Definition

An orally bioavailable, selective nonsteroidal antagonist of the corticotropin-releasing factor type-1 (CRF1; CRF-1) receptor, that can potentially be used to prevent excess androgen production in congenital adrenal hyperplasia (CAH). Upon oral administration, tildacerfon targets, binds to and inhibits the CRF1 receptor located in the pituitary gland. This reduces adrenocorticotropic hormone (ACTH) secretion and reduces the overproduction of adrenal androgens. CRF is a key regulator of the hypothalamic-pituitary-adrenal (HPA) axis and stimulates ACTH release from the anterior pituitary. CAH comprises a set of enzymatic defects in the cortisol synthetic pathway. A decrease in adrenal cortisol production impairs negative feedback on the HPA axis, which increases production of CRF and ACTH, the primary stimulus for cortisol and 19-carbon steroid production in the adrenal cortex.