AVP-28225

AVP-28225 is a selective, orally bioavailable small molecule inhibitor of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). This enzyme is primarily responsible for the intracellular conversion of inactive cortisone into the active glucocorticoid cortisol. Elevated cortisol levels in the brain have been associated with hippocampal atrophy and cognitive decline, particularly in aging and Alzheimer's disease. By inhibiting 11β-HSD1, AVP-28225 aims to reduce local cortisol concentrations in the brain, thereby potentially providing neuroprotective effects and improving cognitive function. Developed by Avanir Pharmaceuticals, the compound was investigated in early-stage clinical trials for Alzheimer's disease before development was discontinued.