stabilizes tubulin, thereby preventing tubulin polymerization and depolymerization, which result in microtubule assembly and disassembly, respectively. Treated cells are unable to complete mitosis process and are arrested in the metaphase, thereby leading to an inhibition of cell growth.

• Vinflunine - A bi-fluorinated derivative of the semi-synthetic vinca alkaloid vinorelbine with antitubulin, antineoplastic, and antiangiogenic activities. Vinflunine inhibits tubulin assembly without any stablization of assembled microtubules at concentrations comparable to those of other vinca alkaloids such as vincristine, vinblastine and vinorelbine; this effect on microtubule dynamics results in cell cycle arrest in mitosis and apoptosis. Compared to other vinca alkaloids, this agent binds weakly to the vinca-binding site, indicating that vinflunine may exhibit reduced neurotoxicity.

• Vinflunine ditartrate - The ditartrate salt of vinflunine, a bi-fluorinated derivative of the semisynthetic vinca alkaloid vinorelbine with potential antimitotic and antineoplastic activities. Vinflunine binds to tubulin and inhibits tubulin assembly and disrupts microtubule assembly dynamics. This results in cell cycle arrest in mitosis and an induction of apoptosis.

• Vinfosiltine - An aminophosphonate derivative of a vinca alkaloid with potential antineoplastic activity. Vinfosiltine exerts its antineoplastic action just like its parent compound, vinblastine, by immobilizing tubulin molecules, thereby interrupting microtubule assembly/disassembly dynamics. As a result, vinfosiltine prevents mitotic spindle formation and leads to cell cycle arrest in metaphase.

• Vinorelbine - A semisynthetic vinca alkaloid. Vinorelbine binds to tubulin and prevents formation of the mitotic spindle, resulting in the arrest of tumor cell growth in metaphase. This agent may also interfere with amino acid, cyclic AMP. and glutathione metabolism; calmodulin-dependent Ca++ -transport ATPase activity; cellular respiration; and nucleic acid and lipid biosynthesis.

• Vinorelbine tartrate - The ditartrate salt of a semisynthetic vinca alkaloid derived from the leaves of the periwinkle plant (Vinca rosea) with antineoplastic properties. Vinorelbine binds to tubulin, thereby inhibiting tubulin polymerization into microtubules and spindle formation and resulting in apoptosis of susceptible cancer cells. Inhibition of mitotic microtubules correlates with antitumor activity, whereas inhibition of axonal microtubules seems to correlate with vinorelbine's neurotoxicity. Compared to related vinca alkaloids, vinorelbine is more selective against mitotic than axonal microtubules in vitro, which may account for its decreased neurotoxicity. This agent is also a radiation-sensitizing agent.

• Vinorelbine tartrate emulsion - An emulsion containing the tartrate salt of the semisynthetic vinca alkaloid vinorelbine with antineoplastic activity. Vinorelbine binds to tubulin, inhibiting tubulin polymerization into microtubules; cell division is prevented, the cell cycle is arrested metaphase and cell death ensues. In this formulation vinorelbine is emulsified in a homogeneous suspension of nanoparticles, which protects the venous endothelium from coming into direct contact with the active ingredient, potentially reducing vinorelbine-associated venous toxicity at the venous injection site.

• Vinorelbine tartrate oral - An orally bioavailable tartrate salt of vinorelbine, a semisynthetic vinca alkaloid with potential antineoplastic activity. Vinorelbine binds to tubulin, thereby inhibiting tubulin polymerization into microtubules and spindle formation and resulting in apoptosis of susceptible cancer cells. Inhibition of mitotic microtubules correlates with antitumor activity, whereas inhibition of axonal microtubules seems to correlate with vinorelbine's neurotoxicity. Compared to related vinca alkaloids, vinorelbine is more selective against mitotic than axonal microtubules in vitro, which may account for its decreased neurotoxicity. This agent is also a radiation-sensitizing agent.

• Vintafolide - A water-soluble, folate-receptor-targeted conjugate of folate and the vinca alkaloid desacetylvinblastine monohydrazide (DAVLBH) with potential antineoplastic activity. The folate moiety of vintafolide binds to folic acid receptors on the tumor cell surface and the agent is internalized via folate receptor-mediated endocytosis, delivering the tubulin-binding DAVLBH moiety directly into the tumor cell; DAVLBH binding to tubulin results in the disruption of microtubule assembly-disassembly dynamics, cell cycle arrest, and tumor cell apoptosis. Folic acid receptors are frequently upregulated on the surfaces of many tumor cell types. DAVLBH is a derivative of the natural product vinblastine.

• Vinzolidine - An orally active semisynthetic vinca alkaloid with potential antineoplastic activity. Like other vinca alkaloid compounds, vinzolidine binds to and stabilizes tubulin molecules, thereby interfering with microtubule assembly/disassembly dynamics. As a result, vinzolidine prevents mitotic spindle formation and leads to cell cycle arrest in metaphase.

• Vinzolidine sulfate - The sulfate salt of vinzolidine, an orally active semisynthetic vinca alkaloid with potential antineoplastic activity. Like other vinca alkaloid compounds, vinzolidine binds to and stabilizes tubulin molecules, thereby interfering with microtubule assembly/disassembly dynamics. As a result, vinzolidine prevents mitotic spindle formation and leads to cell cycle arrest in metaphase.

• Virulizin - A natural biological response modifier (BRM) isolated from bovine reticuloendothelial tissue. Viruzlin may enhance cell-mediated immune response to tumor cells by direct macrophage activation.

• Vismodegib - An orally bioavailable small molecule with potential antineoplastic activity. Hedgehog antagonist GDC-0449 targets the Hedgehog signaling pathway, blocking the activities of the Hedgehog-ligand cell surface receptors PTCH and/or SMO and suppressing Hedgehog signaling. The Hedgehog signaling pathway plays an important role in tissue growth and repair; aberrant constitutive activation of Hedgehog pathway signaling and uncontrolled cellular proliferation may be associated with mutations in the Hedgehog-ligand cell surface receptors PTCH and SMO.

• Vistusertib - An orally bioavailable inhibitor of the mammalian target of rapamycin (mTOR) with potential antineoplastic activity. Vistusertib inhibits the activity of mTOR, which may result in the induction of tumor cell apoptosis and a decrease in tumor cell proliferation. 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.

• Vitamin d3 analogue ilx23-7553 - A vitamin D3 analogue with potential antineoplastic activity. ILX23-7553 binds to and activates the vitamin D receptor, a cytoplasmic polypeptide expressed in normal vitamin D responsive tissues, but also overexpressed in certain cancers including hepatocellular carcinoma and pancreatic cancer. Mediated through vitamin D receptor, this agent induces cancer cell differentiation, inhibits cancer cell growth and induces apoptosis. In addition, ILX23-7553 may also induce growth arrest and apoptosis independent of vitamin D receptor activation through mechanisms that are not fully elucidated.

• Vitamin e compound - A natural fat-soluble antioxidant with potential chemopreventive activity. Also known as tocopherol, vitamin E ameliorates free-radical damage to biological membranes, protecting polyunsaturated fatty acids (PUFA) within membrane phospholipids and within circulating lipoproteins. Peroxyl radicals react 1000-fold faster with vitamin E than with PUFA. In the case of oxygen free radical-mediated tumorigenesis, vitamin E may be chemopreventive.

• Vitespen - An autologous cancer vaccine derived from tumor-specific gp96 heat shock proteins. Heat shock proteins chaperone peptides through the endoplasmic reticulum, are key regulators of dendritic cell maturation, migration and antigen processing, and are involved in T-cell activation.

• Vlp-encapsulated tlr9 agonist cmp-001 - An agent composed of an unmethylated CpG motif-rich G10 oligonucleotide, which is an agonist of toll-like receptor 9 (TLR9), encapsulated in noninfectious virus-like particles (VLPs), with potential immunostimulating and antineoplastic activities. Upon administration of CMP-001, the VLPs are specifically taken up by and release the oligonucleotide into antigen-presenting cells (APCs), including dendritic cells (DCs). In turn, the oligonucleotide binds to and activates intracellular TLR9. This stimulates immune signaling pathways, induces the innate immune system and may promote the immune system to attack tumor cells. VLPs stimulate the immune system. TLR9, a member of the TLR family, plays a key role in both pathogen recognition and the activation of innate immunity.

• Vocimagene amiretrorepvec - A replication competent retroviral vector, derived from the Moloney murine leukemia virus (MoMLV), encoding a modified form of the yeast suicide gene cytosine deaminase (CD) (Toca 511) used as an antineoplastic adjuvant. Upon transcranial injection, vocimagene amiretrorepvec preferentially enters and transfects tumor cells, and expresses cytosine deaminase, an enzyme that catalyzes the intracellular conversion of the prodrug flucytosine (5-FC) into the antineoplastic agent 5-fluorouracil (5-FU). After administration of 5-FC, the tumor can be eradicated upon activation of 5-FU.

• Vofatamab - A human immunoglobulin G1 (IgG1) monoclonal antibody directed against the fibroblast growth factor receptor type 3 (FGFR3), with potential antineoplastic activity. Upon intravenous administration, vofatamab specifically binds to and inhibits both wild-type and mutated forms of FGFR3. This may result in the inhibition of FGFR3 phosphorylation, and thereby preventing its activation and FGFR3-mediated signal transduction pathways. This results in the inhibition of cell proliferation and the induction of cell death in FGFR3-expressing tumor cells. FGFR3, a receptor tyrosine kinase upregulated or mutated in many tumor cell types, plays a key role in tumor cell proliferation.

• Volasertib - A dihydropteridinone Polo-like kinase 1 (Plk1) inhibitor with potential antineoplastic activity. Volasertib selectively inhibits Plk1, inducing selective G2/M arrest followed by apoptosis in a variety of tumor cells while causing reversible cell arrest at the G1 and G2 stage without apoptosis in normal cells. Plk1, named after the polo gene of Drosophila melanogaster, is a serine/threonine protein kinase involved in regulating mitotic spindle function in a non-ATP competitive manner.

• Volociximab - A chimeric monoclonal antibody with potential antineoplastic activity. Volociximab binds to and inhibits the activity of alpha(5)beta(1) integrin, thereby inhibiting endothelial cell-cell interactions, endothelial cell-matrix interactions, and angiogenesis. (NCI05)

• Von hippel-lindau peptide vaccine - A cancer vaccine composed of peptides derived from a tumor-associated protein encoded by a mutated Von Hippel-Lindau (VHL) oncogene. VHL peptide vaccine may stimulate a cytotoxic T cell response against tumor cells expressing the VHL tumor-associated protein.

• Vonlerolizumab - An agonistic humanized monoclonal antibody against the receptor, OX40 (CD134), with potential immunostimulatory and antineoplastic activities. Upon intravenous administration, vonlerolizumab selectively binds to and activates OX40, by mimicking the action of endogenous OX40 ligand (OX40L). OX40 activation induces proliferation of effector T-lymphocytes and inhibits the activity of regulatory T-cells. In the presence of tumor-associated antigens (TAAs), this may promote an immune response against the TAA-expressing tumor cells. OX40, a cell surface glycoprotein and member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on T-lymphocytes and provides a co-stimulatory signal for the proliferation and survival of activated T-cells.

• Vopratelimab - An agonistic humanized monoclonal antibody that recognizes inducible T-cell co-stimulator (ICOS; CD278), with potential antineoplastic activity. Upon administration, anti-ICOS agonist monoclonal antibody JTX-2011 targets and binds to ICOS expressed on certain T-cells. This stimulates ICOS-mediated signaling, induces proliferation of ICOS-positive T-cells, enhances cytotoxic T-lymphocyte (CTL) survival and augments the CTL-mediated immune response against tumor cells. ICOS, a T-cell specific, CD28-superfamily co-stimulatory molecule and immune checkpoint protein, is normally expressed on certain activated T-cells and plays a key role in the proliferation and activation of T-cells.

• Vorasidenib - An orally available inhibitor of mutated forms of both isocitrate dehydrogenase type 1 (IDH1, IDH1 [NADP+] soluble) in the cytoplasm and type 2 (IDH2, isocitrate dehydrogenase [NADP+], mitochondrial) in the mitochondria, with potential antineoplastic activity. Upon administration, vorasidenib specifically inhibits mutant forms of IDH1 and IDH2, thereby inhibiting the formation of the oncometabolite 2-hydroxyglutarate (2HG) from alpha-ketoglutarate (a-KG). This prevents 2HG-mediated signaling and leads to both an induction of cellular differentiation and an inhibition of cellular proliferation in tumor cells expressing IDH mutations. In addition, vorasidenib is able to penetrate the blood-brain barrier (BBB). IDH1 and 2, metabolic enzymes that catalyze the conversion of isocitrate into a-KG, play key roles in energy production and are mutated in a variety of cancer cell types. In addition, mutant forms of IDH1 and 2 catalyze the formation of 2HG and drive cancer growth by blocking cellular differentiation and inducing cellular proliferation.

• Vorinostat - A synthetic hydroxamic acid derivative with antineoplastic activity. Vorinostat, a second generation polar-planar compound, binds to the catalytic domain of the histone deacetylases (HDACs). This allows the hydroxamic moiety to chelate zinc ion located in the catalytic pockets of HDAC, thereby inhibiting deacetylation and leading to an accumulation of both hyperacetylated histones and transcription factors. Hyperacetylation of histone proteins results in the upregulation of the cyclin-dependant kinase p21, followed by G1 arrest. Hyperacetylation of non-histone proteins such as tumor suppressor p53, alpha tubulin, and heat-shock protein 90 produces additional anti-proliferative effects. This agent also induces apoptosis and sensitizes tumor cells to cell death processes. Vorinostat crosses the blood-brain barrier.

• Vorolanib - An orally available small molecule dual inhibitor targeting human vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs) with antiangiogenic and antineoplastic activities. Vorolanib inhibits all isoforms of VEGFR and PDGFR, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation, and the induction of tumor cell death. Both VEGFRs and PDGFRs are receptor tyrosine kinases that may be upregulated in various tumor cell types. Vorolanib has been shown to reduce tissue toxicity by 95 percent compared with first-generation kinase inhibitors.

• Vorsetzumab mafodotin - An antibody-drug conjugate (ADC) consisting of a humanized monoclonal antibody, directed against the extracellular domain of the human CD70 molecule, conjugated to the auristatin analogue monomethyl auristatin phenylalanine (MMAF), with potential antineoplastic activity. The anti-CD70 antibody moiety of vorsetuzumab mafodotin selectively binds to the extracellular domain of CD70 on tumor cell surfaces. Upon internalization, the MMAF moiety is released, binds to tubulin and inhibits its polymerization, which may result in G2/M phase arrest, tumor cell apoptosis and inhibition of cellular proliferation in tumor cells that overexpress CD70. CD70, the ligand for the costimulatory receptor CD27 and a member of the tumor necrosis factor (TNF) family, is found on the surfaces of various types of cancer cells.

• Voruciclib - A cyclin-dependent kinase (CDK) inhibitor with potential antineoplastic activity. Upon administration, voruciclib selectively inhibits cyclin-dependent kinase 4 (CDK4) and 6 (CDK6). This inhibits retinoblastoma (Rb) protein phosphorylation early in the G1 phase, which prevents CDK-mediated G1-S phase transition and leads to cell cycle arrest. This suppresses DNA replication and decreases tumor cell proliferation. CDK4 and 6 are serine/threonine kinases that are upregulated in many tumor cell types and play a key role in the regulation of cell cycle progression.

• Vosaroxin - A small molecule and a naphthyridine analogue with antineoplastic activity. Vosaroxin intercalates into DNA in a site-specific manner and blocks the re-ligation process carried out by topoisomerase II during DNA replication. As a result, inhibition of DNA replication, RNA and protein synthesis occurs, followed by cell cycle arrest at G2 phase and induced p53-independent apoptosis. This agent shows a favorable toxicity profile in several aspects: it does not generate reactive oxygen species, as do anthracyclines, hence reducing the risk of cardiotoxicity; it is not a P-glycoprotein (P-gp) substrate, and thereby evades the common mechanism for multidrug resistance; and it has limited distribution to normal tissues and a more chemically stable molecular structure.

• Vosilasarm - An orally bioavailable, non-steroidal selective androgen receptor modulator (SARM), with potential tissue-selective androgenic/anti-androgenic activities. Upon oral administration, vosilasarm acts as an agonist in select tissues, such as skeletal muscle and bone, where it binds to and activates androgen receptors (ARs). In the prostate and breasts, RAD140 acts as an antagonist and blocks AR activation and AR-mediated cellular proliferation. Therefore, this agent may improve bone formation and muscle mass and strength, and may inhibit both the growth of the prostate in males and AR-dependent breast cancer cell proliferation. Compared to anabolic agents, SARMs have reduced androgenic properties.

• Voxtalisib - An orally bioavailable small molecule targeting the phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) kinases in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. Voxtalisib inhibits both PI3K kinase and mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in susceptible tumor cell populations. 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 in a PI3K-independent fashion in response to nutrient and energy deprivation. Accordingly, this agent maybe more potent compared to an agent that inhibits either PI3K kinase or mTOR kinase alone.

• Vulinacimab - A fully human monoclonal antibody directed against human vascular endothelial growth factor receptor 2 (VEGFR-2) with potential anti-angiogenesis and antineoplastic activities. Upon administration, vulinacimab specifically binds to and inhibits VEGFR-2, which may inhibit tumor angiogenesis and tumor cell proliferation. VEGFR-2, a tyrosine-protein kinase that plays an essential role in angiogenesis and the proliferation, survival, migration and differentiation of endothelial cells, is overexpressed in certain tumor types.

• Wee1 inhibitor zn-c3 - An inhibitor of the tyrosine kinase Wee1 (Wee1-like protein kinase; Wee1A kinase; WEE1hu) with potential antineoplastic sensitizing activity. Although the exact mechanism of action by which this agent inhibits Wee1 has yet to be disclosed, upon administration of ZN-c3, this agent targets and inhibits Wee1. Inhibition of Wee1 promotes both premature mitosis and a prolonged mitotic arrest leading to cell death in susceptible tumor cells, such as p53-deficient or mutated human cancers that lack the G1 checkpoint, upon treatment with DNA-damaging chemotherapeutic agents. Unlike normal cells, most p53-deficient or mutated human cancers lack the G1 checkpoint as p53 is the key regulator of the G1 checkpoint and these cells rely on the G2 checkpoint for DNA repair to damaged cells. Annulment of the G2 checkpoint may therefore make p53-deficient tumor cells more vulnerable to antineoplastic agents and enhance their cytotoxic effect. Overexpression of Wee1 occurs in several cancer types and high expression of Wee1 is associated with poor outcomes. Wee1 phosphorylates Cdc2 in the Cdc2/cyclin B (CDK1/cyclin B) complex which blocks progression from G2 into mitosis; it negatively regulates the G2 checkpoint by disallowing entry into mitosis in response to DNA damage.

• Wee1 kinase inhibitor debio 0123 - An orally bioavailable inhibitor of the human tyrosine kinase Wee1 (Wee1-like protein kinase; Wee1A kinase; WEE1hu), with potential antineoplastic sensitizing activity. Upon oral administration of Debio 0123, this agent targets, binds to and inhibits Wee1. Inhibition of Wee1 inhibits Cdk1 (Cdc2) phosphorylation, promotes both premature mitosis and a prolonged mitotic arrest, which results in the accumulation of unrepaired DNA damage. This leads to apoptosis in susceptible tumor cells, such as p53-deficient or mutated human cancers that lack the G1 checkpoint, especially in combination with DNA-damaging chemotherapeutic agents. Unlike normal cells, most p53-deficient or mutated human cancers lack the G1 checkpoint as p53 is the key regulator of the G1 checkpoint and these cells rely on the G2 checkpoint for DNA repair to damaged cells. Annulment of the G2 checkpoint may therefore make p53-deficient tumor cells more vulnerable to antineoplastic agents and enhance their cytotoxic effect. Overexpression of Wee1 occurs in several cancer types and high expression of Wee1 is associated with poor outcomes. Wee1 phosphorylates Cdc2 in the Cdc2/cyclin B (CDK1/cyclin B) complex which blocks progression from G2 into mitosis. The Wee1 tyrosine kinase is activated upon DNA damage and regulates the G2-M and S cell cycle checkpoints.

• Whey protein isolate-based nutritional supplement - A nutritional supplement composed of a lactose- and gluten-free whey-based protein isolate and containing various vitamins and minerals, with potential immunomodulating activity. In addition to whey protein isolate, this supplement contains phosphoric acid, L-cysteine, ascorbic acid, vitamin E, zinc, ferrous sulfate, niacinamide, vitamin A, calcium pantothenate, copper, manganese, vitamin D3, pyridoxine, thiamine, riboflavin, folic acid, biotin, iodine, phytonadione, and vitamin B12. Upon administration, whey protein isolate is broken down in the body into cysteine and glutamylcysteine. The available cysteine allows cells to synthesize glutathione (GSH), a tripeptide containing amino acids glycine, glutamate and cysteine, thereby maintaining and increasing intracellular GSH concentrations. GSH plays a major role as an antioxidant, thereby protecting cells from oxidative damage due to harmful substances such as free radicals and reactive oxygen compounds. In addition, the supplement provides necessary vitamins and minerals to the body, which may stimulate the immune system, help with wound healing and regulate metabolic dysregulation.

• White button mushroom extract - A heat-stable extract of white button mushrooms (Agaricus bisporus) with potential chemopreventive and immunomodulating activities. Phytochemicals, such as polysaccharides and especially beta-D-glucans found in the white button mushroom extract, bind to and inhibit the activity of aromatase, an enzyme responsible for the conversion of androgens to estrogens and which is often upregulated in breast cancer cells. The consequent decrease in estrogen production may result in the suppression of estrogen-dependent cellular proliferation. In addition, this extract may promote dendritic cell (DC) maturation, increase interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) production, and may enhance natural killer (NK) cell activity, thus amplifying both innate and T cell-mediated immune responses against cancer cells.

• White carrot - A vegetable, also known as Arracacha, with potential chemoprevenitve, anti-oxidant and protective activities. White carrot contains a variety of nutrients, including minerals and vitamins. Polyacetylenes, including falcarinol, falcarindiol and falcarindiol-3-acetate are mainly responsible for its potential anti-cancer activity.

• Wnt signaling inhibitor sm04755 - An orally bioavailable small molecule inhibitor of the Wnt signaling pathway, with potential antineoplastic activity. Upon oral administration, Wnt signaling inhibitor SM04755 targets and binds to an as of yet undisclosed target in the Wnt signaling pathway, thereby preventing Wnt-mediated signaling. This may inhibit growth of tumor cells in which the Wnt signaling pathway is overactivated. The Wnt signaling pathway is upregulated in many cancers and plays a key role in tumor cell proliferation.

• Wnt signaling pathway inhibitor sm08502 - An orally bioavailable, small molecule inhibitor of the Wnt signaling pathway, with potential antineoplastic activity. Upon oral administration, SM08502 inhibits the expression of genes involved in the Wnt signaling pathway through an as of yet not fully elucidated mechanism. This decreased expression of Wnt pathway-related genes prevents Wnt signaling and may inhibit proliferation of cancer cells in which the Wnt signaling pathway is overactivated. The Wnt signaling pathway is dysregulated in many cancer cell types and plays a crucial role in tumor cell proliferation.

• Wnt-5a mimic hexapeptide foxy-5 - A formylated, six amino acid, Wnt5a-derived peptide and wnt-5a mimetic with potential anti-metastatic activity. Upon intravenous administration, Wnt-5a mimic hexapeptide foxy-5 binds to and activates the wnt-5a receptors, Frizzled-2 and -5, which activates wnt-5a-mediated signaling. Increased wnt-5a signaling may inhibit endothelial tumor cell migration and invasion. This may decrease metastasis of susceptible tumor cells. However, foxy-5 does not affect tumor cell proliferation or apoptosis. Foxy-5 lacks a heparan sulfate-binding domain and contains a formyl group on its NH2-terminal methionine residue which decreases in vivo degradation. Decreased expression of wnt-5a protein is associated with increased motility of certain tumor cell types.

• Wobe-mugos e - An enzymatic preparation containing proteolytic enzymes papain, trypsin and chymotrypsin with potential anti-inflammatory and anticarcinogenic activities. Papain can be extracted from the fruit of the papaya plant. Trypsin and chymotrypsin are serine proteases produced and secreted by the pancreas. Although its exact mechanisms has yet to be fully illustrated, Wobe-Mugos E appears to have the ability to modulate the immune system by degrading cytokines, and cytokine receptors and clearing circulating immune protein complexes, as well as disrupting adhesion molecules. This agent has been shown to reduce chemotherapy-induced toxicity, inhibit tumor cell proliferation and prolong survival rates.

• Wt1 124-138 peptide vaccine - A synthetic peptide vaccine consisting of a HLA-DR15-restricted human Wilms' Tumor protein-1 (WT1) peptide comprised of amino acids 124 through 138, a HLA class II-restricted WT1 peptide, with potential immunomodulating and antitumor activities. Vaccination with WT1 124-138 peptide may stimulate a CD4-positive helper T-lymphocyte-mediated immune response against WT1 expressing cells. Activated helper T-cells stimulate dendritic cells, and activate the proliferation of other T-lymphoctes and B-lymphocytes. This causes tumor cell lysis and inhibition of cancer cell proliferation in WT1-overexpressing tumor cells. WT1, a zinc finger DNA-binding protein, is overexpressed in most types of leukemia and in a variety of solid cancers.

• Wt1 126-134 peptide vaccine - A synthetic peptide vaccine consisting of the amino acids 126 through 134 of the human Wilms' Tumor protein-1 (WT1) with potential antitumor activity. WT1, a tumor associated antigen, is overexpressed in most types of leukemia and in a variety of solid cancers. Vaccination with WT1 126-134 peptide vaccine may induce a WT1-specific cytotoxic T-lymphocyte (CTL) response against WT1 expressing cells, resulting in cell lysis and inhibition of cancer cell proliferation.

• Wt1 235-243 peptide vaccine - A synthetic peptide vaccine consisting of a HLA-A24-restricted human Wilms' Tumor protein-1 (WT1) peptide comprised of amino acids 235 through 243, a MHC class I-restricted peptide, with potential immunomodulating and antitumor activities. Vaccination with WT1 235-243 peptide may induce a WT1-specific cytotoxic T-lymphocyte (CTL) response against WT1 expressing cells, resulting in cell lysis and inhibition of cancer cell proliferation. WT1, a zinc finger DNA-binding protein, is overexpressed in most types of leukemia and in a variety of solid cancers.

• Wt1 247-261 peptide vaccine - A synthetic peptide vaccine consisting of a HLA-DRw53-restricted human Wilms' Tumor protein-1 (WT1) peptide comprised of amino acids 247 through 261, a HLA class II-restricted WT1 peptide, with potential immunomodulating and antitumor activities. Vaccination with WT1 247-261 peptide may stimulate a CD4-positive helper T-lymphocyte-mediated immune response against WT1 expressing cells. Activated helper T-cells stimulate dendritic cells, and activate the proliferation of other T-lymphoctes and B-lymphocytes. This causes tumor cell lysis and inhibition of cancer cell proliferation in WT1-overexpressing tumor cells. WT1, a zinc finger DNA-binding protein, is overexpressed in most types of leukemia and in a variety of solid cancers.

• Wt1 analog peptide vaccine - A peptide vaccine comprised of an epitope of human Wilms tumor 1 (WT-1) with potential antineoplastic activity. WT-1, a transcription factor, is overexpressed in most types of leukemia and in some solid cancers. Vaccination with the WT-1 analog peptide vaccine may induce a cytotoxic T-lymphocyte (CTL) response against WT-1 expressing cells, resulting in cell lysis and inhibition of cancer cell proliferation.

• Wt1 mrna-electroporated autologous dendritic cell vaccine - A cancer vaccine containing autologous dendritic cells electroporated with full-length mRNA encoding Wilms' tumor 1 (WT1) antigen with potential immunostimulatory and antineoplastic activities. Upon administration, WT1 mRNA-electroporated autologous dendritic cell vaccine may elicit a cytotoxic T-cell (CTL) response against tumor cells expressing WT1. Wt1 is frequently overexpressed in a variety of tumor cell types and often correlates with disease progression and poor prognosis.

• Wt1 peptide vaccine ocv-501 - A peptide cancer vaccine comprised of a peptide derived from Wilms tumor gene 1 (WT1) protein, with potential immunomodulating and antineoplastic activities. Upon subcutaneous administration, WT1 peptide vaccine OCV-501 may stimulate a CD4-positive helper T-lymphocyte-mediated immune response against WT1 expressing cells. WT1 protein, a zinc finger DNA-binding protein, is overexpressed in leukemic cells and in some solid tumors.

• Wt1 peptide vaccine wt2725 - A peptide cancer vaccine comprised of a peptide derived from Wilms tumor gene 1 (WT1) protein, with potential immunomodulating and antineoplastic activities. Upon administration, WT2725 may induce a specific cytotoxic T-lymphocyte (CTL) response against WT1-overexpressing tumor cells. WT1 protein, a zinc finger DNA-binding protein, is overexpressed in leukemic cells and in a vast number of non-hematological solid tumors.

• Wt1 peptide-loaded allogeneic dendritic cell vaccine - A cell-based cancer vaccine composed of donor-derived dendritic cells (DCs) loaded with three, human leukocyte antigen A2 (HLA-A2)-binding peptides derived from the human tumor-associated antigen (TAA) Wilms tumor protein 1 (WT1), with potential immunomodulating and antineoplastic activities. Upon vaccination, WT1 peptide-loaded allogeneic DC vaccine exposes the immune system to WT1-derived peptides and may stimulate the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against WT1-expressing cancer cells, which could result in tumor cell lysis. WT1, a transcription factor, is overexpressed in leukemic cells and in various solid tumors, and only minimally in normal tissues; its expression often correlates with disease progression and poor prognosis. HLA-A2 is an MHC class I molecule that presents antigenic peptides to CD8+ T-cells; restricting the peptides to those epitopes that bind most efficiently to HLA-A2 may improve antigenic peptide immunogenicity.

• Wt1 protein-derived peptide vaccine dsp-7888 - A peptide cancer vaccine comprised of peptides derived from the Wilms tumor gene 1 (WT1) protein, with potential immunomodulating and antineoplastic activities. Upon administration, WT1 protein-derived peptide vaccine DSP-7888 may induce a specific cytotoxic T-lymphocyte (CTL) response against WT1-overexpressing tumor cells. In addition, DSP-7888 induces a helper T-lymphocyte-mediated immune response against WT1 expressing tumor cells. WT1 protein, a zinc finger DNA-binding protein and transcription factor, is overexpressed in leukemic cells and in many non-hematological solid tumors.

• Wt1/prame/survivin-specific cytotoxic t-lymphocytes - A preparation of cytotoxic T-lymphocytes (CTLs) specifically reactive to the tumor-associated antigens (TAAs) human Wilms tumor protein (WT1), preferentially expressed antigen of melanoma (PRAME; melanoma antigen preferentially expressed in tumors; Opa-interacting protein 4; OIP-4), and survivin (baculoviral IAP repeat-containing protein 5; BIRC5), with potential immunomodulating and antineoplastic activities. Upon collection of peripheral blood mononuclear cells (PBMCs), these cells are stimulated with antigen presenting cells (APCs) pulsed with WT1, PRAME and survivin peptides; reactive T-cells are selectively expanded. Upon administration of the WT1/PRAME/Survivin-specific CTLs, these T-cells induce a CTL-mediated response against tumor cells expressing WT1, PRAME, or survivin, leading to tumor cell lysis and inhibition of tumor cell proliferation. WT1, PRAME, and survivin, are expressed on certain tumor cell types and play key roles in tumor cell proliferation and survival.

• Wt1/psma/htert-encoding plasmid dna ino-5401 - A preparation composed of three separate DNA plasmids encoding the tumor-associated antigens (TAAs) Wilms tumor gene-1 (WT1), prostate-specific membrane antigen (PSMA) and human telomerase reverse transcriptase (hTERT), with potential immunostimulating and antineoplastic activites. Upon intramuscular delivery and electroporation of the WT1/PSMA/hTERT-encoding plasmid DNA INO-5401, the genes are translated into their respective proteins inside the cell. The expressed proteins activate the immune system and induce a cytotoxic T-lymphocyte (CTL)-mediated response against cells expressing the WT1, PSMA and hTERT antigens, causing tumor cell lysis. hTERT, WT1 and PSMA are upregulated in many cancer cell types.

• Wt1-a10/as01b immunotherapeutic gsk2130579a - An immunotherapeutic consisting of the recombinant fusion protein WT1-A10 combined with the adjuvant ASO1B with potential immunostimulating and antineoplastic activities. Upon administration, WT1-A10/AS01B immunotherapeutic GSK2130579AWT1 may induce a WT1-specific cytotoxic T-lymphocyte (CTL) response against WT1-expressing tumor cells, resulting in cell lysis and the inhibition of cellular proliferation. The tumor-associated antigen WT1 (Wilms tumor protein-1) is overexpressed in most types of leukemia and in a variety of solid cancers. WT1-A10 is a 292 amino acid recombinant fusion protein consisting of a 12-mer truncated tat sequence (leader sequence) and amino acids number 2-281 of the WT1 sequence; ASO1B consists of a combination of the adjuvants monophosporyl lipd A (MPL) and Q21.

• Wt1-h/k-help-survivin-h/k-help-mage-a4-h / k-help-muc1-22 peptide-loaded autologous dendritic cells - A preparation of autologous dendritic cells (DCs) pulsed with helper/killer-hybrid epitope long peptides (H/K-HELP) of Wilms tumor 1 (WT1 H/K-HELP), survivin, melanoma-associated antigen 4 (MAGE-4) and human mucin 1-22 (Muc1-22), with potential immunomodulating and antineoplastic activities. Upon administration of WT1-H/K-HELP-survivin-H/K-HELP-MAGE-A4-H / K-HELP-Muc1-22 peptide-loaded autologous DCs may stimulate the host immune system to mount an anti-tumoral cytotoxic T lymphocyte (CTL), T-helper (Th), and antibody responses against WT1-, survivin-, MAGE-4- and Muc1-22-expressing cancer cells, resulting in tumor cell lysis. WT1, survivin, MAGE-4 and Muc-1-22, tumor-associated antigens (TAAs), are overexpressed on a variety of cancer cells. The DCs loaded with the long fusion polypeptides, comprising of one or more helper epitopes and killer epitopes, may enhance antigen-specific CTL and Th cell production more efficiently than when the DCs are loaded with a mixture of helper epitope and killer epitope.

• Wt1-loaded artificial adjuvant vector cell immunotherapeutic asp7517 - A preparation of artificial adjuvant vector cells (aAVCs) composed of cells from the cell line HEK293, which is derived from human embryonic kidney cells, that are transfected with the natural killer T (NKT) immune cell receptor cluster of differentiation 1d (CD1d) and loaded with the glycolipid and CD1d ligand alpha-galactosylceramide (alpha-GalCer) on the cell surface, and loaded with the full-length tumor-associated antigen (TAA) Wilms' tumor 1 (WT1), with potential immunomodulating and antineoplastic activities. Upon administration of the WT1-loaded aAVC immunotherapeutic ASP7517, the alphaGalCer on the cell surface activates invariant NKT (iNKT) cells, thereby eliciting WT1-specific NKT cell responses against ASP7517. This in turn activates a natural killer (NK) cell response against WT1-expressing tumor cells. Also, the WT1 released from destroyed ASP7517 is taken up by antigen-presenting cells (APCs), mainly by dendritic cells (DCs), which in turn activates cytotoxic T-lymphocytes (CTL) and results in a CTL-mediated immune response against WT1-expressing tumor cells, thereby further destroying WT1-expressing tumor cells. In addition, the activation of antigen-specific memory T cells provides long-lasting anti-tumor effects against the WT1-expressing tumor cells.

• Wt1-sensitized allogeneic t-lymphocytes - A population of allogeneic T-cells sensitized with Wilms tumor 1 (WT1) antigen with potential immunostimulatory and antineoplastic activities. Upon administration, WT1-sensitized T cells may bind to and lyse WT1-expressing tumor cells. WT1 antigen, a zinc finger DNA-binding protein acting as a transcriptional activator or repressor depending on the cellular or chromosomal context, is overexpressed in leukemic cells and in a vast number of nonhematological solid tumors.

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