Construct | Untreated | Efficacy at 10 μM | Relative Potency | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|

MTHP | PPPone | MPCI | DCPMP | NBP | MTHP | PPPone | MPCI | DCPMP | NBP | ||

WT | 100 | 172 ± 7^{a} | 135 ± 6^{a} | 144 ± 10^{a} | 189 ± 34^{b} | 192 ± 38^{b} | 0.74 | 0.99 | 0.75 | 0.91 | 0.96 |

S58C | 40 ± 5^{*} | 102 ± 4^{a} | 108 ± 4^{a} | 74 ± 17 | 184 ± 31^{b} | 229 ± 20^{b} | 0.53 | 0.45 | 0.41 | 0.81 | 0.73 |

E61K | 26 ± 3^{*} | 37 ± 3 | 73 ± 16^{b} | 42 ± 7 | 111 ± 2^{b} | 73 ± 9^{b} | N.A. | 0.47 | N.A. | 0.64 | 0.65 |

N62S | 18 ± 8^{**} | 47 ± 9 | 130 ± 32^{b} | 37 ± 9 | 165 ± 19^{b} | 138 ± 23^{b} | N.A. | 0.19 | N.A. | 0.52 | 0.23 |

I69T | 34 ± 1^{*} | 63 ± 16 | 171 ± 39^{c} | 63 ± 7 | 115 ± 17^{b} | 97 ± 8^{a} | N.A. | 0.37 | N.A. | 0.86 | 0.76 |

I125K | 105 ± 8 | 204 ± 9^{c} | 114 ± 16 | 89 ± 13 | 186 ± 11^{b} | 217 ± 4^{c} | 0.93 | 0.99 | 1.08 | 0.82 | 0.83 |

T162I | 21 ± 2^{*} | 61 ± 17^{a} | 132 ± 23^{c} | 74 ± 10^{a} | 134 ± 8^{b} | 113 ± 17^{b} | 0.38 | 0.23 | 0.81 | 0.82 | 0.63 |

R165Q | 16 ± 4^{**} | 208 ± 32^{c} | 344 ± 31^{c} | 88 ± 15^{a} | 278 ± 29^{c} | 277 ± 34^{c} | 0.19 | 0.25 | 0.30 | 0.86 | 0.56 |

R165W | 16 ± 5^{**} | 86 ± 5^{a} | 104 ± 10^{b} | 116 ± 12^{b} | 283 ± 20^{c} | 294 ± 16^{c} | 0.46 | 0.37 | 0.26 | 1.04 | 0.41 |

C271Y | 24 ± 3^{*} | 26 ± 0.5 | 59 ± 10^{a} | 69 ± 15^{a} | 105 ± 9^{b} | 68 ± 13^{a} | N.A. | 0.44 | 0.75 | 0.67 | 0.96 |

P299H | 18 ± 5^{**} | 20 ± 3 | 27 ± 5 | 17 ± 4 | 20 ± 4 | 20 ± 3 | N.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.