Pirinixic acid

Pirinixic acid (Wy-14643) is a potent agonist of PPARα, with EC₅₀s of 0.63 μM, 32 μM for murine PPARα and PPARγ, and 5.0 μM, 60 μM, 35 μM for human PPARα, PPARγ and PPARδ, respectively. IC50 & Target: EC50: 0.63 μM (Murine PPARα), 32 μM (Murine PPARγ), 5.0 μM (Human PPARα), 60 μM (Human PPARγ), 35 μM (Human PPARδ)^[1] In Vitro: Pirinixic acid (Wy-14643) is an agonist of PPARα, with EC₅₀s of 0.63 μM, 32 μM for murine PPARα and PPARγ, and 5.0 μM, 60 μM, 35 μM for human PPARα, PPARγ and PPARδ, respectively^[1]. Pirinixic acid (Wy-14643; 0, 10, 100 μM) enhances protein expression of PPAR-α in synovial fibroblasts. Pirinixic acid (0, 10, 100 μM) shows inhibitroy effects on NO and PGE2 production in LPS-stimulated synovial fibroblasts. Pirinixic acid also effectively downregulates expression of inflammatory mediators such as VCAM-1, ICAM-1, ET-1, and TF in synovial fibroblasts, blocks LPS-induced NF-kB activation, IkB phosphorylation, and NF-kB nuclear translocation in synovial fibroblasts, but Pirinixic acid shows no effects in PPAR-α silenced cells^[2]. In Vivo: Pirinixic acid (Wy-14643; 10 mg/kg, i.v.) decreases hepatic injury and lipid peroxidation (MDA) levels in obese rats. Pirinixic acid also causes increased SIRT1 activity in Sham and ischemia-reperfusion (IR) group, but shows no effects on SIRT3 protein expression. Pirinixic acid enhances NAD⁺, and ATP levels, and prevents endoplasmic reticulum stress (ERS) in rats^[3].