Seladelpar CAS# 851528-79-5 司拉德帕

Seladelpar is a highly selective agonist of the peroxisome proliferator-activated receptor delta (PPARδ) (human PPARδ EC₅₀ ≈ 2 nM; >750-fold and >2,500-fold selectivity vs PPARα/γ) in cell assays. In primary mouse hepatocytes treated with 3-30 µM seladelpar for 48 h, the drug significantly reduced hepatic Cyp7a1 (cholesterol-7-α-hydroxylase) mRNA and protein expression, and in vivo in wild-type C57BL/6 mice at 10 mg/kg gavage for 6 h it lowered plasma 7α-hydroxy-4-cholesten-3-one (C4) levels and repressed Cyp7a1 in liver (via induction of Fgf21 → JNK signalling). In disease models, in obese diabetic “foz/foz” mice fed an atherogenic diet, 10 mg/kg seladelpar for 8 weeks normalized hyperglycemia, hyperinsulinemia, reduced ALT by ~50%, abolished hepatocyte ballooning/apoptosis, reduced steatosis/inflammation and improved liver fibrosis (NAFLD activity score dropped from ~6.9 to ~3.1) despite minimal weight loss.