CG-0416

CG-0416 is a novel, orally bioavailable, liver-targeted prodrug of a thyroid hormone receptor beta (THR-β) agonist developed by Shanghai CureGene Pharmaceutical. It is designed for the treatment of metabolic diseases, specifically nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated steatohepatitis (MASH), and obesity-related complications. The drug achieves tissue-selective activation in the liver, resulting in intrahepatic concentrations of its active metabolite that are approximately 20-fold higher than those in peripheral tissues. This selectivity minimizes systemic THR-β activation and improves long-term safety compared to existing therapies. In preclinical models, particularly diet-induced obesity mice, CG-0416 demonstrated superior fat mass reduction and muscle preservation when combined with low-dose semaglutide versus semaglutide alone or other THR-beta agonists like resmetirom or VK2809. Mechanistically, it enhances GLP‑1-mediated hepatic lipid oxidation while activating the IGF‑1/Akt/FOXO3a axis to suppress muscle catabolism. With an oral bioavailability of about 92%, it offers potential as part of the first oral combination regimen with GLP‑1 agonists for metabolic disease management[2][1][3].

Other names

CG-0416CG0416CG 0416