TABLE 4

Comparison of cell surface expression and signaling efficacy for each compound

Cells expressing WT or mutant hMC4Rs were preincubated in the absence or presence of 10 μM concentrations of the indicated compound for 12 h. After washes, cells expressing WT or mutant hMC4Rs were stimulated for 15 min at 37°C with 100 nM NDP-α-MSH.

Parameters and Mutations	Untreated	MTHP	PPPone	MPCI	DCPMP	NBP
Surface expression
WT	100	172 ± 7	135 ± 6	144 ± 10	189 ± 34	192 ± 38
S58C	40 ± 5	102 ± 4	108 ± 4	74 ± 17	184 ± 31	229 ± 20
E61K	26 ± 3	37 ± 3	73 ± 16	42 ± 7	111 ± 2	73 ± 9
N62S	18 ± 8	47 ± 9	130 ± 32	37 ± 9	165 ± 19	138 ± 23
I69T	34 ± 11	63 ± 16	171 ± 39	63 ± 7	115 ± 17	97 ± 8
I125K	105 ± 8	204 ± 9	114 ± 16	89 ± 13	186 ± 11	217 ± 4
T162I	21 ± 2	61 ± 17	132 ± 23	74 ± 10	134 ± 8	113 ± 17
R165Q	16 ± 4	208 ± 32	344 ± 31	88 ± 15	278 ± 29	277 ± 34
R165W	16 ± 5	86 ± 5	104 ± 10	116 ± 12	283 ± 20	294 ± 16
C271Y	24 ± 3	26 ± 0.5	59 ± 10	69 ± 15	105 ± 9	68 ± 13
Signaling
WT	100	383 ± 41^{^a}	330 ± 24^{^a}	98 ± 9	219 ± 23^{^a}	44 ± 6
S58C	16 ± 2^**	34 ± 9	42 ± 9	24 ± 3	60 ± 12^{^a}	10 ± 2
E61K	14 ± 2^**	4 ± 2	17 ± 3	13 ± 0	81 ± 5^{^a}	12 ± 2
N62S	10 ± 3^**	13 ± 2	28 ± 3^{^b}	14 ± 4	68 ± 4^{^a}	10 ± 2
I69T	5 ± 1^**	42 ± 13^{^b}	164 ± 25^{^a}	18 ± 6	76 ± 14^{^a}	25 ± 8
I125K	7 ± 1^**	6 ± 0	8 ± 0	7 ± 2	8 ± 2	12 ± 1
T162I	6 ± 1^**	16 ± 0	6 ± 1	33 ± 14	102 ± 17^{^a}	6 ± 1
R165Q	6 ± 0^**	97 ± 9^{^a}	127 ± 32^{^a}	56 ± 6^{^a}	249 ± 54^{^a}	36 ± 8^{^b}
R165W	3 ± 1^**	94 ± 21^{^a}	115 ± 16^{^a}	17 ± 1^{^b}	205 ± 11^{^a}	17 ± 1^{^b}
C271Y	4 ± 1^**	4 ± 1	10 ± 1	7 ± 3	32 ± 8^{^a}	9 ± 4
Ratio
WT	1	2.23	2.44	0.68	1.16	0.23
S58C	0.40	0.33	0.39	0.32	0.33	0.04
E61K	0.54	0.11	0.23	0.31	0.73	0.16
N62S	0.56	0.28	0.22	0.38	0.41	0.07
I69T	0.15	0.67	0.96	0.29	0.66	0.26
I125K	0.07	0.03	0.07	0.08	0.04	0.06
T162I	0.29	0.26	0.05	0.45	0.76	0.05
R165Q	0.38	0.47	0.37	0.64	0.90	0.13
R165W	0.19	1.09	1.11	0.15	0.72	0.06
C271Y	0.17	0.15	0.17	0.1	0.3	0.13

↵a Significantly different from untreated condition, P < 0.01.
↵b Significantly different from untreated condition, P < 0.05.
↵** Significantly different from untreated WT hMC4R, P < 0.01.