a, b Structural comparison of α-MSH-bound MC1R complex (a, b), afamelanotide-bound MC1R complex (a), SHU9119-bound MC1R complex (b) and SHU9119-bound MC4R complex (PDB: 6W25; a, b). The conformational changes of W2546.48, F2576.51, and F2807.35 upon MC1R activation are emphasized. The alignment was based on the receptors and MC1R residue numbers are colored in medium purple. c Comparison of SHU9119-binding pocket in MC1R and MC4R. M1283.36 of MC1R forms steric clash with D-NalU7 and W2546.48, making SHU9119 a partial agonist for MC1R. Hydrogen bonds are shown as red dash lines.