GSK-923295

GSK-923295 is a special, allosteric inhibitor of centromere-associated protein-E (CENP-E) kinesin motor ATPase activity, with K_i of 3.2±0.2 nM and 1.6± 0.1 nM for human and canine, respectively. IC50 & Target: Ki: 3.2 nM (human CENP-E), 1.6 nM (canine CENP-E)^[1] In Vitro: GSK-923295 (GSK923295) is a first-in-class, specific, allosteric inhibitor of CENP-E kinesin motor function. GSK923295 is uncompetitive with both ATP and MT, inhibiting CENP-E MT-stimulated ATPase activity with a K_i of 3.2±0.2 nM and 1.6±0.1 nM for human and canine, respectively. GSK923295 inhibits release of inorganic phosphate and stabilized CENP-E motor domain interaction with microtubules^[1]. GSK923295 has broad growth inhibitory activity in a panel of 237 cancer cell lines and produces significant tumor growth-delay in 8 of the 11 mouse xenograft tumor models with IC₅₀s of 17.2 nM, 55.6 nM, 42 nM, and 51.9 nM for SW48, RKO (BRAF mutant), SW620 (KRAS mutant), and HCT116 (KRAS mutant), respectively^[2]. GSK923295 is a potent and selective small molecule inhibitor of human CENPE with a K_i of 3.2 nM. GSK923295 demonstrates broad efficacy against a panel of 19 human neuroblastoma derived cell lines with an average growth IC₅₀ of 41 nM^[3]. In Vivo: Xenografts of mice treated with GSK-923295 (GSK923295) shows significant tumor growth delay compared to the control arm (NB-EBc1 p<0.0001; NB-1643 p=0.018; NB-1691 p=0.0018)^[3].