U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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Showing 531 - 540 of 4343 results

7-Hydroxystaurosporine (UCN-01) is a protein kinase inhibitor which is under development as an anti-cancer agent in the USA and Japan. Although UCN-01 was originally isolated from the culture broth of Streptomyces sp. as a protein kinase C-selective inhibitor, its ultimate target as an anti-cancer agent remains elusive. As a single agent, UCN-01 exhibits two key biochemical effects, namely accumulation of cells in the G1 phase of the cell cycle and induction of apoptosis. Both these effects may be important for its anti-cancer activity. As a modulator, 7-Hydroxystaurosporine enhances the cytotoxicity of other anti-cancer drugs such as DNA-damaging agents and anti-metabolite drugs through putative abrogation of G2 and/or S phase accumulation induced by these anti-cancer agents. 7-Hydroxystaurosporine had been in phase II clinical trials Life Sciences for the treatment of T-cell lymphoma, malignant melanoma, pancreatic cancer, small cell lung cancer, acute myeloid leukemia, ovarian cancer. However, the research was either discontinued or suspended.
Status:
Investigational
Source:
INN:becatecarin [INN]
Source URL:

Class (Stereo):
CHEMICAL (ABSOLUTE)

Targets:


Rebeccamycin analog (RA, Becatecarin/ BMS 181176, rebeccamycin derivative, NSC 655649) is an antitumor antibiotic with inhibitory activity against both topoisomerase I and II, and DNA-intercalating properties. The mechanism of action of becatecarin is not exactly known, but it is thought that by inhibiting (blocking) the function of topoisomerase enzymes, it will destroy cancer cells and slow down the growth of the tumour. On 25 July 2006, orphan designation (EU/3/06/388) was granted by the European Commission to Helsinn Birex Pharmaceuticals Ltd, Ireland, for becatecarin for the treatment of cancers of the biliary tree.
Status:
Investigational
Source:
INN:dotarizine
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)

Dotarizine was developed as antimigraineur. Dotarizine inhibited the 5-HT2A response in a concentration-dependent manner. The mechanism of blockade by dotarizine of cerebral vessels contractility has three components: (i) presynaptic inhibition of noradrenaline release; (ii) blockade of postsynaptic vascular 5-HT receptors; (iii) blockade of Ca(2+)entry into the vascular smooth muscle cell cytosol. The compound does not affect the vascular receptors for noradrenaline, angiotensin II or prostaglandin F(2alpha). Dotarizine had a pronounced protective effect against electric seizures.
Status:
Investigational
Source:
NCT01107522: Phase 1 Interventional Active, not recruiting Solid Tumors, Glioblastoma, Recurrent Malignant Gliomas
(2010)
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)



Carboxyamidotriazole (L651582) is a carboxyamide-amino-imidazole compound originally developed as a coccidiostat, an antiprotozoal agent that acts upon Coccidia parasites. Carboxyamidotriazole (L651582) is an orally-active agent with potential antineoplastic activity. Carboxyamidotriazole binds to and inhibits non-voltage-operated Ca2 channels, blocking both Ca2 influx into cells and Ca2 release from intracellular stores and resulting in the disruption of calcium channel-mediated signal transduction and inhibition of vascular endothelial growth factor (VEGF) signaling, endothelial proliferation, and angiogenesis. This agent may also inhibit tumor cell growth, invasion, and metastasis.
Safingol, the synthetic L-threo-stereoisomer of endogenous (D-erythro-) sphinganine, is an inhibitor of protein kinase C and sphingosine kinase in vitro, and in some cell types has been implicated in ceramide generation and induction of apoptosis. Safingol inhibits enzymatic activity and 3H-phorbol dibutyrate binding of purified rat brain PKC (IC50 = 37.5 uM and 31uM, respectively). Inhibits human PKCα, the major overexpressed isoenzyme in MCF-7 DOXR cells (IC50 = 40 uM). Safingol enhances the cytotoxic effect of the chemotherapeutic agent Mitomycin C (MMC) in gastric cancer cells by promoting drug-induced apoptosis. Safingol is an inhibitor of SphK (Sphingosine kinase). Safingol has been shown to act synergistically with other chemotherapeutic agents and may potentiate chemotherapy drug-induced apoptosis in vitro and in vivo.
Status:
Investigational
Source:
INN:opanixil [INN]
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)

Status:
Investigational
Source:
INN:cevipabulin [INN]
Source URL:

Class (Stereo):
CHEMICAL (ABSOLUTE)

Targets:


Cevipabulin is a synthetic, water-soluble tubulin-binding agent with potential antineoplastic activity. Cevipabulin appears to bind at the vinca-binding site on tubulin but seems to act more similar to taxane-site binding agents in that it enhances tubulin polymerization and does not induce tubulin depolymerization. The disruption in microtubule dynamics may eventually inhibit cell division and reduce cellular growth.
Status:
Investigational
Source:
INN:morazone
Source URL:

Class (Stereo):
CHEMICAL (MIXED)

Morazone is is a nonsteroidal anti-inflammatory drug (NSAID), originally developed by the German pharmaceutical company Ravensberg in the 1950s. Morazone was used as a moderately strong analgesic but was discontinued due to high abuse potential
Status:
Investigational
Source:
USAN:Aclantate
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)

Aclantate is a nonsteroidal anti-inflammatory drug.
Status:
Investigational
Source:
INN:peradoxime [INN]
Source URL:

Class (Stereo):
CHEMICAL (RACEMIC)

Peradoxime is an antihypertensive agent. In normal animals, 37-48% of the radioactivity from an oral dose of labeled peradoxime or parenteral dose was excreted in the urine, and 48-50% in the feces. Biliary and urinary metabolites of peradoxime were principally found as conjugates with glucuronic acid.