Tildacerfont is an investigational small molecule inhibitor of the corticotropin-releasing factor receptor 1 (CRF1). It is primarily studied for its potential in treating congenital adrenal hyperplasia (CAH), particularly the classic form caused by 21-hydroxylase deficiency. In CAH, the overactivation of the hypothalamic-pituitary-adrenal (HPA) axis leads to elevated adrenocorticotropic hormone (ACTH) levels, which in turn causes adrenal hyperplasia and overproduction of androgens. By blocking CRF1, tildacerfont aims to reduce ACTH-driven adrenal androgen excess, addressing a key driver of the disease.

Clinical development has focused on using tildacerfont as an add-on therapy to standard glucocorticoid treatment. The goal is to improve hormone control while potentially allowing for reduced glucocorticoid doses, thereby minimizing long-term side effects such as weight gain, metabolic complications, and bone loss. Early-phase trials have shown reductions in androgen levels and improvements in hormone profiles, supporting its role in better disease management. Tildacerfont represents a targeted, non-steroidal approach to modulating the HPA axis in CAH, offering a novel therapeutic strategy still under investigation.