An inhibitor of microtubule polymerization
HTI 286 is an inhibitor of microtubule polymerization.1,2 It binds to (Kd = 260 nM) and inhibits the polymerization of tubulin in a cell-free assay when used at concentrations of 0.1 and 1 ?M. HTI 286 (30 nM) induces cell cycle arrest at the G2/M phase and apoptosis in KB-3-1 epidermoid carcinoma cells.2 It inhibits cell growth in a panel of 18 tumor cell lines, including HCT-15 and DLD-1 colon cancer cells, which overexpress P-glycoprotein (mean IC50 = 2.5 nM). HTI 286 (1.6 mg/kg) reduces tumor volume in LOX, KB-3-1, KB-8-5, MX-1, DLD-1, and HCT-15 mouse xenograft models.
1.Krishnamurthy, G., Cheng, W., Lo, M.-C., et al.Biophysical characterization of the interactions of HTI-286 with tubulin heterodimer and microtubulesBiochemistry42(46)13484-13495(2003) 2.Loganzo, F., Discafani, C.M., Annable, T., et al.HTI-286, a synthetic analogue of the tripeptide hemiasterlin, is a potent antimicrotubule agent that circumvents P-glycoprotein-mediated resistance in vitro and in vivoCancer Res.63(8)1838-1845(2003)
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