Ispinesib

Ispinesib is a cell-permeable, allosteric inhibitor of Eg5 (Ki app = 2. 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. nM), and to reduce glioma cell invasion. InChI: InChI=1S/C30H33ClN4O2/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/h4-6,8-15,18,20,27H,7,16-17,19,32H2,1-3H3/t27-/m1/s1, InChIKey: QJZRFPJCWMNVAV-HHHXNRCGSA-N, SMILES: ClC1=CC=C(C(N(CC2=CC=CC=C2)C([C@H](N(CCCN)C(C3=CC=C(C)C=C3)=O)C(C)C)=N4)=O)C4=C1