Rosiglitazone

Rosiglitazone is an agonist of peroxisome proliferator-activated receptor γ (PPARγ).¹ It activates PPARγ1 and PPARγ2 in reporter assays (EC₅₀s = 30 and 100 nM, respectively). Rosiglitazone selectively activates chimeras containing the ligand-binding domains (LBDs) of PPARγ over PPARα and PPARδ in a cell-based reporter assay at 10 mM. It induces differentiation of C3H10T1/2 stem cells into adipocytes when used at a concentration of 1 µM. Rosiglitazone is also an inhibitor of long-chain acyl-CoA synthetase 4 (ACSL4; IC₅₀ = 0.5 µM).^2,3 It inhibits RSL3-induced ferroptosis in Gpx4 Cre-lox-expressing mouse embryonic fibroblasts (Pfa1) cells and Pparg knockout (KO) cells and increases survival in a Gpx4 KO mouse model of ferroptosis when used at a concentration of 0.0125 mg/ml in the drinking water. It decreases hemoglobin A1c (HbA1c) and fasting blood glucose levels in a rat model of type 2 diabetes induced by streptozotocin (STZ; Item No. 13104) and a high-carbohydrate and high-fat diet when administered at a dose of 4 mg/kg.⁴ Formulations containing rosiglitazone have been used to improve glycemic control in the treatment of type 2 diabetes.

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