Chiglitazar is a PPAR α/γ/δ agonist and insulin sensitizer used in the treatment of type 2 diabetes mellitus to lower blood glucose, regulate blood lipids, and have anti-inflammatory and anti-fibrotic effects.

PPARα:1.2 μM (EC50), PPARγ:0.08 μM (EC50)

The in vitro activity of chiglitazar was evaluated in U-2OS human osteosarcoma cells using luciferase reporter assays. Cells were co-transfected with expression plasmids for PPARα or PPARγ and corresponding reporter constructs, then treated with chiglitazar for 24 hours. Chiglitazar effectively activated both PPARα and PPARγ (EC₅₀ = 1.2 μM and 0.08 μM, respectively), showing stronger PPARα activation than rosiglitazone and pioglitazone, and moderate PPARγ activity compared to rosiglitazone [1].

The in vivo activity of chiglitazar was tested in monosodium glutamate (MSG)-induced obese insulin-resistant rats. Six-month-old MSG rats were divided into groups (n = 10 per group) and treated by oral gavage with chiglitazar (5, 10, or 20 mg/kg/day) or rosiglitazone (5 mg/kg/day) for 40 days. Glucose tolerance (IPGTT), insulin tolerance (ITT), euglycemic-hyperinsulinemic clamp, and alanine-induced gluconeogenesis tests were performed. Chiglitazar improved glucose tolerance, increased insulin sensitivity (higher GIR), suppressed hepatic gluconeogenesis, reduced liver glycogen content, improved plasma lipid profiles (TG, TCHO, NEFA, LDL-C), and decreased hepatic and muscular lipid accumulation. Chiglitazar also upregulated hepatic expression of PPARα target genes (ACO, CPT1, CYP4A10), suggesting enhanced fatty acid oxidation [1].