Orforglipron

Orforglipron is a nonpeptide agonist of the glucagon-like peptide 1 receptor (GLP-1R). It induces cAMP accumulation in HEK293 cells expressing human GLP-1R (EC50 = 3.05 nM) and is selective for GLP-1R over the glucagon receptor (GCGR), gastric inhibitory polypeptide (GIP) receptor, and GLP-2R at 100 nM. Orforglipron (0.1, 1, or 10 mg/kg) prevents increases in blood glucose levels in glucose-injected fasted mice expressing human GLP-1R but not in glucose-injected Glp1r-/- fasted mice. In vivo, orforglipron (5.4 mg/kg) decreases blood glucose and serum insulin levels in glucose-injected cynomolgus monkeys. It reduces mean food intake in cynomolgus monkeys when administered at doses of 0.05 or 0.1 mg/kg per day.Formal Name: 3-[(1S,2S)-1-[2-[[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2,3-dihydro-2-oxo-1H-imidazol-1-yl]-2,4,6,7-tetrahydro-4-methyl-5H-pyrazolo[4,3-c]pyridin-5-yl]carbonyl]-5-[(4S)-tetrahydro-2,2-dimethyl-2H-pyran-4-yl]-1H-indol-1-yl]-2-methylcyclopropyl]-1,2,4-oxadiazol-5(2H)-one. CAS Number: 2212020-52-3. Synonyms: LY3502970, OWL833. Molecular Formula: C48H48F2N10O5. Formula Weight: 883.0. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: Methanol: Soluble. SMILES: O=C(N(CCC1=NN(C(C=C2C)=CC(C)=C2F)C(N(C=CN3C4=CC=C5C(C=NN5C)=C4F)C3=O)=C61)[C@H]6C)C7=CC8=CC([C@@H](CCO9)CC9(C)C)=CC=C8N7[C@]%10(C%11=NOC(N%11)=O)[C@@H](C)C%10. InChi Code: InChI=1S/C48H48F2N10O5/c1-25-18-32(19-26(2)40(25)49)60-42(58-16-15-57(46(58)63)37-11-10-36-33(41(37)50)24-51-55(36)7)39-28(4)56(14-12-34(39)53-60)43(61)38-21-31-20-29(30-13-17-64-47(5,6)23-30)8-9-35(31)59(38)48(22-27(48)3)44-52-45(62)65-54-44/h8-11,15-16,18-21,24,27-28,30H,12-14,17,22-23H2,1-7H3,(H,52,54,62)/t27-,28-,30-,48-/m0/s1. InChi Key: USUWIEBBBWHKNI-KHIFEHGGSA-N.