Stress-related disorders and nonpeptidic CRH antagonists

Corticotropin-releasing hormone (CRH, also referred to as CRF), together with its related peptides and receptors, forms a physiological system that operates virtually ubiquitously throughout the body, regulating a wide range of mental, behavioral, cardiovascular, metabolic, immune, and reproductive functions, enabling mammals to adapt under both basal and stressful conditions. Recently, Auchus et al. and Newfield et al. reported the first clinical studies on the use of crinecerfont, a novel small-molecule CRH antagonist, as an adjunctive therapy for classic congenital adrenal hyperplasia (CAH). The addition of crinecerfont expands the therapeutic options beyond standard treatment with hydrocortisone and/or fludrocortisone, enhancing both biochemical and clinical disease control. Importantly, crinecerfont holds promise as a means of reducing the adverse effects associated with chronic glucocorticoid therapy, which remain a major concern in CAH management. While these findings highlight the therapeutic potential of CRH antagonists in CAH, their broader clinical applications across other disorders remain largely unexplored.