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

作者：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

来源：ACS Medicinal Chemistry Letters, 2012, 3(2): 135-139.

DOI：10.1021/ml200259q

• CX-6258
• Pim-1
• Pim-2
• Pim-3
• MV-4-11
• PC3

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.

• 出版日期2012-2