(R)-BMS-816336

(R)-BMS-816336 (Compound 6n-1) is a potent and orally active inhibitor of human, mouse and cynomolgus monkey 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme with IC50s of 14.5 nM, 50.3 nM and 16 nM, respectively [1].

Signaling Pathways >> Others >> Others

Research Areas >> Metabolic Disease

IC50: 14.5 nM (Human 11β-HSD1), 50.3 nM (Mouse 11β-HSD1) and 16 nM (Cynomolgus monkey 11β-HSD1)[1]

During the in vivo studies of BMS-816336 (Compound 6n-2) in animals, its enantiomer (R)-BMS-816336 (Compound 6n-1) in the plasma samples, together with trace amount of Ketone A are detected. The interconversion of BMS-816336 and (R)-BMS-816336 take place via the intermediate Ketone A through physiological oxidation and reduction process. In vivo studies in rat, dog, and cynomolgus monkey, the plasma ratios of (R)-BMS-816336/BMS-816336 decrease in the order: dog ≫ rat >cynomolgus monkey[1].

[1]. Ye XY, et al. Discovery of Clinical Candidate 2-((2S,6S)-2-Phenyl-6-hydroxyadamantan-2-yl)-1-(3'-hydroxyazetidin-1-yl)ethanone [BMS-816336], an Orally Active Novel Selective 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor. J Med Chem. 2017 Jun 22;60(12):4932-4948.