Orforglipron

It features 7 chiral centers, with a molecular formula of C₄₈H₄₈F₂N₁₀O₅ and a molecular weight of 882.97 g/mol, presenting as a white to pale yellow solid powder. Slightly soluble in water yet easily soluble in organic solvents like DMSO and DMF, its LogP of 6.2 and pKa of 8.3 enhance oral absorption, enabling an impressive oral bioavailability of 79%—far exceeding the <1% of peptide GLP-1 APIs. This allows for once-daily oral administration without food or water restrictions, significantly boosting patient adherence compared to injectable alternatives or peptide-based oral formulations. The precise control of its 7 chiral centers (chiral purity ≥99.5%) is critical to ensuring consistent efficacy and safety.

Strictly adhering to ICH Q7 standards, its quality is fully controllable: purity ≥99.0%, single impurity ≤0.1%, total impurity ≤0.5%, and genotoxic impurities strictly limited below 0.1ppm via advanced purification processes (crystallization + recrystallization) and HPLC-MS/MS detection. It exhibits excellent stability, retaining efficacy for 3 years at 25°C/60%RH in solid form, eliminating cold chain needs for transportation and storage, and reducing circulation costs. With a mature industrial synthesis route (8-10 key steps), it has a short production cycle (2-3 weeks per batch) and controllable costs, 60-70% lower than peptide GLP-1 APIs. Having completed Phase III clinical trials, it demonstrates significant blood glucose reduction (HbA1c decrease of 1.3-1.6%) and weight loss (up to 12.4kg in 72 weeks), with broad market prospects upon its expected global approval in 2026, serving as a preferred raw material for oral GLP-1 preparations.