crinetics pipeline

ACTH Antagonist

For the Treatment of Cushing’s Disease

We have an ongoing discovery effort to identify and advance into development the first nonpeptide product candidate to antagonize the peptide adrenocorticotrophic hormone, or ACTH, designed for the treatment of Cushing’s disease. Cushing’s disease results from a pituitary tumor that secretes excess ACTH, which in turn causes the downstream synthesis and over-secretion of cortisol by the adrenal glands. Cortisol is the body’s main stress hormone and excess amounts can cause significant increases in mortality and morbidity. Cushing’s disease is an orphan indication with a prevalence of approximately 13,000 patients in the United States.

ACTH acts through a peptide GPCR called the melanocortin type 2 receptor, or MC2, that is specifically expressed in the adrenal gland. Our discovery team has identified potent, selective nonpeptide antagonists of MC2 designed to block ACTH action and prevent its excessive stimulation of the adrenal gland in Cushing’s disease patients. We are advancing new molecules through preclinical activities with the goal of selecting our first product candidate for Cushing’s Disease.

Scientific Presentation

Nonpeptide, Orally Bioavailable ACTH Antagonists: Suppression of ACTH-induced
Corticosterone Secretion and Adrenal Hypertrophy in Rats

Ana Karin Kusnetzow, Melissa A. Fowler, Jon Athanacio, Greg Reinhart, Elizabeth Rico-Bautista, Sangdon Han, Sun Hee Kim, Michael Johns, Taylor A. Kredel, Julie Nguyen, Christine Staley, Hannah Tan, Rosa Luo, Stacy Markison, Ajay Madan, Yun Fei Zhu, R. Scott Struthers, and Stephen F. Betz. ENDO 2019. March 23-26, 2019; New Orleans.