11-beta-HSD1

Class

11-beta-hydroxysteroid dehydrogenase type 1 inhibitor

11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme found in tissues such as liver, fat, brain, and eye that converts inactive cortisone into active cortisol locally, amplifying glucocorticoid signaling at the tissue level independent of how much cortisol the adrenal glands secrete. This local amplification contributes to processes such as hepatic glucose production, fat accumulation in visceral adipose tissue, and pressure regulation within the eye. Because excess local glucocorticoid exposure is implicated in metabolic disturbances including insulin resistance, central obesity, and elevated blood glucose, as well as in glaucoma, inhibiting 11β-HSD1 has been explored as a way to dampen these tissue-level effects. A key rationale for targeting this enzyme specifically, rather than blocking glucocorticoid receptors broadly or suppressing adrenal cortisol synthesis, is that it can reduce excessive local glucocorticoid activity while leaving whole-body cortisol regulation largely intact, potentially avoiding the adrenal insufficiency risks associated with more systemic glucocorticoid suppression. This mechanism has therefore been investigated across metabolic disease, ocular hypertension, and other conditions where localized glucocorticoid excess is thought to drive pathology.