Antineoplastic agents m

• N-(5-tert-butyl-3-isoxazolyl)-n-(4-(4-pyridinyl)oxyphenyl) urea - An orally available isoxazole urea with potential anti-tumor activity. In preclinical trials, N-(5-tert-butyl-3-isoxazolyl)-N-(4-(4-pyridinyl)oxyphenyl)urea inhibited raf kinase, an enzyme capable of reversing the phenotype of ras-transformed cells and blocking tumor growth. (NCI)

• N,n-dibenzyl daunomycin - The N-alkylated analogue of the anthracycline antineoplastic antibiotic daunomycin. N,N-Dibenzyl Daunomycin interacts with topoisomerase II, thereby inhibiting DNA replication and repair and promoting DNA fragmentation. This agent is less cardiotoxic than daunomycin.

• Na17.A2 Peptide vaccine - A peptide cancer vaccine comprised of human leukocyte antigen HLA-A2-restricted peptide derived from a metastatic melanoma cell line of patient NA17, with potential immunomodulating and antineoplastic activity. NA17.A2 peptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against tumors that express this antigen, which may result in a reduction in tumor size. This NA17 specific antigen, encoded by an intron sequence of N-acetylglucosaminyltransferase V (GnT-V) gene, is expressed in about 50% of melanomas.

• Na-17/mage-3.A2/ny-eso-1 peptide vaccine - A peptide cancer vaccine consisting of peptides derived from the melanoma antigen NA-17, the human leukocyte antigen HLA-A2-restricted human melanoma antigen 3 (MAGE-3.A2) and the cancer-testis antigen (NY-ESO-1), with potential immunostimulating and antineoplastic activities. Upon administration, the NA-17/MAGE-3.A2/NY-ESO-1 peptide vaccine may stimulate the immune system to mount a cytotoxic T-cell (CTL) response against tumor cells expressing NA-17, MAGE-3.A2 and NY-ESO-1, resulting in tumor cell lysis. The tumor-associated antigens (TAAs) NA-17, MAGE-3.A2 and NY-ESO-1 are overexpressed in a variety of cancer cell types.

• Na17-a antigen - A specific melanoma antigen protein derived from a patient (NA17) with cutaneous melanoma metastases. When administered in a vaccine formulation, NA17-A antigen may stimulate a cytotoxic T lymphocyte (CTL) response against tumors that express this antigen, which may result in a reduction in tumor size. The NA17-A antigen is part of the enzyme N-acetyl glucosaminyltransferase V (GnT-V). Approximately half of melanomas have been found to express significant levels of this atypical protein, which is not expressed by normal tissues.

• Nab-paclitaxel - A Cremophor EL-free, albumin-stabilized nanoparticle formulation of the natural taxane paclitaxel with antineoplastic activity. Paclitaxel binds to and stabilizes microtubules, preventing their depolymerization and so inhibiting cellular motility, mitosis, and replication. This formulation solubilizes paclitaxel without the use of the solvent Cremophor, thereby permitting the administration of larger doses of paclitaxel while avoiding the toxic effects associated with Cremophor.

• Nab-paclitaxel/rituximab-coated nanoparticle ar160 - A formulation composed of nanoparticle albumin-bound (nab) paclitaxel, which is an albumin-stabilized nanoparticle containing the natural taxane paclitaxel, non-covalently coated with rituximab, a recombinant chimeric murine/human antibody directed against the CD20 antigen found on B-lymphocytes, with potential antineoplastic activity. Upon administration of nab-paclitaxel/rituximab nanoparticle AR160, the rituximab moiety specifically binds to CD20 and targets this formulation to CD20-positive tumor cells. Paclitaxel binds to and stabilizes microtubules, which prevents depolymerization and inhibits cellular motility, mitosis, and replication. This leads to cell death of the CD20-expressing tumor cells that were targeted by this agent. The combination of albumin-stabilization and rituximab-targeting allows for higher efficacy and decreased paclitaxel-induced toxicity as it specifically targets CD20-expressing tumor cells. Rituximab may also induce complement-dependent cytotoxicity and antibody-dependent cellular toxicity.

• Nadofaragene firadenovec - A replication-deficient recombinant adenovirus encoding human interferon alpha-2b with potential antineoplastic activity. Upon intravesical administration, nadofaragene firadenovec infects nearby tumor cells and expresses INF alpha-2b intracellularly which activates the transcription and translation of genes whose products mediate antiviral, antiproliferative, antitumor, and immune-modulating effects.

• Nadofaragene firadenovec/syn3 - A non-replicating recombinant adenovirus type 5 (Ad5)-vector encoding the gene for interferon alpha-2b (IFN alpha-2b) and the gene transfer enhancement agent Syn 3, with potential antineoplastic activity. Upon intravesical administration, nadofaragene firadenovec/Syn3 transfects both cancerous and normal bladder cells, and the adenovirus secretes interferon (IFN alpha-2b) into the bladder. IFN exerts a direct antitumor killing effect and a bystander effect, thereby killing adjacent, non-transfected cancerous bladder cells. Syn 3 enhances the ability of the adenoviral vector to transfect cells.

• Nagrestipen - A recombinant form of a human macrophage inflammatory protein-1 alpha (MIP1-alpha) with a substitution of aspartate to alanine at position 26, with potential immunomodulating and radiotherapy potentiating activity. Intravenous administration of nagrestipen after local tumor irradiation enhances the anti-tumor effect of ionizing radiation at the irradiated site as well as the antitumor effect at non-irradiated tumor sites (known as the abscopal effect). The abscopal effect appears to be attributed to this agent's ability to recruit and activate leukocytes, such as monocytes, dendritic cells, natural killer cells and T lymphocytes, thereby initiating an anti-tumor immune response against cancer cells. MIP1-alpha, also known as chemokine (C-C motif) ligand 3, is a ligand for the chemokine receptors CCR1, CCR4 and CCR5 that are involved in immune and inflammatory responses.

• Namirotene - A synthetic analogue of retinoic acid with differentiation inducing and potential antineoplastic activities. Like other retinoic acid agents, namirotene binds to and activates retinoic acid receptors (RARs), thereby altering the expression of certain genes leading to cell differentiation and decreased cell proliferation in susceptible cells.

• Namodenoson - An orally bioavailable, synthetic, highly selective adenosine A3 receptor (A3AR) agonist with potential antineoplastic activity. Namodenoson selectively binds to and activates the cell surface-expressed A3AR, deregulating Wnt and NF-kB signal transduction pathways downstream, which may result in apoptosis of A3AR-expressing tumor cells. A3AR, a G protein-coupled receptor, is highly expressed on the cell surfaces of various solid tumor cell types, including hepatocellular carcinoma (HCC) cells, and plays an important role in cellular proliferation.

• Nampt inhibitor ot-82 - An orally bioavailable, small molecule inhibitor of the nicotinamide adenine dinucleotide (NAD)-synthesizing enzyme nicotinamide phosphoribosyltransferase (NAMPT; NAMPRTase), with potential antineoplastic activity. Upon oral administration, NAMPT inhibitor OT-82 binds to and inhibits the activity of NAMPT. This depletes cellular NAD and inhibits NAD-dependent enzymes, both of which are needed for rapid cell proliferation; this results in cell death in NAMPT-overexpressing cancer cells. NAMPT, an enzyme that is responsible for maintaining the intracellular NAD pool, plays a key role in the regulation of cellular metabolism and has cytokine-like activities. NAMPT is overexpressed in a variety of cancers and metabolic disorders; tumor cells rely on NAMPT activity for their NAD supply.

• Nanafrocin - A quinone antibiotic isolated from Streptomyces rosa var. notoensis with activity against gram-positive bacteria, mycoplasmas and fungi. Within an organism, nanaomycin A is first reduced by flavin or NADH dehydrogenase then rapidly autooxidized leading to the production of singlet molecular oxygen (O2-). The increase in intracellular O2- results in inhibition of DNA, RNA and cell-wall peptidoglycan synthesis. Further, nanaomycin A may have antineoplastic properties resulting from a reduction in DNA methylation by inhibiting DNA methyltransferase 3B (DNMT3B) and reactivating the tumor suppressor gene RASSF1A.

• Nanatinostat - An orally bioavailable, second-generation hydroxamic acid-based inhibitor of histone deacetylase (HDAC), with potential antineoplastic activity. Nanatinostat targets and inhibits HDAC, resulting in an accumulation of highly acetylated histones, the induction of chromatin remodeling, and the selective transcription of tumor suppressor genes; these events result in the inhibition of tumor cell division and the induction of tumor cell apoptosis. This agent may upregulate HSP70 and downregulate anti-apoptotic Bcl-2 proteins more substantially than some first-generation HDAC inhibitors. HDACs, upregulated in many tumor cell types, are a family of metalloenzymes responsible for the deacetylation of chromatin histone proteins.

• Nanocell-encapsulated mir-16-based microrna mimic - A nanoparticle-based formulation composed of a microRNA 16 (miR-16) mimic, a double-stranded, 23 base pair, synthetic RNA molecule, encapsulated in nonliving bacterial minicells and coated with anti-epidermal growth factor receptor (EGFR) antibodies, with potential antineoplastic activity. Upon intravenous administration and subsequent transfection, nanocell-encapsulated miR-16-based microRNA mimic targets EGFR-expressing tumor cells and facilitates the restoration of expression of the miR-16 family. This leads to the downregulation of the expression of tumor promoting genes and the inhibition of tumor cell growth. In addition, restoration of miR-16 expression sensitizes the tumor cell to certain chemotherapeutic agents. miR-16, a family of microRNAs, is critical to the regulation of gene expression and appears to have a tumor suppressor function; its expression is downregulated in various cancer cell types.

• Nanoparticle albumin-bound docetaxel - A nanoparticle albumin-bound formulation of the taxane docetaxel with antineoplastic activity. Docetaxel is a semi-synthetic, second-generation taxane derived from a compound found in the European yew tree Taxus baccata. Docetaxel binds to and stabilizes tubulin, thereby inhibiting microtubule disassembly which results in cell-cycle arrest at the G2/M phase and cell death. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and displays immunomodulatory and pro-inflammatory properties by inducing various mediators of the inflammatory response. This nanoparticle albumin-bound formulation solubilizes docetaxel without the use of the nonionic solubilizer Cremophor ELP, permitting the administration of larger doses of docetaxel while avoiding Cremophor ELP-associated toxicity.

• Nanoparticle albumin-bound rapamycin - The macrolide antibiotic rapamycin bound to nanoparticle albumin with immunosuppressant (see sirolimus) and potential antiangiogenic and antineoplastic activities. Rapamycin binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate a complex that binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase. In turn, inhibition of mTOR may result in the inhibition of the phosphatidylinositol 3 (PI-3) kinase/Akt pathway and vascular endothelial cell growth factor (VEGF) secretion, which may result in decreased tumor cell proliferation and tumor angiogenesis. The binding of water-insoluble rapamycin to nanoparticle albumin permits the albumin-mediated endocytosis of rapamycin by tumor cells and endothelial cells.

• Nanoparticle albumin-bound thiocolchicine dimer nab-5404 - A nanoparticle albumin-bound formulation of a thiocolchicine dimer, an inhibitor of both microtubule and topoisomerase I (TOP1), with antineoplastic and vascular disrupting activities. Upon administration of nanoparticle albumin-bound thiocolchicine dimer nab-5404, this agent binds to tubulin and inhibits its polymerization, which blocks mitotic spindle formation and leads to cell cycle arrest and tumor endothelial cell apoptosis. This disrupts the tumor vasculature and leads to tumor necrosis. In addition, nab-5404 binds to topoisomerase I (TOPI) and inhibits its activity. This results in the inhibition of the repair of single-strand DNA breaks, DNA replication, and tumor cell growth in susceptible tumor cell populations. The nanoparticle albumin-based formulation permits the albumin-mediated endocytosis of the thiocolchicine dimer by tumor cells and endothelial cells.

• Nanoparticle paclitaxel ointment sor007 - A topical ointment composed of the water-insoluble taxane paclitaxel that has been processed to form uncoated nanoparticles, with potential antineoplastic activity. Upon topical administration of nanoparticle paclitaxel ointment SOR007 to the affected area, and following epithelial and dermal penetration, paclitaxel binds to tubulin and inhibits the disassembly of microtubules, which leads to the inhibition of cell division, thereby halting the proliferation of rapidly-dividing tumor cells. The nanoparticles in the nanoparticle paclitaxel ointment are produced through a specific proprietary submicron particle production.

• Nanoparticle-based paclitaxel suspension - A nanoparticle-based suspension containing the water-insoluble taxane paclitaxel, with potential antineoplastic activity. Upon intraperitoneal administration, paclitaxel binds to tubulin and inhibits the disassembly of microtubules, which leads to the inhibition of cell division. The nanoparticle-based formulation is devoid of toxic solvents, such as cremophor; therefore, this agent has fewer side effects than the standard, solvent-based paclitaxel formulation.

• Nanoparticle-encapsulated doxorubicin hydrochloride - A formulation of nanoparticles encapsulating the hydrochloride salt form of the anthracycline antibiotic doxorubicin, with potential antitumor activity. Upon intravenous administration, doxorubicin intercalates DNA, interferes with the activity of topoisomerase II, and causes DNA adducts and other DNA damage, resulting in tumor cell growth inhibition and apoptosis. This agent also interacts with cell membrane lipids causing lipid peroxidation. Delivery of doxorubicin in nanoparticles may improve drug penetration into tumors and may circumvent the tumor cells multidrug resistance mechanisms and may therefore be effective in chemoresistant tumor cells.

• Nanoscale coordination polymer nanoparticles cpi-100 - A preparation of self-assembled core-shell nanoscale coordination polymer (NCP) nanoparticles containing an as of yet undisclosed payload with potential immunostimulating and antineoplastic activities. Upon intravenous administration, NCP nanoparticle formulation CPI-100 delivers its payload to tumor cells, which may lead to enhanced immune-mediated killing and regression of tumor cells.

• Nanosomal docetaxel lipid suspension - A lipid-based nanosomal formulation of the poorly soluble, semi-synthetic, second-generation taxane docetaxel, with potential antineoplastic activity. Upon intravenous injection, docetaxel binds to and stabilizes tubulin, which inhibits microtubule disassembly and results in both cell cycle arrest at the G2/M phase and cell death. This liposomal formulation solubilizes docetaxel without the use of toxic solvents, such as polysorbate 80. This permits the administration of larger doses of docetaxel and improves the drug's safety profile by avoiding solvent-associated toxicities, such as hypersensitivity reactions and neurotoxicity. In addition, the nanosomal lipid-based delivery of docetaxel improves drug penetration into tumors and decreases drug clearance, all of which prolong the duration of docetaxel's therapeutic effects.

• Napabucasin - An orally available cancer cell stemness inhibitor with potential antineoplastic activity. Even though the exact target has yet to be fully elucidated, napabucasin appears to target and inhibit multiple pathways involved in cancer cell stemness. This may ultimately inhibit cancer stemness cell (CSC) growth as well as heterogeneous cancer cell growth. CSCs, self-replicating cells that are able to differentiate into heterogeneous cancer cells, appear to be responsible for the malignant growth, recurrence and resistance to conventional chemotherapies.

• Naphthalimide analogue unbs5162 - An amonafide (naphthalimide) derivative and pan-antagonist of chemokine ligand (CXCL) expression, with potential anti-angiogenic activity. Although UNBS5162 is a derivative of amonafide, this agent appears to have a different profile to that of amonafide and its exact mechanism of action remains to be fully elucidated. This agent seems to decrease the expression of various proangiogenic CXCL chemokines in vitro and may have synergistic effects with radiotherapy or chemotherapy. CXCLs are small cytokines in the CXC chemokine family that are overexpressed in certain cancers; CXCL-mediated signaling plays a key role in angiogenesis and tumor progression.

• Naptumomab estafenatox - A recombinant fusion protein consisting of the antigen-binding fragment of a monoclonal antibody directed towards the tumor-associated oncofetal trophoblast glycoprotein antigen 5T4 attached to a mutated form of superantigen staphylococcal enterotoxin E (SEA/E-120), with immunomodulating and antineoplastic activities. The Fab moiety of naptumomab estafenatox binds to 5T4, an antigen expressed by various tumor cells. In turn, the superantigen binds to both major histocompatibility complex class II molecules and to the T-cell receptor beta chain, which results in a massive activation of T lymphocytes and induces a potent T-cell-mediated killing of tumor cells.

• Naquotinib - An orally available, irreversible, third-generation, mutant-selective, epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon oral administration, ASP8273 covalently binds to and inhibits the activity of mutant forms of EGFR, including the T790M EGFR mutant, thereby preventing EGFR-mediated signaling. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. ASP8273 preferentially inhibits mutated forms of EGFR including T790M, a secondarily acquired resistance mutation, and may have therapeutic benefits in tumors with T790M-mediated resistance when compared to other EGFR tyrosine kinase inhibitors. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced as compared to non-selective EGFR inhibitors which also inhibit wild-type EGFR.

• Naratuximab emtansine - An immunoconjugate that consists of a humanized IgG1 antibody K7153A against the cell-surface antigen CD37 and covalently linked via the uncleavable, maleimide-derived thioether-based linker SMCC to the maytansinoid DM1, with potential pro-apoptotic and cytotoxic activities. Upon administration of naratuximab emtansine, the antibody moiety of IMGN529 binds to CD37 on tumor B-cells and induces an antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), thereby showing pro-apoptotic activity. In addition, after the internalization of this agent and lysosomal degradation, the DM1 moiety binds to tubulin and inhibits tubulin polymerization and microtubule assembly, resulting in a disruption of microtubule activity and cell division, and eventually causing cell death in CD37-positive B-cells. CD37, a transmembrane glycoprotein, is overexpressed in B-cell malignancies. Compared to reducible, cleavable linkers, the non-reducible SMCC linker shows increased stability in plasma.

• Narnatumab - A fully human monoclonal antibody against RON (recepteur d'origine nantais; macrophage stimulating 1 receptor), with potential antineoplastic activity. Anti-RON monoclonal antibody IMC-RON8 binds to RON, thereby preventing binding of its ligand hepatocyte growth factor-like protein (HGFL or macrophage-stimulating protein (MSP)). This may prevent RON receptor-mediated signaling and may prevent cellular proliferation in tumor cells overexpressing RON. RON, a receptor tyrosine kinase, is overexpressed in a variety of epithelial cancer cell types and plays an important role in cellular proliferation, migration and invasion.

• Natalizumab - A humanized recombinant IgG4 monoclonal antibody directed against the alpha4 subunit of the integrins alpha4beta1and alpha4beta7 with immunomodulating, anti-inflammatory, and potential antineoplastic activities. Natalizumab binds to the alpha4-subunit of alpha4beta1 and alpha4beta7 integrins expressed on the surface of all leukocytes except neutrophils, inhibiting the alpha4-mediated adhesion of leukocytes to counter-receptor(s) such as vascular cell adhesion molecule-1 (VCAM-1); natalizumab-mediated disruption of VCAM-1 binding by these integrins may prevent the transmigration of leukocytes across the endothelium into inflamed parenchymal tissue. Integrins are cellular adhesion molecules (CAMs) that are upregulated in various types of cancer and some autoimmune diseases; alpha4beta1 integrin (VLA4) has been implicated in the survival of myeloma cells, possibly by mediating their adhesion to stromal cells.

• Natural ifn-alpha opc-18 - A proprietary preparation of natural human interferon alpha (IFN alpha) with potential immunomodulatory and antineoplastic activities. Natural human interferon alpha OPC-18 binds to cell-surface IFN alpha receptors (IFNARs), resulting in the transcription and translation of genes whose products mediate antiviral, antiproliferative, and immune-modulating effects. IFN alpha is a type I interferon produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products and is the primary interferon produced by virus-induced leukocyte cultures. In addition to its pronounced antiviral activity, it activates NK cells.

• Natural killer cells zrx101 - A population of activated, immortalized, interleukin-2 (IL-2)-dependent, cytotoxic natural killer (NK) cells with potential antitumor activity. Natural killer cells ZRx101 are derived from NK-92 cells, having been modified to target tumor-associated antigens (TAAs) upregulated in certain types of cancer. The NK-92 cell line was originally isolated from a patient with large granular lymphocytic (LGL) leukemia/lymphoma.

• Navarixin - An orally available small molecule antagonist of the C-X-C motif chemokine receptor 1 (CXCR1; interleukin-8 receptor alpha; IL8RA) and 2 (CXCR2; interleukin-8 receptor beta; IL8RB), with potential immunomodulating and antineoplastic activities. Upon administration, navarixin binds to and inhibits the activation of CXCR 1 and 2. This inhibits CXCR1/2-mediated signaling, reduces both recruitment and migration of immunosuppressive myeloid-derived suppressor cells (MDSCs) and neutrophils in the tumor microenvironment (TME), inhibits inflammatory processes and abrogates the immunosuppressive nature of the TME. This allows effector cells, such as natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs), to kill and eliminate cancer cells. This inhibits tumor cell migration, metastasis, angiogenesis and tumor cell proliferation. CXCR 1 and 2, G protein-coupled receptor proteins located on myeloid cells and certain tumor cells, play key roles in the immunosuppressive nature of the TME, tumor metastasis, therapy-resistance, myeloid cell suppression, and inflammation.

• Navicixizumab - A bispecific monoclonal antibody directed against both the Notch ligand delta-like 4 (DLL4) and the human tyrosine kinase vascular endothelial growth factor (VEGF), with potential anti-angiogenic and antineoplastic activities. The anti-DLL4 moiety of navicixizumab specifically binds to DLL4, prevents its interaction with Notch receptors, and inhibits Notch-mediated signaling and gene transcription, which may both block tumor angiogenesis and inhibit tumor cell growth. The anti-VEGF moiety binds to VEGF and prevents the binding of VEGF to its receptor, which blocks VEGF-mediated signaling and further inhibits the growth and maintenance of tumor blood vessels. The expression of DLL4 is highly restricted to the vascular endothelium; DLL4/Notch signaling is required for the development of functional tumor blood vessels. The expression of the pro-angiogenic growth factor VEGF is associated with tumor angiogenesis and tumor cell proliferation and invasion.

• Navitoclax - An orally active, synthetic small molecule and an antagonist of a subset of the B-cell leukemia 2 (Bcl-2) family of proteins with potential antineoplastic activity. Navitoclax selectively binds to apoptosis suppressor proteins Bcl-2, Bcl-XL, and Bcl-w, which are frequently overexpressed in a wide variety of cancers, including those of the lymph, breast, lung, prostate, and colon, and are linked to tumor drug resistance. Inhibition of these apoptosis suppressors prevents their binding to the apoptotic effectors Bax and Bak proteins, thereby triggering apoptotic processes in cells overexpressing Bcl-2, Bcl-XL, and Bcl-w. This eventually reduces tumor cell proliferation.

• Navoximod - An orally available inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), with potential immunomodulating and antineoplastic activities. Upon administration, navoximod targets and binds to IDO1, a cytosolic enzyme responsible for the oxidation of the essential amino acid tryptophan into kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, this agent increases tryptophan levels, restores the proliferation and activation of various immune cells, including dendritic cells (DCs), natural killer (NK) cells, and T-lymphocytes, and causes a reduction in tumor-associated regulatory T-cells (Tregs). Activation of the immune system, which is suppressed in many cancers, may induce a cytotoxic T-lymphocyte (CTL) response against the IDO1-expressing tumor cells. IDO1 is overexpressed by a variety of tumor cell types and plays an important role in immunosuppression. Tryptophan depletion is associated with immunosuppression caused by T-cell suppression.

• Navy bean powder - The powder form of the cooked navy bean with potential antioxidant and chemopreventive activities. Navy beans are rich in fiber, minerals, vitamins, and phytochemicals such as flavonoids and phytosterols. They appear to prevent carcinogenesis by inducing tumor cell apoptosis. Intake of navy bean powder may have a beneficial effect on intestinal microflora.

• Nazartinib - An orally available, irreversible, third-generation, mutant-selective epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon oral administration, nazartinib covalently binds to and inhibits the activity of mutant forms of EGFR, including the T790M EGFR mutant, thereby preventing EGFR-mediated signaling. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. EGF816 preferentially inhibits mutated forms of EGFR including T790M, a secondarily acquired resistance mutation, and may have therapeutic benefits in tumors with T790M-mediated resistance when compared to other EGFR tyrosine kinase inhibitors. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced as compared to non-selective EGFR inhibitors which also inhibit wild-type EGFR.

• Ncmtrna oligonucleotide andes-1537 - A proprietary antisense oligonucleotide targeting a novel non-coding mitochondrial RNA (ncmtRNA), with potential antineoplastic activity. Upon administration, Andes-1537 binds to ncmtRNA, which is overexpressed in rapidly proliferating cells, such as cancer cells, and not expressed in resting cells. This may decrease the expression of the ncmtRNA, which may inhibit cell proliferation and eventually induce apoptosis in susceptible cancer cells. The proprietary mitochondrial RNA (mtRNA) belongs to the family of non-coding RNAs (ncRNA); it contains an inverted repeat (IR) of 815 nucleotides (nt), which can form a covalent link to the 5' end of the mitochondrial 16S ribosomal RNA (16S mtrRNA).

• N-dihydrogalactochitosan - A carbohyrate polymer in which galactose molecules are attached to the amino groups of the glucosamine polymer chitosan, with potential imunostimulating activity. After a tumor ablation and upon intratumoral injection directly into the location of the ablated tumor, N-dihydrogalactochitosan may trigger a tumor-specific systemic immune response when exposed to tumor-associated neoantigens that are liberated by tumor ablation. This may kill tumor cells.

• Necitumumab - A fully human IgG1 monoclonal antibody directed against the epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Necitumumab binds to and blocks the ligand binding site of EGFR, thereby preventing the activation and subsequent dimerization of the receptor. This may lead to an inhibition of EGFR-dependent downstream pathways and so inhibition of EGFR-dependent tumor cell proliferation and metastasis. EGFR, a member of the epidermal growth factor family of extracellular protein ligands, may be overexpressed on the cell surfaces of various tumor cell types.

• Nedaplatin - A second-generation cisplatin analogue with antineoplastic activity. Containing a novel ring structure in which glycolate is bound to the platinum by a bidentate ligand, nedaplatin forms reactive platinum complexes that bind to nucelophillic groups in DNA, resulting in intrastrand and interstrand DNA cross-links, apoptosis and cell death. This agent appears to be less nephrotoxic and neurotoxic compared to both cisplatin and carboplatin.

• Nedd8 activating enzyme e1 inhibitor tas4464 - An inhibitor of NEDD8 (neural precursor cell expressed, developmentally down-regulated 8) activating enzyme E1 (NAE), with potential antineoplastic activity. Upon administration, TAS4464 selectively binds to and inhibits NAE, which prevents NAE/NEDD8-mediated signaling and prevents the NEDD8 conjugation of cullin-RING ligase complexes (CRLs). This inactivates the CRLs leading to an accumulation of CRL substrate proteins, such as CDT1, p27, p21 and phosphorylated IkappaB, and inactivates nuclear factor-kappaB (NF-kB) as well as downregulates anti-apoptotic proteins. This causes cell cycle dysregulation, induces apoptosis, and inhibits tumor cell proliferation and survival. NAE catalyzes the first step in the NEDD8 conjugation (neddylation) pathway which controls cancer cell growth and survival through activation of CRLs.

• Nelarabine - An arabinonucleoside antimetabolite with antineoplastic activity. Nelarabine is demethoxylated by adenosine deaminase to become biologically active 9-beta-D-arabinosylguanine (ara-G); ara-G incorporates into DNA, thereby inhibiting DNA synthesis and inducing an S phase-dependent apoptosis of tumor cells.

• Nelipepimut-s - A cancer vaccine comprised of a human leukocyte antigen (HLA) A2/A3 restricted HER2/neu (human epidermal growth factor receptor 2; ErbB2) nonapeptide derived from the extracellular domain of the HER2 protein, with potential immunomodulating and antineoplastic activities. Upon intradermal injection, nelipepimut-S may induce a specific cytotoxic T-lymphocyte (CTL) response against HER2/neu-expressing tumor cells. HER2/neu, a tumor-associated antigen and a member of the epidermal growth factor receptor family of tyrosine kinases, is overexpressed in various tumor cell types and plays a key role in tumorigenesis.

• Nelipepimut-s plus gm-csf vaccine - A cancer peptide vaccine comprised of a human leukocyte antigen (HLA) A2/A3 restricted HER2/neu (ERBB2) peptide from the extracellular domain of the HER2 protein (E75 peptide) and combined with the immunoadjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF), with potential immunomodulating and antineoplastic activity. Upon intradermal injection, nelipepimut-S plus GM-CSF vaccine may induce a specific cytotoxic T-lymphocyte (CTL) response against HER2/neu-expressing tumor cell types. HER2/neu, a tumor-associated antigen and a member of the epidermal growth factor receptor family of tyrosine kinases, is overexpressed in various tumor cell types. GM-CSF potentiates the antitumor immune response.

• Nemorubicin - A morpholinyl analogue of the anthracycline doxorubicin with antineoplastic activity. Nemorubicin is metabolized via the P450 CYP3A enzyme to a highly cytotoxic derivative. Unlike most anthracyclines, nemorubicin is a topoisomerase I inhibitor and appears to exert its effect through the nucleotide excision repair (NER) system. In addition, this agent does not show cross-resistance with other anthracyclines.

• Nemorubicin hydrochloride - The hydrochloride salt form of nemorubicin, a morpholinyl analogue of the anthracycline doxorubicin with antineoplastic activity. Nemorubicin is metabolized via the P450 CYP3A enzyme to a highly cytotoxic derivative. Unlike most anthracyclines, nemorubicin is a topoisomerase I inhibitor and appears to exert its effect through the nucleotide excision repair (NER) system. In addition, this agent does not show cross-resistance with other anthracyclines.

• Neoantigen dna-based pancreatic cancer vaccine - A personalized, polyepitope DNA vaccine composed of a DNA plasmid encoding multiple, highly immunogenic tumor associated antigens (TAAs) that are specifically expressed by a patient's pancreatic cancer cells, including personalized epitopes of the TAA mesothelin, with potential immunostimulatory and antineoplastic activities. Upon intramuscular administration and electroporation of the neoantigen DNA-based pancreatic cancer vaccine, the expressed TAAs induce a specific cytotoxic T-lymphocyte (CTL) immune response against tumor cells expressing the neoantigens.

• Neoantigen peptide vaccine - A peptide-based cancer vaccine consisting of patient-specific antigens, which are immunogenic and unique to the patient's tumor, with potential immunomodulating and antineoplastic activities. Upon vaccination with the neoantigen peptide vaccine, the peptides stimulate the host immune system to mount a specific cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the neoantigens, which results in tumor cell lysis.

• Neoantigen vaccine gen-009 - A peptide-based, personalized cancer vaccine consisting of patient-specific mutated synthetic long peptides (SLPs), which are immunogenic and unique to the patient's tumor, with potential immunomodulating and antineoplastic activities. Upon subcutaneous vaccination with the personalized neoantigen peptide vaccine GEN-009, and administration along with the immunoadjuvant poly-ICLC, the peptides stimulate the host immune system to mount a specific and potent cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the neoantigens, which results in tumor cell lysis. The Antigen Lead Acquisition System (ATLAS) will be used to identify neoantigens in each patient's tumor that are recognized by their CD4 and/or CD8 T-cells and will be incorporated into GEN-009 in the form of SLPs. Each personalized vaccine contains between four and twenty SLPs.

• Neoantigen-based glioblastoma vaccine - A peptide-based, personalized glioblastoma cancer vaccine consisting of patient-specific glioblastoma derived immunogenic mutated epitopes (neoantigens), with potential immunomodulating and antineoplastic activities. Vaccination with the neoantigen-based glioblastoma vaccine stimulates the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells expressing the neoantigens, which results in tumor cell lysis. Neoantigens are tumor-specific antigens derived from mutated proteins that are present only in a specific tumor.

• Neoantigen-based melanoma-poly-iclc vaccine - A peptide-based melanoma cancer vaccine consisting of neoantigens and peptides derived from patient-specific melanoma immunogenic epitopes, combined with the immunostimulant poly-ICLC with potential immunomodulating and antineoplastic activities. Vaccination with the neoantigen-based melanoma vaccine stimulates the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells expressing the neoantigens, which results in tumor cell lysis. The adjuvant poly-ICLC, composed of double-stranded RNA molecules of polyinosinic-polycytidylic acid stabilized with poly L-lysine in carboxymethylcellulose, is a ligand for toll-like receptor-3 (TLR3) and induces the release of cytokines which may help to boost the immune response against the selected neoantigens.

• Neoantigen-based renal cell carcinoma-poly-iclc vaccine - A peptide-based renal cell carcinoma (RCC) vaccine consisting of neoantigens and peptides derived from immunogenic epitopes identified through DNA and RNA sequencing of a patient's tumor cells, combined with the immunostimulant poly-ICLC with potential immunomodulating and antineoplastic activities. Vaccination with the neoantigen-based RCC vaccine stimulates the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the neoantigens, leading to tumor cell lysis. The adjuvant poly-ICLC, composed of double-stranded RNA molecules of polyinosinic-polycytidylic acid stabilized with poly L-lysine in carboxymethylcellulose, is a ligand for toll-like receptor-3 (TLR3) and induces the release of cytokines which may help to boost the immune response against the selected neoantigens.

• Neoantigen-based therapeutic cancer vaccine grt-c903 - A cancer priming vaccine consisting of tumor-specific shared neoantigens, which are immunogenic and unique across a subset of patients, with potential immunostimulating and antineoplastic activities. Upon administration of neoantigen-based therapeutic cancer vaccine GRT-C903, followed by the boosting vaccine GRT-R904, the peptides stimulate the host immune system to mount a specific cytotoxic T-lymphocyte (CTL) response against the shared neoantigens expressed on tumor cells, which results in tumor cell lysis.

• Neoantigen-based therapeutic cancer vaccine grt-r904 - A cancer boosting vaccine consisting of tumor-specific shared neoantigens, which are immunogenic and unique across a subset of patients, with potential immunostimulating and antineoplastic activities. Upon administration of the neoantigen-based therapeutic cancer vaccine GRT-R904, which is administered after the initial administration of the priming vaccine GRT-C903, the peptides stimulate the host immune system to mount a specific cytotoxic T-lymphocyte (CTL) response against the shared neoantigens expressed on tumor cells, which results in tumor cell lysis.

• Neoantigen-encoding personalized virus-2 - A personalized cancer vaccine comprised of a not yet disclosed oncolytic virus encoding tumor-specific neoantigens that have been identified through genetic sequencing of a patient's tumor cells, with potential immunostimulatory and antineoplastic activities. Upon administration, the neoantigen-encoding personalized virus-2 (PSV-2) infects cells and expresses the tumor-specific neoantigens (TSNAs). This stimulates the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the TSNAs, leading to tumor cell lysis.

• Neoantigen-hsp70 peptide cancer vaccine agen2017 - A proprietary, personalized autologous synthetic cancer vaccine composed of patient-specific synthetic cancer neo-epitopes complexed with heat shock protein 70 (HSP 70; HSP70), with potential immunostimulating and antineoplastic activities. Upon administration of the neoantigen-HSP70 peptide cancer vaccine AGEN2017, the HSPs present the neoantigens to antigen presenting cells (APCs) and help elicit a potent neoantigen-specific T-cell-based anti-tumor immune response, thereby killing the neoantigen-expressing cancer cells. HSP70 is able to the transport the neo-epitopes, activate APCs and enhance the T-cell-mediated immune response.

• Neoantigen-loaded autologous dendritic cell vaccine - A personalized, peptide-based therapeutic dendritic cell (DC) vaccine consisting of autologous DCs loaded with immunogenic peptides derived from autologous cancer cells, with potential immunomodulating and antineoplastic activities. Upon leukapheresis, mature DCs are loaded with immunogenic neoantigens. Vaccination with the neoantigen-loaded autologous DC vaccine stimulates the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the neoantigens, which results in tumor cell lysis.

• Neratinib - An orally available, 6,7-disubstituted-4-anilinoquinoline-3-carbonitrile irreversible inhibitor of the HER-2 receptor tyrosine kinase with potential antineoplastic activity. Neratinib binds to the HER-2 receptor irreversibly, thereby reducing autophosphorylation in cells, apparently by targeting a cysteine residue in the ATP-binding pocket of the receptor. Treatment of cells with this agent results in inhibition of downstream signal transduction events and cell cycle regulatory pathways; arrest at the G1-S (Gap 1/DNA synthesis)-phase transition of the cell division cycle; and ultimately decreased cellular proliferation. Neratinib also inhibits the epidermal growth factor receptor (EGFR) kinase and the proliferation of EGFR-dependent cells.

• Neratinib maleate - The maleate salt form of neratinib, an orally available, quinazoline-based, irreversible inhibitor of both the receptor tyrosine kinases (RTKs) human epidermal growth factor receptor 2 (HER2; ERBB2) and human epidermal growth factor receptor (EGFR), with potential antineoplastic activity. Upon administration, neratinib targets and covalently binds to the cysteine residue in the ATP-binding pockets of both HER2 and EGFR. This inhibits their activity and results in the inhibition of downstream signal transduction events, induces cell cycle arrest, apoptosis and ultimately decreases cellular proliferation in HER2- and EGFR-expressing tumor cells. EGFR and HER2, RTKs that are mutated or overactivated in many tumor cell types, play key roles in tumor cell proliferation and tumor vascularization.

• Nesvacumab - A fully human monoclonal antibody directed against angiopoietin 2 (ANG2) with potential antiangiogenic and antineoplastic activities. Nesvacumab binds to ANG2 and interferes with the interaction between Ang2 and its receptor TEK tyrosine kinase (Tie2), which may inhibit tumor cell angiogenesis and tumor cell proliferation. ANG2 is upregulated in a variety of cancer cell types and plays a crucial role in angiogenesis.

• Neural stem cells-expressing crad-s-pk7 - Neural stem cells (NSCs) that are transfected with the gliomatropic oncolytic adenovirus (OV) CRAd-S-pk7, a conditionally replicative oncolytic adenoviral (CRAd) vector that contains the tumor-specific survivin promoter (S) and a fiber protein polylysine modification (pk7), with potential antineoplastic activity. Upon intracerebral administration of NSC loaded with CRAd-S-pk7, the NSCs preferentially migrate towards tumor cells, and the polylysine moiety of the modified fiber protein expressed by the viral vector specifically targets and binds to tumor-specific heparan sulfate proteoglycans. Subsequently, the virus can infect the tumor cells and viral replication is initiated because E1 gene expression is controlled by the tumor-specific promoter for survivin. This results in the specific lysis of the glioma cells. The pk7 fiber modification and the survivin promoter enable tumor-specific infectivity, and transcriptional targeting and preferential replication in glioma cells, while sparing the surrounding normal brain parenchyma. The pK7 is comprised of a heparan sulfate binding domain incorporated into the fiber protein of the adenovirus.

• Ng-nitro-l-arginine - An amino acid derivative and nitric oxide synthase (NOS) inhibitor with potential antineoplastic and antiangiogenic activities. Upon administration, NG-nitro-L-arginine inhibits the enzyme nitric oxide synthase, thereby preventing the formation of nitric oxide (NO). By preventing NO generation, the vasodilatory effects of NO are abrogated leading to vasoconstriction, reduction in vascular permeability and an inhibition of angiogenesis. As blood flow to tumors is restricted, this may result in an inhibition of tumor cell proliferation. NO plays an important role in tumor blood flow and stimulation of angiogenesis, tumor progression, survival, migration and invasiveness.

• Niacinamide - The active form of vitamin B3 and a component of the coenzyme nicotinamide adenine dinucleotide (NAD). Niacinamide acts as a chemo- and radio-sensitizing agent by enhancing tumor blood flow, thereby reducing tumor hypoxia. This agent also inhibits poly(ADP-ribose) polymerases, enzymes involved in the rejoining of DNA strand breaks induced by radiation or chemotherapy.

• Niclosamide - An orally bioavailable chlorinated salicylanilide, with anthelmintic and potential antineoplastic activity. Upon oral administration, niclosamide specifically induces degradation of the androgen receptor (AR) variant V7 (AR-V7) through the proteasome-mediated pathway. This downregulates the expression of the AR variant, inhibits AR-V7-mediated transcriptional activity, and reduces AR-V7 recruitment to the prostate-specific antigen (PSA) gene promoter. Niclosamide also prevents AR-V7-mediated STAT3 phosphorylation and activation. This inhibits AR/STAT3-mediated signaling and prevents expression of STAT3 target genes. Altogether, this may inhibit growth of AR-V7-overexpressing cancer cells. The AR-V7 variant, which is encoded by contiguous splicing of AR exons 1/2/3/CE3, is upregulated in a variety of cancer cell types, and is associated with both cancer progression and resistance to AR-targeted therapies.

• Nicotinamide riboside - An orally available form of vitamin B3 and precursor of nicotinamide adenine dinucleotide (NAD+) with potential use in the treatment of chemotherapy induced peripheral neuropathy (CIPN). Upon oral administration, nicotinamide riboside (NR) is converted to nicotinamide mononucleotide by the NR kinases, nicotinamide riboside kinase 1 (NRK 1) and nicotinamide riboside kinase 2 (NRK 2), to which a second adenine is transferred by nicotinamide mononucleotide adenylyl transferase to generate NAD+. NAD+, an essential redox coenzyme, may offer protective effects against axonal injury from both mechanical and neurotoxic injury, and maintenance of NAD+ may be protective in mitochondrial disease. NR may help elevate and maintain NAD+ levels, which may ameliorate potential mechanisms implicated in the development of CIPN including mitochondrial dysfunction and peripheral nerve degeneration.

• Nidanilimab -

• Nifurtimox - A nitrofuran derivative with antiprotozoal and potential antineoplastic activities. Nifurtimox is reduced by cytosol enzymes or flavin-containing microsomal enzymes to a highly reactive nitro anion free radical; autooxidation of the nitro anion free radical generates cytotoxic superoxide anion (02-). In addition, nifurtimox-derived nitro anion free radicals may alkylate macromolecules such as nucleic acids and proteins, resulting in the disruption of their structure and function.

• Nilotinib - An orally bioavailable aminopyrimidine-derivative Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity. Designed to overcome imatinib resistance, nilotinib binds to and stabilizes the inactive conformation of the kinase domain of the Abl protein of the Bcr-Abl fusion protein, resulting in the inhibition of the Bcr-Abl-mediated proliferation of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) cells. This agent also inhibits the receptor tyrosine kinases platelet-derived growth factor receptor (PDGF-R) and c-kit, a receptor tyrosine kinase mutated and constitutively activated in most gastrointestinal stromal tumors (GISTs). With a binding mode that is energetically more favorable than that of imatinib, nilotinib has been shown to have an approximately 20-fold increased potency in kinase and proliferation assays compared to imatinib.

• Nilotinib hydrochloride anhydrous - The hydrochloride salt of nilotinib, an orally bioavailable aminopyrimidine-derivative Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity. Designed to overcome imatinib resistance, nilotinib binds to and stabilizes the inactive conformation of the kinase domain of the Abl protein of the Bcr-Abl fusion protein, resulting in the inhibition of the Bcr-Abl-mediated proliferation of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) cells. This agent also inhibits the receptor tyrosine kinases platelet-derived growth factor receptor (PDGF-R) and c-kit, a receptor tyrosine kinase mutated and constitutively activated in most gastrointestinal stromal tumors (GISTs). With a binding mode that is energetically more favorable than that of imatinib, nilotinib has been shown to have an approximately 20-fold increased potency in kinase and proliferation assays compared to imatinib.

• Nilotinib hydrochloride monohydrate - The monohydrate monohydrochloride form of nilotinib, an orally bioavailable aminopyrimidine-derivative Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity. Designed to overcome imatinib resistance resulting from Bcr-Abl kinase mutations, upon administration, nilotinib binds to and stabilizes the inactive conformation of the kinase domain of the Abl portion of the Bcr-Abl fusion protein, resulting in the inhibition of the constitutive kinase activity of Bcr-Abl protein. This inhibits the Bcr-Abl-mediated proliferation of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) cells. Nilotinib also inhibits the receptor tyrosine kinases platelet-derived growth factor receptor (PDGF-R; PDGFR), mast/stem cell growth factor receptor Kit (c-Kit), and, to a lesser extent, colony-stimulating factor 1 receptor (CSF-1R; CSF1R), and discoidin domain-containing receptor 1 (DDR1).

• Nilutamide - A synthetic, nonsteroidal agent with antiandrogenic properties. Nilutamide preferentially binds to androgen receptors and blocks androgen receptor activation by testosterone and other androgens; this agent may inhibit androgen-dependent growth of normal and neoplastic prostate cells.

• Nimesulide-hyaluronic acid conjugate ca102n - A covalently bound conjugate composed of the biological polymer sodium hyaluronate (NaHA) and the hydrophobic, cyclooxygenase 2 (COX-2) inhibitor and cytotoxic agent nimesulide (Nim), with potential antineoplastic activity. Upon intravenous administration of Nim-HA conjugate CA102N, the HA moiety targets and binds to CD44. Following endocytosis of CA102N and enzymatic degradation within the lysosomal compartment, Nim is released inside CD44-expressing tumor cells, causing Nim-mediated induction of cell cycle arrest tumor cell apoptosis and decreases tumor cell growth. In addition, Nim inhibits various tumor cell signaling pathways thereby further inhibiting tumor cell proliferation. CD44, a transmembrane glycoprotein and HA receptor expressed in healthy tissue, plays a key role in cellular growth, survival, differentiation and motility. Overexpressed in a variety of cancer cell types, CD44 plays a key role in tumor cell proliferation, migration and survival. Conjugation of HA to Nim allows for increased solubility of Nim and for targeted delivery of Nim to CD44-expressing tumor cells, thereby increasing efficacy and safety of Nim.

• Nimodipine - A dihydropyridine derivative and an analogue of the calcium channel blocker nifedipine, with antihypertensive activity. Nimodipine inhibits the transmembrane influx of calcium ions in response to depolarization in smooth muscle cells, thereby inhibiting vascular smooth muscle contraction and inducing vasodilatation. Nimodipine has a greater effect on cerebral arteries than on peripheral smooth muscle cells and myocardial cells, probably because this agent can cross the blood brain barrier due to its lipophilic nature. Furthermore, 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.

• Nimotuzumab - A humanized monoclonal antibody directed against the epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Nimotuzumab binds to and inhibits EGFR, resulting in growth inhibition of tumor cells that overexpress EGFR. This agent may act synergistically with radiation therapy.

• Nimustine - A nitrosourea with antineoplastic activity. Nimustine alkylates and crosslinks DNA, thereby causing DNA fragmentation, inhibition of protein synthesis, and cell death. (NCI05)

• Nimustine hydrochloride - The hydrochloride salt of nimustine, a nitrosourea with antineoplastic activity. Nimustine alkylates and crosslinks DNA, thereby causing DNA fragmentation, inhibition of protein synthesis, and cell death.

• Ningetinib tosylate - The tosylate salt form of ningetinib, an orally available inhibitor of the receptor tyrosine kinases c-MET/hepatocyte growth factor receptor (HGFR), vascular endothelial growth factor receptor 2 (VEGFR2 KDR), Axl (UFO), Mer, and Fms-like tyrosine kinase 3 (Flt3; CD135; STK1; FLK2), with antineoplastic activity. Upon administration, ningetinib binds to a variety of kinases, including c-Met, VEGFR2, Axl, Mer and Flt3, thereby inhibiting their signaling pathways. This inhibits growth, angiogenesis and metastasis of tumor cells that overexpress these kinases. c-Met, VEGFR2, Axl, Mer and Flt3 are overexpressed by many tumor cell types and play key roles in tumor cell proliferation, survival, invasion and metastasis.

• Nintedanib - An orally bioavailable, indolinone-derived inhibitor of multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs), with potential antiangiogenic, antifibrotic and antineoplastic activities. Upon administration, nintedanib selectively binds to and inhibits vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), and colony stimulating factor 1 receptor (CSF1R) tyrosine kinases, which may result in the induction of endothelial cell apoptosis, the reduction in tumor vasculature, the inhibition of tumor cell proliferation and migration, and antifibrotic activity in pulmonary fibrosis. In addition, nintedanib also binds to and inhibits members of the Src family of tyrosine kinases, including Src, Lck and Lyn, and fms-like tyrosine kinase 3 (FLT-3). VEGFR, FGFR, PDGFR and CSF1R RTKs play key roles in tumor angiogenesis, tumor cell proliferation and metastasis, as well as pulmonary fibrosis.

• Niraparib - An orally bioavailable inhibitor of poly (ADP-ribose) polymerase (PARP) types 1 and 2 (PARP-1 and -2), with antineoplastic activity. Upon administration, niraparib binds to and inhibits the activity of PARP-1 and -2, thereby inhibiting PARP-1 and -2-mediated DNA repair, enhancing the accumulation of DNA strand breaks, promoting genomic instability and resulting in apoptosis. The PARP family of proteins catalyzes post-translational ADP-ribosylation of nuclear proteins and is activated by single-strand DNA (ssDNA) breaks.

• Niraparib tosylate monohydrate - An orally bioavailable, hydrated, tosylate salt form of niraparib, an inhibitor of poly (ADP-ribose) polymerase (PARP) types 1 and 2 (PARP-1 and -2), with antineoplastic activity. Upon administration, niraparib binds to and inhibits the activity of PARP-1 and -2, thereby inhibiting PARP-1 and -2-mediated DNA repair, enhancing the accumulation of DNA strand breaks, promoting genomic instability and resulting in apoptosis. The PARP family of proteins catalyzes post-translational ADP-ribosylation of nuclear proteins and is activated by single-strand DNA (ssDNA) breaks.

• Nirogacestat - A selective gamma secretase (GS) inhibitor with potential antitumor activity. Nirogacestat binds to GS, blocking proteolytic activation of Notch receptors; Notch signaling pathway inhibition may follow, which may result in the induction of apoptosis in tumor cells that overexpress Notch. The integral membrane protein GS is a multi-subunit protease complex that cleaves single-pass transmembrane proteins, such as Notch receptors, at residues within their transmembrane domains. Overexpression of the Notch signaling pathway has been correlated with increased tumor cell growth and survival.

• Nitric oxide-releasing acetylsalicylic acid derivative - A nitric oxide (NO) donating derivative of acetylsalicylic acid with anti-inflammatory, analgesic, antipyretic, antithrombotic, gastroprotective and potential antitumor activities. The acetylsalicylic acid derivative moiety of this agent inhibits the activities of cyclooxygenase (COX) I and II, preventing the formation of prostaglandins and thromboxanes. A reduction in prostaglandin synthesis accounts for this agent's anti-inflammatory, anti-pyretic and analgesic activities; a reduction in thromboxane A2 synthesis results in an irreversible inhibition of platelet aggregation. NO donation by this agent, after cleavage from the acetylsalicylic acid derivative in vivo, may protect the gastric mucosa against the damaging effects of the aspirin derivative by modulating prostaglandins. In tumor cells, the NO donating moiety may block the cell cycle in the G1 and G2 phases and may induce apoptosis through caspase-mediated mechanisms.

• Nitrogen mustard prodrug pr-104 - A non-toxic, small-molecule, hypoxia-activated, 3,5-dinitrobenzamide nitrogen mustard pre-prodrug with potential antitumor activity. Upon intravenous administration, PR-104 is converted by systemic phosphatases to the alcohol intermediate PR-104A, which is reduced to form the active DNA-crosslinking mustard species hydroxylamine PR-104H intracellularly under hypoxic conditions. PR-104H specifically crosslinks hypoxic tumor cell DNA, resulting in the inhibition of DNA repair and synthesis, cell-cycle arrest, and apoptosis in susceptible hypoxic tumor cell populations while sparing normoxic tissues.

• Nitroglycerin transdermal patch - A sustained release transdermal patch containing the organic nitrate nitroglycerin, with vasodilator and potential immunomodulating activities. Upon application to the skin, nitroglycerin is continuously released from the patch and absorbed. In turn, nitroglycerin is converted into nitric oxide (NO), which activates guanylyl cyclase, increasing cyclic guanosine monophosphate concentration thus resulting in smooth muscle relaxation. In addition, activation of NO-mediated signaling pathways may inhibit hypoxia-induced tumor cell invasiveness, chemoresistance, evasion of immune cell recognition and cancer cell progression. Particularly, reactivation of NO-mediated signaling appears to inhibit the increased tumor cell shedding of the major histocompatibility complex class I chain-related (MIC) molecules MICA and MICB as is seen in hypoxic tumor environments; MIC molecules play key roles in tumor cell immune surveillance through their interaction with the C-type lectin-like NKG2D receptor on natural killer, lymphokine-activated killer and effector T cells.

• Nivolumab - A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Upon administration, nivolumab binds to and blocks the activation of PD-1, an immunoglobulin superfamily (IgSF) transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), which is overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen-presenting cells (APCs). This results in the activation of T-cells and cell-mediated immune responses against tumor cells. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity.

• Nk cell-enriched donor lymphocytes - A preparation of donor-derived lymphocytes that are enriched for donor-derived natural killer (NK) cells, with direct tumor cytotoxic activity. Following allogeneic stem cell transplantation and subsequent infusion of the NK cell-enriched donor lymphocytes, these cells recognize and bind to tumor cells, upon which they secrete and release perforins, granzymes, and cytokines, which results in cancer cell lysis. Infusion of donor lymphocytes is limited by the risk of graft-versus-host disease (GVHD) and NK cells normally constitute only a small portion of circulating lymphocytes. Therefore, NK cell-enrichment may result in higher amounts of NK cells per infusion and improved anti-tumor immunity without increasing the risk of GVHD.

• Nlrp3 agonist bms-986299 - A nucleotide-binding domain and leucine-rich repeat (NLR) family pyrin domain containing 3 (NLRP3; NACHT, LRR and PYD Containing Protein 3; NALP3) agonist with potential immunomodulatory and antineoplastic activities. Upon administration, NLRP3 agonist BMS-986299 binds to and activates NLRP3, potentially promoting NLRP3 inflammasome-mediated secretion of interleukin-8 (IL-8), which may induce tumoricidal activity of natural killer (NK) cells against tumor cells. NLRP3, a sensor component of the NLRP3 inflammasome plays a significant role in immunity and inflammation, and may protect against tumorigenesis in some cancers.

• N-methylformamide - A water-soluble organic solvent. As an adjuvant antineoplastic agent, N-methylformamide depletes cellular glutathione, a key molecule involved in the antioxidation of reactive oxygen species (ROS) and other free radicals, thereby enhancing ionizing radiation-induced DNA cross-linking in and terminal differentiation of tumor cells.

• Nocodazole - A synthetic tubulin-binding agent with antineoplastic activity. Nocodazole binds to beta-tubulin and disrupts microtubule assembly/disassembly dynamics. This prevents mitosis and induces apoptosis in tumor cells. Although nocodazole binding site overlaps with that of colchicine, the two agents are structurally quite different.

• Nogalamycin - An anthracycline antineoplastic antibiotic isolated from the bacterium Streptomyces nogalater. Nogalamycin intercalates into DNA and interacts with topoisomerase I, thereby inhibiting DNA replication and repair and RNA and protein synthesis.

• Nogapendekin alfa - A fusion protein complex composed of a mutated form of the cytokine interleukin (IL)-15 (IL-15N72D) and a soluble, dimeric IL-15 receptor alpha (IL-15Ra) Fc fusion protein (IL-15Ra-Fc) (IL-15N72D/IL-15Ra-Fc), with potential antineoplastic activity. Upon administration, superagonist interleukin-15:interleukin-15 receptor alphaSu/Fc fusion complex N-803 binds to the IL-2/IL-15 receptor beta-common gamma chain (IL-2Rbetagamma) receptor on natural killer (NK) and CD8+ T lymphocytes, which activates and increases the levels of NK cells and memory CD8+(CD44high) T-cells. The memory T-cells enhance the secretion of the cytokine interferon-gamma (IFN-g), which further potentiates the immune response against tumor cells. This may increase tumor cell killing and decrease tumor cell proliferation. IL-15 regulates CD8+ T and NK cell development, activation and proliferation. By coupling IL-15 to IL15Ra-Fc, this agent has a prolonged drug half-life and shows an increased ability to bind IL-2Rbetagamma, which enhances its immune stimulatory activity as compared to IL-15 alone.

• Nolatrexed dihydrochloride - The dihydrochloride salt of nolatrexed, a water-soluble lipophilic quinazoline folate analog with antineoplastic activity. Nolatrexed occupies the folate binding site of thymidylate synthase, resulting in inhibition of thymidylate synthase activity and thymine nucleotide synthesis with subsequent inhibition of DNA replication, DNA damage, S-phase cell cycle arrest, and caspase-dependent apoptosis. This agent also exhibits radiosensitizing activity.

• Non-small cell lung cancer mrna-derived vaccine cv9201 - A non-small cell lung cancer (NSCLC) vaccine containing modified mRNAs encoding cancer-testis antigen NY-ESO-1, melanoma-associated antigens C1 (MAGE-C1/CT7) and C2 (MAGE-C2/CT10), survivin, and the oncofetal antigen 5T4 with potential antitumor and immunomodulatory activities. Upon subcutaneous administration, non-small cell lung cancer mRNA-derived vaccine CV9201 may stimulate the immune system to mount a cytotoxic, antigen-specific T lymphocyte response (CTL) against NSCLC cells. The modified mRNAs in this vaccine are taken up by cells after injection and exhibit enhanced translational potency. The five tumor-associated antigens (TAAs) encoded by these mRNAs are frequently expressed by NSCLC cells.

• Norgestrel - A synthetic progestin commonly used alone or in combination with an estrogen for contraception. Norgestrel suppresses the secretion of luteinizing and follicle-stimulating hormones (LH and FSH), thickens cervical mucus, and slows the transit of ova through the fallopian tubes. This agent also exhibits antiproliferative activity in endometrial tissue and may exhibit chemopreventive and antineoplastic activities in endometrial carcinoma.

• North american ginseng extract afx-2 - An orally available proprietary aqueous extract from the North American ginseng (Panax quinquefolius) dried root, primarily containing poly-furanosyl-pyranosyl-saccharides, with potential immunostimulating activity. Upon administration, North American ginseng extract AFX-2 may stimulate the proliferation and activation of B-lymphocytes and stimulates IgG production by B cells. Also, this agent induces maturation of dendritic cells, induces T cell proliferation and activates peritoneal exudate macrophages leading to an increase in the production of the cytokines interleukin -1 and -6, tumor necrosis factor-alpha, interferon-gamma and nitric oxide.

• Nortopixantrone - A 9-aza-anthrapyrazole-based antineoplastic antibiotic. Nortopixantrone intercalates into DNA, induces single- and double-stranded DNA breaks and inhibits topoisomerase II, thereby inhibiting DNA replication and repair as well as RNA and protein synthesis. Nortopixantrone is less cardiotoxicity than anthracyclines.

• Noscapine - A phthalide isoquinoline non-narcotic alkaloid derived from the opium poppy Papaver somniferum, with mild analgesic, antitussive, and potential antineoplastic activities. Noscapine exerts its antitussive effects through the activation of sigma opioid receptors. This agent appears to exert its antimitotic effect by binding to tubulin, resulting in a disruption of microtubule assembly dynamics and subsequently, the inhibition of mitosis and tumor cell death.

• Noscapine hydrochloride - The orally available hydrochloride salt of the opioid agonist noscapine, a phthalideisoquinoline alkaloid derived from the opium poppy Papaver somniferum, with mild analgesic, antitussive, and potential antineoplastic activities. Noscapine binds to tubulin and alters its conformation, resulting in a disruption of the dynamics of microtubule assembly (by increasing the time that microtubules spend idle in a paused state) and subsequently, the inhibition of mitosis and tumor cell death. Unlike other tubulin inhibitors such as the taxanes and vinca alkaloids, noscapine does not affect microtubule polymerization.

• Notch signaling inhibitor pf-06650808 -

• Notch signaling pathway inhibitor mk0752 - A synthetic small molecule with potential antineoplastic activity. MK0752 inhibits the Notch signaling pathway, which may result in induction of growth arrest and apoptosis in tumor cells in which the Notch signaling pathway is overactivated. The Notch signaling pathway plays an important role in cell-fate determination, cell survival, and cell proliferation.

• Nsclc antigen-loaded dendritic cell-derived exosomes - Exosomes loaded with non-small cell lung cancer (NSCLC)-specific antigens, with potential immunostimulating and antineoplastic activities. Exosomes derived from autologous maturing dendritic cells (DCs) are pulsed with HLA-DP04-restricted MAGE-3, and HLA-A02-restricted peptides NY-ESO-1, MAGE-1, MAGE-3, and MART-1. Upon vaccination, these exosomes may stimulate natural killer (NK) cell activation and proliferation, restoration of NKG2D expression on NK cells, and antigen-specific T-cell responses. This may eventually lead to inhibition of tumor cell proliferation in NSCLC expressing these specific tumor antigens. These exosomes, nanovesicles secreted from DCs, are embedded with molecules necessary for potent immune responses on the exosomal surface, such as MHC class II molecules, CD40, ICAM-1, IL-15Ralpha, and NKG2D ligands.

• Nucleolin antagonist ipp-204106n - A synthetic, multivalent, lysine-rich, pseudopeptide and nucleolin antagonist with potential anti-angiogenic, antineoplastic and pro-apoptotic activities. Upon administration, IPP-204106N antagonizes nucleolin leading to a downregulation of cell-surface nucleolin; preventing the binding of certain growth promoting ligands to nucleolin may suppress tumor cell proliferation and angiogenesis. In addition, IPP-204106N is able to translocate to the nucleolus and bind to nucleolar nucleolin. This prevents nucleolin from binding to and stabilizing mRNA of the anti-apoptotic Bcl2; destabilizing Bcl2 mRNA leads to a reduction in Bcl2 protein synthesis and induces apoptosis. Further, this agent can antagonize nucleophosmin. Nucleolin, a nucleolar phosphoprotein, is overexpressed on the cell surface of certain cancer cells and binds ligands involved in cell proliferation, adhesion and angiogenesis.

• Nucleoside analog dfp-10917 - A deoxycytosine analog with potential antineoplastic activity. Upon administration, DFP-10917 is phosphorylated to generate its nucleotide form that functions as a deoxycytosine mimic and is incorporated into DNA in tumor cells. This causes DNA strand breaks during polymerization due to beta-elimination during the fidelity checkpoint, which results in G2/M phase-arrest and tumor cell apoptosis.

• Nucleotide analogue gs 9219 - A prodrug of the acyclic nucleoside phosphonate analogue 9-(2-phosphonylmethoxyethyl)guanine (PMEG) with potential antineoplastic activity. Formulated to selectively accumulate in lymphocytes, nucleotide analogue GS 9219 is converted to its active metabolite, PMEG diphosphate (PMEGpp), via enzymatic hydrolysis, deamination, and phosphorylation; subsequently, PMEGpp is incorporated into nascent DNA chains by DNA polymerases, which may result in the termination of DNA synthesis, S-phase cell cycle arrest, and the induction of apoptosis in susceptible lymphoma cell populations.

• Numidargistat - An orally available inhibitor of arginase, a manganese-dependent enzyme that hydrolyzes the amino acid arginine to form ornithine and urea, with potential immunomodulating and antineoplastic activities. Upon administration, numidargistat inhibits the breakdown of arginine by arginase, which is produced by myeloid cells, and restores arginine levels. This allows arginine to stimulate the synthesis of nitric oxide and the secretion of pro-inflammatory cytokines and chemokines, which induces the proliferation and activation of T-cells. Therefore, this agent may prevent the immunosuppressive effects of tumor-infiltrating myeloid cells and promote lymphocyte-mediated immune responses against tumor cells. Arginase is produced by neutrophils, macrophages and myeloid-derived suppressor cells (MDSC) and plays a role in inflammation-associated immunosuppression.

• Nurulimab - A monoclonal antibody directed against the human T-cell-expressed receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA4; CTLA-4), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, nurulimab targets and binds to CTLA-4 expressed on T-cells and inhibits the CTLA-4-mediated downregulation of T-cell activation. This leads to a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. CTLA-4, an inhibitory receptor and member of the immunoglobulin superfamily (IgSF), plays a key role in the downregulation of the immune system.

• Nutlin-3a - A small molecule and MDM2 (murine double minute 2) inhibitor, with potential antineoplastic activity. In cancer cells, nutlin-3a antagonizes the binding of MDM2 to p53, thereby preventing MDM2-mediated p53 degradation. This results in stabilizing and activating p53-dependent cell cycle arrest and apoptosis. The protein MDM2, a negative regulator of p53 activity, is overexpressed in many cancer cell types; the tumor suppressor p53 is mutated or deleted in about 50% of all cancers but active in the other 50%.

• Nutraceutical tbl-12 - An orally available nutritional supplement and proprietary formulation containing extracts from the sea cucumber, sea sponge, shark fin, sea urchin and the marine grass Sargassum, with potential antioxidant, antitumor, anti-angiogenic and immunomodulating activities. TBL-12 contains various amino acids, minerals, vitamins and omega-3 fatty acids.

• Ny-eso-1 peptide vaccine - A cancer vaccine consisting of an immunogenic peptide derived from the cancer-testis antigen (NY-ESO-1), an antigen found in normal testis and various tumors. Vaccination with NY-ESO-1 peptide vaccine may stimulate the host immune system to mount a humoral and cytotoxic T lymphocyte (CTL) response to cells expressing NY-ESO-1 antigen, resulting in tumor cell lysis.

• Ny-eso-1 plasmid dna cancer vaccine ppjv7611 - A plasmid DNA encoding an immunogenic peptide derived from the cancer-testis antigen NY-ESO-1 with potential immunostimulating and antitumor activities. Upon administration, NY-ESO-1 plasmid DNA cancer vaccine pPJV7611 may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells expressing the NY-ESO-1 antigen, resulting in tumor cell lysis. NY-ESO-1 is a tumor associated antigen (TAA) found in normal testes and expressed on the surfaces of various tumor cells, including melanoma, breast, bladder, prostate, lung, ovarian, and hepatocellular tumor cells.

• Ny-eso-1 protein vaccine plus montanide isa-51 vg - A cancer vaccine consisting of an immunogenic peptide derived from the cancer-testis antigen (NY-ESO-1) and emulsified in the immunoadjuvant Montanide ISA-51 VG, with potential immunomodulating and antineoplastic activities. Upon subcutaneous vaccination, the NY-ESO-1 protein vaccine emulsified in Montanide ISA-51 VG may stimulate the host immune system to mount a humoral and cytotoxic T lymphocyte (CTL) response against tumor cells expressing the NY-ESO-1 antigen, resulting in tumor cell lysis. NY-ESO-1, an antigen found in normal testes and various tumors, including bladder, breast, hepatocellular, melanoma, and prostate cancers. The surfactant mannide monooleate in Montanide ISA 51 VG is derived from vegetable-grade (VG) oleic acid that was purified from olive oil.

• Ny-eso-1 protein/microparticle mdp/bacterial dna-containing mis416 vaccine - A combination preparation composed of a protein derived from the human tumor-associated antigen (TAA) cancer-testis antigen 1 (NY-ESO-1) and a microparticle combining two immune-modifying components derived from the bacterium Propionibacterium acnes, a bacterial cell wall component that is rich in muramyl dipeptide (MDP) and bacteria-derived single-stranded DNA fragments, with potential immunomodulating, immunoadjuvant and antineoplastic activities. Upon administration of NY-ESO-1 protein/microparticle MDP/bacterial DNA-containing MIS416 vaccine, MIS416 localizes in and is taken up mainly by the liver, thereby forming a liver depot. MIS416 is then taken up by immune cells, such as monocytes and dendritic cells (DCs), where MDP and the bacterial DNA target and bind to the cytosolic innate pattern recognition receptors (PRRs) nucleotide-binding oligomerization domain-containing protein 2 (NOD2), and toll-like receptor 9 (TLR9), respectively. The simultaneous binding and activation of both NOD2 and TLR9, leads to activation of both NOD2 and TLR9 signaling pathways. This stimulates the innate immune system, induces secretion of cytokines, particularly interferon (IFN), and modulates the activation of various immune cells. In the presence of the NY-ESO-1 peptide, MIS416 enhances the cytotoxic T-lymphocyte (CTL)-mediated immune response against NY-ESO-1, resulting in an increased anti-tumor immune response. NY-ESO-1 is expressed in normal testes and on the surfaces of various tumor cells, and plays a key role in tumor cell proliferation and survival.

• Ny-eso-1 reactive tcr retroviral vector transduced autologous pbl - Human autologous peripheral blood lymphocytes (PBLs) transduced with a retroviral vector encoding a T cell receptor (TCR) specific for the cancer-testis antigen NY-ESO-1, with potential antineoplastic activity. Upon isolation, transduction, expansion ex vivo, and reintroduction into the patient, the NY-ESO-1 reactive TCR-transduced autologous PBLs bind to NY-ESO-1-overexpressing tumor cells. This may result in a specific cytotoxic T-lymphocyte (CTL) killing of NY-ESO-1-positive cancer cells. NY-ESO-1, a tumor associated antigen (TAA), is found in normal testis and on the surface of various tumor cell types; the TCR is specific for NY-ESO-1:157-165.

• Ny-eso-1(157-165) peptide-pulsed autologous dendritic cell vaccine - A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with a peptide derived from the tumor associated antigen human cancer-testis antigen NY-ESO-1 (NY-ESO-1(157-165)), with potential immunostimulatory and antineoplastic activities. Upon administration, the NY-ESO-1(157-165) peptide-pulsed autologous dendritic cell vaccine may stimulate the immune system to mount both an anti-tumoral cytotoxic T-lymphocyte (CTL)- and an antibody-mediated immune response against NY-ESO-1-expressing tumor cells, which may result in tumor cell lysis. NY-ESO-1 is expressed both in normal testes and on the surfaces of various tumor cells, and plays a key role in tumor cell proliferation and survival.

• Ny-eso-1/gla-se vaccine id-g305 - A cancer vaccine composed of a recombinant form of the tumor antigen NY-ESO-1 and glucopyranosyl lipid adjuvant (GLA)-stable emulsion (GLA-SE), with potential antineoplastic and immunomodulating activities. Upon intramuscular injection, the adjuvant portion of the NY-ESO-1/GLA-SE vaccine ID-G30 binds to toll-like receptor subtype 4 (TLR-4) expressed on dendritic cells (DCs), monocytes, macrophages and B cells. The activated DCs present the NY-ESO-1 antigen to Th1 CD4 T-lymphocytes. This leads to the induction of cytotoxic T lymphocytes (CTLs) and the killing of NY-ESO-1-expressing tumor cells. This vaccine also induces specific antibody responses and increases the production of inflammatory cytokines.

• Ny-eso-1/lage-1 peptide vaccine - A cancer vaccine containing HLA class I- and II-binding peptides derived from the NY-ESO-1/LAGE-1 cancer/testis antigen with potential immunostimulatory and antineoplastic activities. Upon administration, NY-ESO-1/LAGE-1 HLA class I/II peptide vaccine may induce a cytotoxic immune response against tumor cells that over-express NY-ESO-1/LAGE-1. Rarely expressed by normal cells, the NY-ESO-1/LAGE-1 cancer/testis antigen has been shown to be preferentially expressed on the surface of some cancer cell types.

• Ny-eso-1/mage-a4/prame/survivin/ssx2-specific autologous cytotoxic t lymphocytes - A preparation of autologous cytotoxic T-lymphocytes (CTL) that are specifically reactive to five tumor-associated antigens (TAAs), cancer-testis antigen NY-ESO-1, melanoma-associated antigen 4 (MAGE-A4), preferentially expressed antigen in melanoma (PRAME), survivin and synovial sarcoma X breakpoint 2 (SSX2; cancer/testis antigen 5.2; CT5.2), with potential antineoplastic activity. Autologous peripheral blood mononuclear cells (PBMCs) are collected and exposed ex vivo to autologous dendritic cells (DCs) that are pulsed with pepmixes, which contain overlapping peptide libraries (15 mers overlapping by 11 amino acids) spanning the entire sequence of each of the five target antigens, and simultaneously treated with the Th1-polarizing and pro-proliferative cytokines interleukin (IL) 6 (IL-6), IL-7, IL-12 and IL-15. The treated cells are expanded in culture with IL-2 and IL-15. Upon administration of the NY-ESO-1/MAGE-A4/PRAME/survivin/SSX2-specific autologous CTLs, these cells target tumor cells expressing these TAAs, which leads to cell lysis and inhibition of cell proliferation. These five TAAs are upregulated in a variety of tumor cells and play key roles in tumor cell proliferation and survival, but are absent or minimally expressed on normal, healthy human cells.

• Ny-eso-1/mart-1 peptide-pulsed dendritic cell vaccine - A cell-based cancer vaccine composed of dendritic cells (DC) pulsed with peptides derived from the tumor-associated antigens human cancer/testis antigen NY-ESO-1 and melanoma antigen recognized by T-cells (MART-1/Melan-A), with potential immunostimulatory and antineoplastic activities. Upon administration, the NY-ESO-1/MART-1-peptide pulsed DC vaccine may stimulate the immune system to mount an anti-tumor cytotoxic T-lymphocyte (CTL) response against NY-ESO-1/MART-1-expressing tumor cells, which may result in tumor cell lysis. NY-ESO-1 is expressed both in normal testes and on the surfaces of various tumor cells. MART-1 is expressed by melanoma cells.

• Ny-eso-1/prame/mage-a3/wt-1 peptide vaccine - A peptide-based cancer vaccine comprised of synthetic peptides derived from the cancer-testis antigen NY-ESO-1, preferentially expressed antigen in melanoma (PRAME), human melanoma antigen A3 (MAGE-A3) and the human Wilms tumor protein-1 (WT-1), with potential immunostimulating and antineoplastic activities. Upon administration, NY-ESO-1/PRAME/MAGE-A3/WT-1 peptide vaccine may stimulate the immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing NY-ESO-1, PRAME, MAGE-A3 and WT-1, resulting in tumor cell lysis. The NY-ESO-1, PRAME, MAGE-A3 and WT-1 peptides, tumor-associated antigens (TAAs) overexpressed in a variety of cancer cell types, play a key role in tumor cell proliferation.

• Ny-eso-1b peptide vaccine - A recombinant nonapeptide used as an antineoplastic vaccine. NY-ESO-1b peptide vaccine contains the amino acid sequence SLLMWITQC, derived from the cancer-testis tumor antigen (NY-ESO-1), which is expressed on tumor cells of many different types, including melanomas. Vaccination with this peptide vaccine may elicit strong humoral and cellular immune responses to NY-ESO-1-expressing cancers.

• Ny-eso-1-specific cd4-positive t lymphocytes - A preparation of autologous CD4+ T-lymphocytes sensitized to cancer-testis antigen NY-ESO-1, with potential immunostimulating and antineoplastic activities. CD4-positive T-lymphocytes are exposed to a NY-ESO-1 peptide ex vivo, expanded, and introduced into the patient. The NY-ESO-1-specific CD4-positive T-lymphocytes may stimulate the host immune system to produce a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the NY-ESO-1 antigen, which results in tumor cell lysis. NY-ESO-1, an antigen found in normal testis, may be upregulated in various cancers.

• Ny-eso-1-specific tcr gene-transduced t lymphocytes tbi-1301 - Human peripheral blood T-lymphocytes transduced with a retroviral vector encoding a T-cell receptor (TCR) specific for the cancer-testis antigen NY-ESO-1, with potential antineoplastic activity. Following leukapheresis, isolation of lymphocytes, expansion ex vivo, transduction, and introduction into the patient, the NY-ESO-1-specific TCR gene-transduced T lymphocytes TBI-1301 bind to NY-ESO-1 on tumor cells. This may result in cytotoxic T-lymphocyte (CTL)-mediated elimination of NY-ESO-1-positive cancer cells. NY-ESO-1, a tumor-associated antigen (TAA), is found in normal testis and on the surface of various tumor cell types.

• Ny-eso-b - A tumor-associated antigen belonging to the family of immunogenic testicular proteins that are aberrantly expressed in human cancers in a lineage-nonspecific fashion. Reverse transcription-PCR analysis showed NY-ESO-1 mRNA expression in a variable proportion of a wide array of human cancers, including melanoma, breast cancer, bladder cancer, prostate cancer, and hepatocellular carcinoma; and restricted expression in normal tissues, with high-level mRNA expression found only in testis and ovary tissues. The gene for NY-ESO-1 maps to Xq28 and codes for an 18-kDa protein having no homology with any known protein. NY-ESO-1 elicits a strong, integrated humoral and cellular immune response in a high proportion of patients with NY-ESO-1-expressing tumors and is under investigation as a cancer immunotherapy agent.

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