Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C30H33ClN4O2.CH4O3S |
| Molecular Weight | 613.167 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CS(O)(=O)=O.CC(C)[C@@H](N(CCCN)C(=O)C1=CC=C(C)C=C1)C2=NC3=CC(Cl)=CC=C3C(=O)N2CC4=CC=CC=C4
InChI
InChIKey=MRKSDPIHUJSKRA-HZPIKELBSA-N
InChI=1S/C30H33ClN4O2.CH4O3S/c1-20(2)27(34(17-7-16-32)29(36)23-12-10-21(3)11-13-23)28-33-26-18-24(31)14-15-25(26)30(37)35(28)19-22-8-5-4-6-9-22;1-5(2,3)4/h4-6,8-15,18,20,27H,7,16-17,19,32H2,1-3H3;1H3,(H,2,3,4)/t27-;/m1./s1
| Molecular Formula | C30H33ClN4O2 |
| Molecular Weight | 517.062 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
| Molecular Formula | CH4O3S |
| Molecular Weight | 96.106 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
Ispinesib (SB-715992) is a potent, specific and reversible inhibitor of kinesin spindle protein (KSP). KSP, also known as HsEg5, is a kinesin that plays an essential role in the formation of a bipolar mitotic spindle and is required for cell cycle progression through mitosis. Ispinesib is the highly specific small-molecule inhibitor of KSP tested for the treatment of human disease. It causes mitotic arrest and growth inhibition in several human tumor cell lines and is currently being tested in multiple phase II clinical trials for treatment of the breast cancer and renal cell cancer.
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Highlights from the International Conference on Molecular Targets and Cancer Therapeutics: Discovery, Biology, And Clinical Applications, Philadelphia, PA, November 2005; ECCO 13--The European Cancer Conference, Paris, France, October 30-November 3, 2005. | 2005 Dec |
|
| Increased therapeutic potential of an experimental anti-mitotic inhibitor SB715992 by genistein in PC-3 human prostate cancer cell line. | 2006 Jan 24 |
|
| American Chemical Society--233rd National Meeting. Kinesin spindle protein inhibitors. 25-29 March 2007, Chicago, IL, USA. | 2007 May |
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| ATP-competitive inhibitors of the mitotic kinesin KSP that function via an allosteric mechanism. | 2007 Nov |
|
| Progress on kinesin spindle protein inhibitors as anti-cancer agents. | 2008 Aug |
|
| Promising novel cytotoxic agents and combinations in metastatic prostate cancer. | 2008 Jan-Feb |
|
| A phase II and pharmacokinetic study of SB-715992, in patients with metastatic hepatocellular carcinoma: a study of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG IND.168). | 2008 Jun |
|
| Phase II study of ispinesib in recurrent or metastatic squamous cell carcinoma of the head and neck. | 2008 Jun |
|
| A phase II study of ispinesib (SB-715992) in patients with metastatic or recurrent malignant melanoma: a National Cancer Institute of Canada Clinical Trials Group trial. | 2008 Jun |
|
| Conformation-dependent ligand regulation of ATP hydrolysis by human KSP: activation of basal hydrolysis and inhibition of microtubule-stimulated hydrolysis by a single, small molecule modulator. | 2008 Jun 18 |
|
| A University of Chicago consortium phase II trial of SB-715992 in advanced renal cell cancer. | 2008 Mar |
|
| A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours. | 2008 Mar 11 |
|
| Mechanism of inhibition of human KSP by ispinesib. | 2008 Mar 18 |
|
| Southwest Oncology Group phase II study of ispinesib in androgen-independent prostate cancer previously treated with taxanes. | 2008 Sep |
|
| Initial testing (stage 1) of the kinesin spindle protein inhibitor ispinesib by the pediatric preclinical testing program. | 2009 Dec 15 |
|
| A Bayesian population PK-PD model for ispinesib/docetaxel combination-induced myelosuppression. | 2009 Feb |
|
| KIF11 inhibition for glioblastoma treatment: reason to hope or a struggle with the brain? | 2009 Jun 22 |
|
| Thermodynamics of nucleotide and inhibitor binding to wild-type and ispinesib-resistant forms of human kinesin spindle protein. | 2009 Nov 24 |
|
| Functional characterisation and drug target validation of a mitotic kinesin-13 in Trypanosoma brucei. | 2010 Aug 19 |
|
| A pediatric phase I trial and pharmacokinetic study of ispinesib: a Children's Oncology Group phase I consortium study. | 2010 Dec 15 |
|
| Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer. | 2010 Jan 15 |
|
| Novel benzimidazole inhibitors bind to a unique site in the kinesin spindle protein motor domain. | 2010 Sep 28 |
|
| Discovery of (+)-N-(3-aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877), a kinesin spindle protein inhibitor and potential anticancer agent. | 2011 Oct 13 |
Patents
Sample Use Guides
Patients receive ispinesib (SB-715992) IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Route of Administration:
Intravenous
In vitro, ispinesib at concentrations of 3.3 × 10−5 to 8.5 × 10−11 mol/L inhibited proliferation of all 53 breast cell lines tested. GI50 values spanned a 100-fold range and fall between 10 and 100 nmol/L for most cell lines. (The GI50 value is the drug concentration that results in 50% growth inhibition after 72 h of drug exposure relative to control). Ispinesib exhibited no apparent specificity for histopathologic subtype (luminal A, luminal B, basal) or receptor status (HER2, ER/PR).
| Substance Class |
Chemical
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R6ZMD4UH3D
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