Corticotropin-releasing factor receptors in GtoPdb v.2025.3

Abstract

Corticotropin-releasing factor (CRF, nomenclature as agreed by the NC-IUPHAR subcommittee on Corticotropin-releasing Factor Receptors [35]) receptors are activated by the endogenous peptides corticotrophin-releasing hormone, a 41 amino-acid peptide, urocortin 1, 40 amino-acids, urocortin 2, 38 amino-acids and urocortin 3, 38 amino-acids. CRF₁ and CRF₂ receptors are activated non-selectively by CRH and UCN. CRF₂ receptors are selectively activated by UCN2 and UCN3. Binding to CRF receptors can be conducted using radioligands [¹²⁵I]Tyr⁰-CRF or [¹²⁵I]Tyr⁰-sauvagine with K_d values of 0.1-0.4 nM. CRF₁ and CRF₂ receptors are non-selectively antagonized by α-helical CRF, D-Phe-CRF-(12-41) and astressin. CRF₁ receptors are selectively antagonized by small molecules NBI27914, R121919, antalarmin, CP 154,526, CP 376,395. CRF₂ receptors are selectively antagonized by antisauvagine and astressin 2B. Although selective small molecule CRF₁ receptor antagonists were not effective in treating major depressive disorder, posttraumatic stress disorder, or alcohol use disorder in clinical trials, recent phase 2 studies have found that CRF₁ receptor antagonists effectively reduce adrenocortical androgens and precursors in congentical adrenal hyperplasia [61].