JTT-654

JTT-654 is an orally active, potent, and selective small molecule inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme that converts inactive glucocorticoids to their active forms in target tissues. By inhibiting 11β-HSD1 in the liver and adipose tissue, JTT-654 reduces local glucocorticoid activation, thereby ameliorating insulin resistance and improving glucose metabolism. It was developed primarily for the treatment of type 2 diabetes mellitus, with a particular focus on non-obese type 2 diabetic patients. Preclinical studies demonstrated that JTT-654 improved insulin sensitivity and glucose oxidation while reducing gluconeogenesis and glycogen storage abnormalities induced by excess glucocorticoids. The drug reached phase II clinical trials but development was discontinued[1][2][4][5].