GW0742

317318-84-6

C21H17F4NO3S2

DMSO : >= 34 mg/mL (72.11 mM)

Cell Cycle/DNA Damage

GW0742 is a potent PPARbeta and PPARdelta agonist, with an IC₅₀ of 1 nM for human PPARdelta in binding assay, and EC₅₀s of 1 nM, 1.1 uM and 2 uM for human PPARdelta, PPARalpha, and PPARgamma, respectively. IC50 & Target: IC50: 1 nM (Human PPARdelta)^[1]
EC50: 1 nM (Human PPARdelta), 1.1 uM (Human PPARalpha), 2 uM (Human PPARgamma)^[1]
PPARbeta^[2] In Vitro: GW0742 is a potent PPARbeta and PPARdelta agonist, with an IC₅₀ of 1 nM for human PPARdelta, and EC₅₀s of 1 nM, 1.1 uM and 2 uM for human PPARdelta, PPARalpha, and PPARgamma respectively^[1]. GW0742 (100 uM) activates human PPARalpha and mouse PPARbeta in MCF-7 cells. GW0742 (100 uM) significantly reduces low-KCl-induced apoptosis of cerebellar granule neurons. GW0742 shows no obvious inherent toxicity on cerebellar granule neuronal cells after treatment of 3-100 uM for 24 h, but induces increased cell death at 100 uM after 48 hr of treatment. Moreover, GW0742 (100 uM) increases c-Jun expression in cerebellar granule neuron cultures observed at 6 hr^[2]. GW0742 (1 uM) induces PPARdelta protein in neonatal rat cardiomyocytes. GW0742 also raises mRNA levels of long-chain acyl-CoA dehydrogenase (LCAD), very long-chain acyl-CoA dehydrogenase (VLCAD), acyl-CoA oxidase 1 (ACOX1), uncoupling protein 3 (UCP3), malonyl-CoA decarboxylase (MCD), and pyruvate dehydrogenase kinase 4 (PDK4) in neonatal rat cardiomyocytes^[4]. In Vivo: GW0742 (0.3 mg/kg, i.p.) reduces intensity masson-trichrome staining, and attenuates the histological signs in bleomycin instillatio (BLEO)-induced lung injury of mice. GW0742 (0.3 mg/kg, i.p.) also causes a reduction of the BLEO-induced loss body weight, and a decrease of myeloperoxidase (MPO) activity. GW0742 shows significant inhibition of TNF-a and IL-1beta in instilled-mice. GW0742 prevents bleomycin-induced IkB-a degradation, reduces the levels of NF-kB p65 in the lung, and decreases iNOS and p-ERK expression in BLEO-induced mice^[3]. GW0742 (5 mg/kg/day, i.v.) increases PPARdelta protein level in the heart of rats. GW0742 also induces the increase in LCAD, VLCAD, and ACOX1 in the heart of rats^[4].