Discovery of CX-6258. A potent, selective, and orally efficacious pan-Pim kinases inhibitor

…, A Siddiqui-Jain, L Darjania, R Stansfield…

Index: Haddach, Mustapha; Michaux, Jerome; Schwaebe, Michael K.; Pierre, Fabrice; O'Brien, Sean E.; Borsan, Cosmin; Tran, Joe; Raffaele, Nicholas; Ravula, Suchitra; Drygin, Denis; Siddiqui-Jain, Adam; Darjania, Levan; Stansfield, Ryan; Proffitt, Chris; MacAlino, Diwata; Streiner, Nicole; Bliesath, Joshua; Omori, May; Whitten, Jeffrey P.; Anderes, Kenna; Rice, William G.; Ryckman, David M. ACS Medicinal Chemistry Letters, 2012 , vol. 3, # 2 p. 135 - 139

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Citation Number: 28

Abstract

Structure–activity relationship analysis in a series of 3-(5-((2-oxoindolin-3-ylidene) methyl) furan-2-yl) amides identified compound 13, a pan-Pim kinases inhibitor with excellent biochemical potency and kinase selectivity. Compound 13 exhibited in vitro synergy with chemotherapeutics and robust in vivo efficacy in two Pim kinases driven tumor models.