| Identification | Back Directory | [Name]
Ispinesib | [CAS]
336113-53-2 | [Synonyms]
CS-376
SB-71599
Ispinesib
SB 715992
CK0238273
Ispinesib2
Unii-bkt5F9C2ni
Ispinesib, >=98%
SB715992 (Ispinesib)
Ispinesib (SB-715992)
ISPINESIB;SB-715992;SB715992
Ispinesib Mesilate(SB-715992)
Ispinesib (SB-715992 /CK0238273)
(R)-N-(3-Aminopropyl)-N-(1-(3-benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylpropyl
BenzaMide, N-(3-aMinopropyl)-N-((1R)-1-(7-chloro-3,4-dihydro-4-oxo-3-(phenylMethyl)-2-quinazolinyl)-2-Methylprop
(R)-N-(3-aminopropyl)-N-(1-(3-benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)-4-methylbenzamide
N-(3-Aminopropyl)-N-[(1R)-1-[7-chloro-3,4-dihydro-4-oxo-3-(phenylmethyl)-2-quinazolinyl]-2-methylpropyl]-4-methylbenzamide
Benzamide, N-(3-aminopropyl)-N-((1R)-1-(7-chloro-3,4-dihydro-4-oxo-3-(phenylmethyl)-2-quinazolinyl)-2-methylpropyl)-4-methyl-
Ispinesib
N-(3-Aminopropyl)-N-[(1R)-1-[7-chloro-3,4-dihydro-4-oxo-3-(phenylmethyl)-2-quinazolinyl]-2-methylpropyl]-4-methylbenzamide
N-(3-Aminopropyl)-N-[(1R)-1-[7-chloro-3,4-dihydro-4-oxo-3-(phenylmethyl)-2-quinazolinyl]-2-methylpropyl]-4-methylbenzamide Ispinesib(SB-715992) | [Molecular Formula]
C30H33ClN4O2 | [MDL Number]
MFCD22628831 | [MOL File]
336113-53-2.mol | [Molecular Weight]
517.06 |
| Chemical Properties | Back Directory | [Melting point ]
89 - 92°C | [Boiling point ]
708.0±70.0 °C(Predicted) | [density ]
1.21±0.1 g/cm3(Predicted) | [storage temp. ]
-20°C Freezer, Under inert atmosphere | [solubility ]
Chloroform (Slightly), Methanol (Slightly) | [form ]
Solid | [pka]
9.65±0.10(Predicted) | [color ]
White to Off-White | [optical activity]
[α]/D +315 to +375°, c =0.5 in chloroform-d |
| Hazard Information | Back Directory | [Uses]
Ispinesib is the first potent, highly specific small-molecule inhibitor of KSP tested for the treatment of human disease. Anticancer agent. | [Uses]
The kinesin-like spindle protein Eg5 (also known as kinesin-5, kinesin family protein 11, or Kif11) is a motor protein that is essential for establishing a bipolar spindle during mitosis both in normal and tumor cells. Ispinesib is a cell-permeable, allosteric inhibitor of Eg5 (Ki app = 2.3 nM) with >10,000-fold selectivity for Eg5 over a range of other mitotic kinesins. It induces a monopolar spindle phenotype, leading to the activation of a spindle assembly checkpoint, mitotic arrest, and subsequent cell death (GI50s = 22-82 nM in colon, pancreas, prostrate, and lung cancer cells in vitro). At 10 mg/kg, ispinesib produces tumor regression of breast cancer cell xenografts in mice. It has also been used to halt the growth of treatment-resistant glioblastoma tumor-initiating cells, to prevent tumor initiation and self-renewal of a cancer stem cell population (EC50 = 1.15 nM), and to reduce glioma cell invasion.[Cayman Chemical] | [Definition]
ChEBI:N-(3-aminopropyl)-N-[(1R)-1-[7-chloro-4-oxo-3-(phenylmethyl)-2-quinazolinyl]-2-methylpropyl]-4-methylbenzamide is a member of benzamides. | [Biological Activity]
ispinesib (sb-715992) is a selective inhibitor of ksp with ic50 value of 0.5 nm [1].kinesin spindle protein (ksp) is a kinesin motor protein and plays an important role in the formation of a bipolar mitotic spindle and cell cycle progression through mitosis. it has been shown that abnormal expression of ksp is correlated with a variety of human cancers and its inhibitors may be a promising anticancer agent [2] [3].ispinesib (sb-715992) is a potent ksp inhibitor and often combines with chemotherapy drugs to tumor treatment. when tested with a panel of 23 tumor cell lines, ispinesib (sb-715992) treatment showed high activity to inhibit ksp in most of the cell lines while only rh18 having an ic50 value greater than 1 μm (median ic50=4.1 nm, maximum ic50=0.5 nm) by using pptp method [1]. in a panel of 53 breast cell lines, ispinesib (sb-715992) exhibits broad antiproliferative activity and up-regulated the expression of both mitotic and apoptotic markers in mda-mb-468 cell line [2]. when tested with pc-3 cells, ispinesib (sb-715992) treatment inhibits cell proliferation, inducs cell apoptosis and up-regulated the expressions of genes that related to the control of cell proliferation, cell cycle, cell signaling pathways and apoptosis [3].in mouse model with 26 tumor cells subcutaneous xenograft, administration of ispinesib (sb-715992) inducs markedly tumor growth delay with the percent of 88% (23/26) and maintained completed response (cr) in the rhaboid tumor, wilms tumor and ewing sarcoma xenograft mouse model [1]. | [storage]
4°C, protect from light | [References]
[1]. carol, h., et al., initial testing (stage 1) of the kinesin spindle protein inhibitor ispinesib by the pediatric preclinical testing program. pediatr blood cancer, 2009. 53(7): p. 1255-63.
[2]. purcell, j.w., et al., activity of the kinesin spindle protein inhibitor ispinesib (sb-715992) in models of breast cancer. clin cancer res, 2010. 16(2): p. 566-76.
[3]. davis, d.a., et al., increased therapeutic potential of an experimental anti-mitotic inhibitor sb715992 by genistein in pc-3 human prostate cancer cell line. bmc cancer, 2006. 6: p. 22. |
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