AZD8542

AZD8542 (also known as 854-A) is a potent and selective small molecule inhibitor of **11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)**, developed by **AstraZeneca** for the treatment of metabolic disorders. The enzyme 11β-HSD1 plays a crucial role in glucocorticoid metabolism by converting inactive cortisone into active cortisol, primarily in the liver and adipose tissue. Elevated local cortisol levels are linked to the pathogenesis of insulin resistance, visceral obesity, and type 2 diabetes. By inhibiting 11β-HSD1, AZD8542 aims to lower intracellular cortisol concentrations, thereby improving insulin sensitivity and metabolic profiles. The drug reached Phase I clinical trials, where its safety, tolerability, and pharmacokinetics were evaluated, but development was ultimately discontinued in favor of other candidates within the same class.