Peptide and non-peptide CRF receptor ligands

The labels listed under the Ligand and Binding Site columns reflect International Union of Pharmacology consensus nomenclature (Hauger et al., 2003). The “small molecules” label reflects a rather large group of mechanistically related but chemically diverse nonproprietary and proprietary CRF1 receptor antagonists including antalarmin, CP-154,526, NBI 27914, R121919/NBI 30775, and so on (Zorrilla et al., 2003). The References column cites key papers relating the discovery of each respective ligand as well as a pharmacological study of efficacy.


Binding Site

Limited selectivity CRF receptor agonists
    r/hCRF CRF1, CRF2, CRF-BP Vale et al., 1981; Britton et al., 2000
    oCRF CRF1, CRF2 Sutton et al., 1995; Valdez et al., 2002a
    Urocortin 1 CRF1, CRF2, CRF-BP Vaughan et al., 1995; Macey et al., 2000
    Sauvagine CRF1, CRF2, CRF-BP Erspamer et al., 1980; Britton et al., 1984
High selectivity CRF receptor agonists
    Urocortin 2 CRF2 > CRF1 Reyes et al., 2001; Valdez et al., 2002a
    Urocortin 3 CRF2 > CRF1 Lewis et al., 2001; Valdez et al., 2003a
Nonselective CRF receptor antagonists
    α-Helical-CRF9-41 CRF1, CRF2, CRF-BP Rivier et al., 1984; Swerdlow et al., 1989
    d-Phe-CRF12-41 CRF1, CRF2 Gulyas et al., 1995; Valdez et al., 2003b
    Astressin CRF1, CRF2 Miranda et al., 1994; Spina et al., 2000
Selective CRF receptor antagonists
    Small molecules CRF1 McCarthy et al., 1999; Zorrilla et al., 2002
    Antisauvagine-30 CRF2 > CRF1 Ruhmann et al., 1998; Hammack et al., 2003
    Astressin B
Wang et al., 2001; Rivier et al., 2002
  • Antalarmin, N-butyl-N-ethyl[2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-amine; NBI 27914, 5-chloro-N-(cyclopropylmethyl)-2-methyl-N-propyl-N′-(2,4,6-trichlorophenyl)-4,6-pyrimidinediamine; R121919/NBI 30775, 3-[6-(dimethylamino)-4-methyl-pyrid-3-yl]-2,5-dimethyl-N,N-dipropyl-pyrazolo[2,3-a]pyrimidin-7-amine; astressin B, {cyclo(30-33)[d-Phe12,Nle21,CαMeLeu27,Glu30,Lys33,Nle38,CαMeLeu40]Ac-h CRF9-41}.