Biological Activity
BMS-816336 is a novel, potent and orally bioavailable inhibitor against human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme with an IC50 of 3.0 nM[1].
11β-HSD1 inhibition may be useful in the treatment of type II diabetes and other potential clinical utilities such as atheroprotection and cognitive protection. BMS-816336 (6n-2) inhibits 11β-HSD1 enzyme in HEK and 3T3L1 cells with IC50s of 37.3 and 28.6 nM, respectively[1].
BMS-816336 represents a potential new treatment for type 2 diabetes, metabolic syndrome, and other human diseases modulated by glucocorticoid control. BMS-816336 (6n-2) exhibits a robust acute pharmacodynamic effect in cynomolgus monkeys (ED50=0.12 mg/kg) and in DIO mice (1, 3, 10, 30, 100 mg/kg, 120 mintues). It is orally bioavailable (%F ranges from 20 to 72% in preclinical species) and has a predicted pharmacokinetic profile of a high peak to trough ratio and short half-life in humans[1].
References
[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.
