Retatrutide (LY3437943) is a triple agonist of the glucagon receptor, glucose-dependent insulinotropic polypeptide receptor, and glucagon-like peptide-1 receptor (GLP-1R), and inhibits GCGR, GIPR, and GLP-1R.Retatrutide can be used to study obesity.

GCGR:5.79 nM (EC50, human), GCGR:2.32 nM (EC50, mouse), GCGR:73 nM (Ki, mouse), GCGR:5.6 nM (Ki, human), GLP1R:0.775 nM (EC50, human), GLP1R:1.3 nM (Ki, mouse), GLP1R:7.2 nM (Ki, human), GLP1R:0.794 nM (EC50, mouse), GIPR:0.191 nM (EC50, mouse), GIPR:2.8 nM (Ki, mouse), GIPR:0.0643 nM (EC50, human), GIPR:0.057 nM (Ki, human)

Retatrutide (LY3437943) 对人类GCGR、GIPR和GLP-1R展示了活性，其EC50值分别为5.79、0.0643和0.775 nM[1]。对于小鼠GCGR、GIPR和GLP-1R，Retatrutide同样显示出活性，其EC50值分别为2.32、0.191和0.794 nM[1]。就结合亲和力而言，Retatrutide对人类GCGR、GIPR和GLP-1R的Ki值分别为5.6、0.057和7.2 nM[1]。同样地，对于小鼠GCGR、GIPR和GLP-1R，Retatrutide展现出的结合亲和力的Ki值分别为73、2.8和1.3 nM[1]。

在体内，Retatrutide（LY3437943）通过与GCGR相互作用，在单剂量0.47 mg/kg的皮下注射后，通过激活GIP或GLP-1受体在ipGTT（腹腔内葡萄糖耐量测试）中改善葡萄糖耐受性[1]。每3天以10 mL/kg的剂量进行皮下注射，持续21天的周期内，Retatrutide通过激活胰高血糖素受体导致显著的体重减轻和能量消耗增加[1]。