Orforglipron

Orforglipron is a synthetic nonpeptide molecule characterized as a selective, high-affinity agonist at the human GLP-1 receptor.

Orforglipron is a nonpeptide small molecule, not a peptide. It is documented in this library because it is characterized at the GLP-1 receptor, the same receptor as the peptide analogs semaglutide, liraglutide and exenatide, and because the cited structural work compares nonpeptide and peptide binding at that receptor. The development code LY3502970 appears in the PubChem synonym set and throughout the primary literature; both designations resolve to the same molecular record.

Declared aliases and development codes: LY3502970.

Orforglipron is a nonpeptide agonist of the receptor activated by endogenous GLP-1. Residue substitutions relative to GLP-1 are not applicable, rather than unknown or undetermined: this molecule is not a peptide and has no sequence to align. The related GLP-1(7-36) amide entry is a native receptor comparator only, not a structural parent. Competition binding experiments report orforglipron as a high-affinity ligand of the human GLP-1 receptor with an inhibition constant of approximately 1 nM. Signal transduction assays report low intrinsic activation of downstream effectors and negligible beta-arrestin recruitment. Structural work on the same molecule reports a high-resolution active-state receptor structure in which the nonpeptide agonist occupies a binding pocket in the upper helical bundle that is distinct from the peptide-binding mode, which is the basis for comparing the two ligand classes at a single receptor.