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. 2019 May 16;24(10):1892. doi: 10.3390/molecules24101892

Table 4.

Data from Nickolls et al. [31] showing impaired internalization of MC4R by small molecule agonists as compared with the peptide agonists. The general structure of these small molecules is given directly below.

graphic file with name molecules-24-01892-i003.jpg
Ligand R MC4R Binding Ki (nM) MC4R EC50 (nM)
(Intrinsic Activity)
cAMP Accumulation Calcium Mobilization Internalization
α-MSH * Acetyl-SYSMEHFRWGKPV-amide 50.1 21.4
(100) 		129
(100) 		28.8
(100)
β-MSH * DEGPYRMEHFRWGSPPKD 18.6 11.2
(83) 		174
(94) 		43.7
(118)
γ-MSH * YVMGHFRWDRFG 589 631
(80) 		>1000
(62) 		>1000
(75)
des-acetyl-α-MSH SYSMEHFRWGKPV-amide 30.2 17.4
(84) 		110
(96) 		30.2
(107)
NDP-α-MSH Acetyl-SYS(Nle)H(D-Phe)-RWGKPV-amide 3.98 1.38
(112) 		120
(80) 		7.24
(89)
THIQ graphic file with name molecules-24-01892-i004.jpg 10.7 1.32
(98) 		692
(7) 		0.81
(29) **
NBI-55886 graphic file with name molecules-24-01892-i005.jpg 9.55 331
(73) 		>1000
(40) 		3.47
(16) **
NBI-56297 graphic file with name molecules-24-01892-i006.jpg 20 129
(81) 		>1000
(23) 		7.94
(−5) **
NBI-56453 graphic file with name molecules-24-01892-i007.jpg 74.1 513
(103) 		45.7
(7) 		5.25
(27) **
NBI-58702 graphic file with name molecules-24-01892-i008.jpg 6.31 43
(110) 		2.4
(20) 		7.59
(38) **
NBI-58704 graphic file with name molecules-24-01892-i009.jpg 13.5 204
(149) 		17.8
(23) 		145
(34) **

* Endogenous melanocortin receptor-4 agonist. ** For all the small molecules, the intrinsic activity for internalization was significantly different and lower than that in the cAMP accumulation assay.