Discovery of CX-6258. A Potent, Selective, and Orally Efficacious pan-Pim Kinases Inhibitor

Mustapha Haddach; Jerome Michaux; Michael K Schwaebe; Fabrice Pierre; Sean E O'Brien; Cosmin Borsan; Joe Tran; Nicholas Raffaele; Suchitra Ravula; Denis Drygin; Adam Siddiqui-Jain; Levan Darjania; Ryan Stansfield; Chris Proffitt; Diwata Macalino; Nicole Streiner; Joshua Bliesath; May Omori; Jeffrey P Whitten; Kenna Anderes; William G Rice; David M Ryckman

doi:10.1021/ml200259q

Discovery of CX-6258. A Potent, Selective, and Orally Efficacious pan-Pim Kinases Inhibitor

ACS Med Chem Lett. 2011 Dec 27;3(2):135-9. doi: 10.1021/ml200259q. eCollection 2012 Feb 9.

Authors

Mustapha Haddach¹, Jerome Michaux¹, Michael K Schwaebe¹, Fabrice Pierre¹, Sean E O'Brien¹, Cosmin Borsan¹, Joe Tran¹, Nicholas Raffaele¹, Suchitra Ravula¹, Denis Drygin¹, Adam Siddiqui-Jain¹, Levan Darjania¹, Ryan Stansfield¹, Chris Proffitt¹, Diwata Macalino¹, Nicole Streiner¹, Joshua Bliesath¹, May Omori¹, Jeffrey P Whitten¹, Kenna Anderes¹, William G Rice¹, David M Ryckman¹

Affiliation

¹ Cylene Pharmaceuticals Inc. , 5820 Nancy Ridge Drive, Suite 200, San Diego, California 92121, United States.

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.

Keywords: CX-6258; MV-4-11; PC3; Pim-1; Pim-2; Pim-3.