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.
Ligand | Binding Site | References |
|---|---|---|
| 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 | CRF2 > CRF1 | 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}.