- Industry: Government; Health care
- Number of terms: 6957
- Number of blossaries: 0
- Company Profile:
The National Cancer Institute (NCI) is part of the National Institutes of Health (NIH), which is one of 11 agencies that compose the Department of Health and Human Services (HHS). The NCI, established under the National Cancer Institute Act of 1937, is the Federal Government's principal agency for ...
An orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase Aurora A kinase with potential antineoplastic activity. Auora kinase inhibitor MLN8054 binds to and inhibits Aurora kinase A, resulting in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregration, and inhibition of cell proliferation. Aurora A localizes in mitosis to the spindle poles and to spindle microtubules and is thought to regulate spindle assembly. Aberrant expression of Aurora kinases occurs in a wide variety of cancers, including colon and breast cancers.
Industry:Pharmaceutical
An orally bioavailable, highly selective, second-generation small-molecule inhibitor of the pan-epidermal growth factor receptor (EGFR) family of tyrosine kinases (ErbB family) with potential antineoplastic activity. EGFR inhibitor PF-00299804 specifically and irreversibly binds to and inhibits human EGFR subtypes, resulting in inhibition of proliferation and induction of apoptosis in EGFR-expressing tumor cells. EGFRs play major roles in tumor cell proliferation and tumor vascularization, and are often overexpressed or mutated in various tumor cell types.
Industry:Pharmaceutical
An orally bioavailable, highly soluble phosphate prodrug of B-raf (BRAF) protein kinase with potential antineoplastic activity. BRAF inhibitor ARQ 736 is converted into its active form ARQ 680 in the presence of phosphatases. In turn, ARQ 680 selectively binds to and inhibits the activity of oncogenic B-raf, which may inhibit the proliferation of tumor cells expressing mutated B-raf gene. B-raf belongs to the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations. The valine to glutamic acid substitution at residue 600 (V600E) accounts for about 90% of BRAF gene mutations.
Industry:Pharmaceutical
An orally bioavailable, lipophilic, copper-binding, halogenated 8-hydroxyquinoline with antifungal, antiparasitic and potential antitumor activities. Clioquinol forms a stable chelate with copper (copper (II) ions), which inhibits the chymotrypsin-like activity of the proteasome; consequently, ubiquitinated proteins may accumulate in tumor cells, followed by tumor cell apoptosis and the inhibition of tumor angiogenesis. In addition, the clioquinol-copper complex appears to decrease the expression of androgen receptors (AR) in human copper-enriched prostate cancer cells. Serum levels of copper are often elevated in patients with cancer; copper chelation may inhibit copper-dependent endothelial cell proliferation and tumor secretion of angiogenic factors.
Industry:Pharmaceutical
An orally bioavailable, organic, non-steroidal small molecule targeting the androgen receptor (AR) with potential antineoplastic activity. Through a mechanism that is reported to be different from other approved AR antagonists, selective androgen receptor modulator MDV3100 inhibits the activity of prostate cancer cell ARs, which may result in a reduction in prostate cancer cell proliferation and, correspondingly, a reduction in the serum prostate specific antigen (PSA) level. AR over-expression in prostate cancer represents a key mechanism associated with prostate cancer hormone resistance.
Industry:Pharmaceutical
An orally bioavailable, second-generation hydroxamic acid-based inhibitor of histone deacetylase (HDAC) with potential antineoplastic activity. HDAC inhibitor CHR-3996 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 may 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.
Industry:Pharmaceutical
An orally bioavailable, second-generation tetrathiomolybdate analog with potnetial antiangiogenic and antineoplastic activities. SOD1 inhibitor ATN-224 selectively chelates the copper ion in copper-zinc superoxide dismutase 1 (SOD1), inhibiting SOD1 activity; this may result in a decrease in intra-cellular H2O2 levels and, in turn, increased activity of intracellular phosphatases. The ATN-224-mediated increase in phosphatase activity may interfere with the activation of multiple kinase signaling pathways required for cellular proliferation and angiogenesis. This agent has been shown to inhibit VEGF and FGF-2 signaling in endothelial cells, IGF-1, EGF, NF-kB, and integrin signaling in tumor cells, and PDGF signaling in pericytes.
Industry:Pharmaceutical
An orally bioavailable, second-generation, hydroxamic acid-based inhibitor of histone deacetylase (HDAC) with potential antineoplastic activity. HDAC inhibitor JNJ-26481585 inhibits HDAC leading to an accumulation of highly acetylated histones, which may result in an induction of chromatin remodeling; inhibition of the transcription of tumor suppressor genes; inhibition of tumor cell division; and the induction of tumor cell apoptosis. HDAC, an enzyme upregulated in many tumor types, deacetylates chromatin histone proteins. Compared to some first generation HDAC inhibitors, JNJ-26481585 may induce superior HSP70 upregulation and bcl-2 downregulation.
Industry:Pharmaceutical
An orally bioavailable, semi-synthetic lipophilic analogue of camptothecin, a quinoline alkaloid extracted from the Asian tree Camptotheca acuminate, with potential antineoplastic and antiangiogenic activities. Gimatecan binds to and inhibits the activity of topoisomerase I, stabilizing the cleavable complex of topoisomerase I-DNA, which inhibits the religation of single-stranded DNA breaks generated by topoisomerase I; lethal double-stranded DNA breaks occur when the topoisomerase I-DNA complex is encountered by the DNA replication machinery, DNA replication is disrupted, and the tumor cell undergoes apoptosis. Although the mechanism of its antiangiogenic activity has yet to be full elucidated, this agent may inhibit endothelial cell migration, tumor neovascularization, and the expression of proangiogenic basic fibroblast growth factor (bFGF).
Industry:Pharmaceutical
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.
Industry:Pharmaceutical
