TABLE 3

Overview of efficacy and relative potency of each compound on cell surface rescue

Untreated indicates relative membrane expression reported as a percentage of the value obtained in the same experiment for the hMC4R (WT) in the absence of antagonist. Efficacy refers to relative surface expression level attained after overnight incubation with 10 μM antagonist. Relative potency is the ratio between the mean of the relative surface expression level obtained at 1 and 10 μM. Data shown are the mean ± S.E.M. of at least three independent experiments and are derived from Fig. 3.

ConstructUntreatedEfficacy at 10 μMRelative Potency
MTHPPPPoneMPCIDCPMPNBPMTHPPPPoneMPCIDCPMPNBP
WT100172 ± 7a135 ± 6a144 ± 10a189 ± 34b192 ± 38b0.740.990.750.910.96
S58C40 ± 5*102 ± 4a108 ± 4a74 ± 17184 ± 31b229 ± 20b0.530.450.410.810.73
E61K26 ± 3*37 ± 373 ± 16b42 ± 7111 ± 2b73 ± 9bN.A.0.47N.A.0.640.65
N62S18 ± 8**47 ± 9130 ± 32b37 ± 9165 ± 19b138 ± 23bN.A.0.19N.A.0.520.23
I69T34 ± 1*63 ± 16171 ± 39c63 ± 7115 ± 17b97 ± 8aN.A.0.37N.A.0.860.76
I125K105 ± 8204 ± 9c114 ± 1689 ± 13186 ± 11b217 ± 4c0.930.991.080.820.83
T162I21 ± 2*61 ± 17a132 ± 23c74 ± 10a134 ± 8b113 ± 17b0.380.230.810.820.63
R165Q16 ± 4**208 ± 32c344 ± 31c88 ± 15a278 ± 29c277 ± 34c0.190.250.300.860.56
R165W16 ± 5**86 ± 5a104 ± 10b116 ± 12b283 ± 20c294 ± 16c0.460.370.261.040.41
C271Y24 ± 3*26 ± 0.559 ± 10a69 ± 15a105 ± 9b68 ± 13aN.A.0.440.750.670.96
P299H18 ± 5**20 ± 327 ± 517 ± 420 ± 420 ± 3N.A.N.A.N.A.N.A.N.A.
  • N.A., not applicable (no significant rescue was observed at high concentration).

  • a Significantly different from untreated condition, P < 0.05.

  • b Significantly different from untreated condition, P < 0.01.

  • c Significantly different from untreated condition, P < 0.001.

  • * Significantly different from untreated WT hMC4R, P < 0.05.

  • ** Significantly different from untreated WT hMC4R, P < 0.01.