CORT126775

CORT126775 is a novel, non-steroidal, and selective glucocorticoid receptor modulator (SGRM) being developed for the treatment of conditions associated with hypercortisolism, including type 2 diabetes and resistant hypertension, as well as for oncology applications. Developed by Corcept Therapeutics, CORT126775 is designed to effectively antagonize glucocorticoid receptor (GR) signaling while avoiding the cross-reactivity with the progesterone receptor (PR) seen in older agents like mifepristone. Preclinical studies indicate that CORT126775 can reverse metabolic symptoms such as hyperinsulinemia and hyperglycemia in high-fat diet models and potentiate the efficacy of chemotherapy in pancreatic cancer xenografts. Mechanistically, it induces a unique GR transcription complex by recruiting a distinct profile of coregulators, including gelsolin (GELS) and NCOA4, while excluding others like MED1 and KMT2C.