Table 1.
Selective Orthosteric Ligands for Melanocortin Receptors.
| Compound | Binding Affinities 1 IC50 (nM)a | Functional Assays cAMP EC50 (nM)b | ||||||
|---|---|---|---|---|---|---|---|---|
| MC1R | MC3R | MC4R | MC5R | MC1R | MC3R | MC4R | MC5R | |
| 1. Tyr-Val-Nle-Gly-His-D-Nal(2′)-Arg-Trp-Asp-Arg-Phe-Gly-NH2 | - | 0.84 | 2.5 | 1.0 | - | >10,000 | 24(100) | >10,000 |
| 2. c[(CH2)3CO-Gly-His-D-Phe-Arg-D-Trp-Cys(S)]-Asp-Arg-Phe-Gly-NH2 | 17 | 3,900 | NB | 1,300 | NA | 100 | NA | 1300 |
| 3. D-Phe-c[Asp-Pro-D-Phe-Arg-Trp-Lys]-NH2 | - | 3.7 | 700 | 1,100 | - | 4.9 | >10,000 | >1,000 |
| 4. Ac-Nle-c[Asp-Aba-D-Phe-Arg-Trp-Lys]-NH2 | NB | 50 | NB | 2,900 | NA | NA | NA | NA |
| 5. Ac-Nle-c[Pen-Glu-His-D-Nal(2′) –Arg-Trp-Cys]-Pro-Lys-Asp-NH2 | - | 3.0 | 750 | 94 | - | NA | NA | NA |
| 10. Ac-Nle-c[Asp-N-MeHis-D-Phe-N-MeArg-N-MeTrp-N-MeLys]-NH2 | 14 | 2,200 | NB | NB | 13 | NA | NA | NA |
a
Competitive binding of ligands vs [125I]-NDP-α-MSH;
b
Adenylate cyclase assay; NB – No binding at 10−5M ligand; NA – No activity at 10−5M ligand