BI-135585

BI-135585 is a potent, selective and orally active 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor with an IC₅₀ of 13 nM. BI-135585 exhibits >1000-fold selectivity over other hydroxysteroid dehydrogenases. BI-135585 can be used for type 2 diabetes research^[1][2]. IC50 & Target: IC50: 13 nM (11β-HSD1)^[1] In Vitro: BI-135585 binds in the substrate binding pocket of the active site of 11β-HSD1. Cellular activity of BI-135585 is examined by determining inhibition of 11β-HSD1 activity in human preadipocytes, the average IC₅₀ is 1 nM^[1].
In human adipose tissue ex vivo, BI-135585 inhibits the conversion of cortisone to cortisol with an average IC₅₀ of 11 nM^[1].
Abdominal subcutaneous and perirenal adipose tissue was harvested from one, male cynomolgus monkey. BI-135585 (20 hours) reduces enzyme activity in a dose-dependent manner with an IC50 of ~10 nM in perirenal adipose tissue and an IC50 of ~100 nM in abdominal subcutaneous adipose tissue^[1]. In Vivo: BI-135585 (compound 11j; 1-3 mg/kg; po) inhibits 67% and 90% of enzyme activity respectively in perirenal adipose tissue in cynomolgus monkey^[2].