title: Corticotropin-releasing factor peptide antagonists: design, characterization and potential clinical relevance.
abstract: Elusive for more than half a century, corticotropin-releasing factor (CRF) was finally isolated and characterized in 1981 from ovine hypothalami and shortly thereafter, from rat brains. Thirty years later, much has been learned about the function and localization of CRF and related family members (Urocortins 1, 2 and 3) and their 2 receptors, CRF receptor type 1 (CRFR1) and CRF receptor type 2 (CRFR2). Here, we report the stepwise development of peptide CRF agonists and antagonists, which led to the CRFR1 agonist Stressin1; the long-acting antagonists Astressin2-B which is specific for CRFR2; and Astressin B, which binds to both CRFR1 and CRFR2.This analog has potential for the treatment of CRF-dependent diseases in the periphery, such as irritable bowel syndrome.
authors.affiliation: The Salk Institute, The Clayton Foundation Laboratories for Peptide Biology, La Jolla, CA 92037, USA. Electronic address: jrivier@salk.edu.
authors.forename: Jean E
authors.initials: JE
authors.lastname: Rivier
authors.affiliation: The Salk Institute, The Clayton Foundation Laboratories for Peptide Biology, La Jolla, CA 92037, USA.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Rivier
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists; D013312:Stress, Physiological; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018019:Receptors, Corticotropin-Releasing Hormone; C120841:astressin B; C519520:cyclo(31-34)(phenylalanyl(12)-norleucyl(21,28)-glutamyl(31)-lysyl(34))acetyl-corticotropin releasing factor (4-41); D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone
keywords: Astressin; Astressin B; Astressin(2)-B; CRF antagonists; CRFR(1); CRFR(2); [DPhe(12)] CRF; h/rCRF; oCRF; α-hel CRF((9–41))