Corticotropin-releasing factor receptor 2

Class

CRF2 receptor agonist

Corticotropin-releasing factor receptor 2 (CRF2, also called CRHR2) is a cell-surface receptor belonging to the class B family of G-protein-coupled receptors. It is activated naturally by a family of peptides called urocortins, which are structurally related to corticotropin-releasing factor (CRF) itself, though CRF binds CRF2 far more weakly than it binds its sister receptor, CRF1. CRF2 is expressed in the heart, blood vessels, skeletal muscle, gastrointestinal tract, and specific brain regions involved in modulating the stress response. Biologically, activating CRF2 tends to promote cardiovascular and metabolic adaptations, including changes in heart contractility and vascular tone, suppression of appetite, and dampening of stress-related behavior, in contrast to CRF1, which principally drives the classic stress and anxiety response through the hypothalamic-pituitary-adrenal axis. A drug designed as a selective CRF2 agonist aims to capture these peripheral cardiovascular and metabolic effects, or central stress-recovery effects, while minimizing the anxiogenic and hormonal cascade associated with CRF1 activation. This selectivity rationale is central to why CRF2-directed agents are of interest in conditions such as heart failure, functional gastrointestinal disorders, and stress-related physiological dysregulation, where broader CRF-pathway stimulation would carry unwanted behavioral or endocrine consequences.