TABLE 1.

Chemical structures of potent melanocortin‐4 receptor (MC4R) drug candidate examples with MC4R‐specific Ki/IC₅₀/EC50 values

Name	Type	Structure	Ki/IC50/EC50 value for MC4R	Reference
Sodium 4‐phenylbutyrate (4‐PBA)	Chemical chaperone		—	70 , 71
THIQ	Pharmacological chaperone agonist		IC50 1.2 nM	75
NPB	Pharmacological chaperone antagonist		Ki 2.4 nM	72
Ipsen 17	Pharmacological chaperone antagonist		Ki 0.96 nM	73
RO‐273225 (Butyr‐His‐D‐Phe‐Arg‐Trp‐Sar‐NH2)	Linear peptide		EC50 1 ± 0.3	113
PL‐8905	Cyclic peptide		High affinity	49
Setmelanotide	Cyclic peptide		EC50 0.27 nM	36
2Me‐2H tetrazole derivative	Nonpeptide agonists		High affinity	101
Piperazine benzenes	Nonpeptide agonists		Ki 11 nM	103
1,3,4‐trisubstituted‐2‐oxopiperazine	Nonpeptide agonists		Ki 5.7 nM	104

Abbreviations: EC₅₀, half maximum effective concentration; IC₅₀, half maximum inhibitory concentration; Ki, inhibition constant; MC4R, melanocortin‐4 receptor; THIQ, N‐[(3R)‐1,2,3,4‐Tetrahydroisoquinolinium‐3‐ylcarbonyl]‐(1R)‐1‐(4‐chlorobenzyl)‐2‐[4‐cyclohexyl‐4‐(1H‐1,2,4‐triazol‐1‐ylmethyl) piperidin‐1‐yl]‐2‐oxoethylamine.