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.
Mustapha Haddach  1 ,  Jerome Michaux  1 ,  Michael K Schwaebe  1 ,  Fabrice Pierre  1 ,  Sean E O'Brien  1 ,  Cosmin Borsan  1 ,  Joe Tran  1 ,  Nicholas Raffaele  1 ,  Suchitra Ravula  1 ,  Denis Drygin  1 ,  Adam Siddiqui-Jain  1 ,  Levan Darjania  1 ,  Ryan Stansfield  1 ,  Chris Proffitt  1 ,  Diwata Macalino  1 ,  Nicole Streiner  1 ,  Joshua Bliesath  1 ,  May Omori  1 ,  Jeffrey P Whitten  1 ,  Kenna Anderes  1 ,  William G Rice  1 ,  David M Ryckman  1
Affiliations
  • 1. Cylene Pharmaceuticals Inc. , 5820 Nancy Ridge Drive, Suite 200, San Diego, California 92121, United States.
PMID: 24900437 DOI: 10.1021/ml200259q
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.