GW0742

• CAT Number: I003134
• CAS Number: 317318-84-6
• Molecular Formula: C21H17F4NO3S2
• Molecular Weight: 471.5
• Purity: ≥95%
• Target: PPAR
• Solubility: DMSO: ≥ 34 mg/mL
• Storage: 3 years -20C powder
• IC50: 1nM, 1.1μM and 2 μM (EC50, for PPARδ, -α, and -γ)
• InChI: InChI=1S/C21H17F4NO3S2/c1-11-7-14(4-6-17(11)29-9-19(27)28)30-10-18-12(2)26-20(31-18)13-3-5-15(16(22)8-13)21(23,24)25/h3-8H,9-10H2,1-2H3,(H,27,28)
• InChIKey: HWVNEWGKWRGSRK-UHFFFAOYSA-N
• SMILES: CC1=CC(SCC2=C(C)N=C(C3=CC=C(C(F)(F)F)C(F)=C3)S2)=CC=C1OCC(O)=O

GW0742 (GW610742) is a potent and highly selective PPARδ agonist. EC50 values are 1nM, 1.1μM and 2 μM for transactivation of human PPARδ, -α, and -γ receptors respectively.IC50 value: 1nM, 1.1μM and 2 μM (EC50, for PPARδ, -α, and -γ)Target: PPARin vivo: GW0742 is a synthetic high affinity PPAR β/δ agonist, and its possible role in preventing the advance of inflammatory and apoptotic processes induced by bleomycin, that long-term leads to the appearance of pulmonary fibrosis. Our data showed that GW0742-treatment (0.3 mg/Kg, 10 percent DMSO, i.p.) has therapeutic effects on pulmonary damage, decreasing many inflammatory and apoptotic parameters detected by measurement of: 1) cytokine production; 2) leukocyte accumulation, indirectly measured as decrease of myeloperoxidase (MPO) activity; 3) IkBα degradation and NF-kB nuclear translocation; 4) ERK phosphorylation; 5) stress oxidative by NO formation due to iNOS expression; 6) nitrotyrosine and PAR localization; 7) the degree of apoptosis, evaluated by Bax and Bcl-2 balance, FAS ligand expression and TUNEL staining. Taken together, our results clearly show that GW0742 reduces the lung injury and inflammation due to the intratracheal BLEO–instillation in mice.[1]

Reference

1:The Non-Genomic Effects of the PPARβγ agonist GW0742 on STZ treated rat aorta. Perez-Diaz N, Pushkarskya I, Oweisa N, Lionea LA, Mackenzie LS.Curr Mol Pharmacol. 2016 Dec 29. [Epub ahead of print] PMID: 28034288 2:Effect of PPAR-β/δ agonist GW0742 treatment in the acute phase response and blood-brain barrier permeability following brain injury. Chehaibi K, le Maire L, Bradoni S, Escola JC, Blanco-Vaca F, Slimane MN.Transl Res. 2017 Apr;182:27-48. doi: 10.1016/j.trsl.2016.10.004. Epub 2016 Oct 18. PMID: 27818230 3:Pulmonary Administration of GW0742, a High-Affinity Peroxisome Proliferator-Activated Receptor Agonist, Repairs Collapsed Alveoli in an Elastase-Induced Mouse Model of Emphysema. Ozawa C, Horiguchi M, Akita T, Oiso Y, Abe K, Motomura T, Yamashita C.Biol Pharm Bull. 2016;39(5):778-85. doi: 10.1248/bpb.b15-00909. PMID: 27150147 Free Article4:PPARδ agonist GW0742 ameliorates Aβ1-42-induced hippocampal neurotoxicity in mice. An YQ, Zhang CT, Du Y, Zhang M, Tang SS, Hu M, Long Y, Sun HB, Hong H.Metab Brain Dis. 2016 Jun;31(3):663-71. doi: 10.1007/s11011-016-9800-7. Epub 2016 Feb 11. PMID: 26864581 5:Development of PPAR-agonist GW0742 as antidiabetic drug: study in animals. Niu HS, Ku PM, Niu CS, Cheng JT, Lee KS.Drug Des Devel Ther. 2015 Oct 14;9:5625-32. doi: 10.2147/DDDT.S95045. eCollection 2015. PMID: 26508837 Free PMC Article6:The PPARβ/δ Agonist GW0742 Induces Early Neuronal Maturation of Cortical Post-Mitotic Neurons: Role of PPARβ/δ in Neuronal Maturation. Benedetti E, Di Loreto S, D/’Angelo B, Cristiano L, d/’Angelo M, Antonosante A, Fidoamore A, Golini R, Cinque B, Cifone MG, Ippoliti R, Giordano A, Cimini A.J Cell Physiol. 2016 Mar;231(3):597-606. doi: 10.1002/jcp.25103. PMID: 26206209 7:Chronic peroxisome proliferator-activated receptorβ/δ agonist GW0742 prevents hypertension, vascular inflammatory and oxidative status, and endothelial dysfunction in diet-induced obesity. Toral M, Gómez-Guzmán M, Jiménez R, Romero M, Zarzuelo MJ, Utrilla MP, Hermenegildo C, Cogolludo Á, Pérez-Vizcaíno F, Gálvez J, Duarte J.J Hypertens. 2015 Sep;33(9):1831-44. doi: 10.1097/HJH.0000000000000634. PMID: 26147382 8:Modulation of Transcription mediated by the Vitamin D Receptor and the Peroxisome Proliferator-Activated Receptor δ in the presence of GW0742 analogs. Teske K, Nandhikonda P, Bogart JW, Feleke B, Sidhu P, Yuan N, Preston J, Goy R, Arnold LA.J Biomol Res Ther. 2014;3(1). pii: 1000111. PMID: 25485183 Free PMC Article9:The peroxisome proliferator-activated receptor β/δ agonist GW0742 has direct protective effects on right heart hypertrophy. Kojonazarov B, Luitel H, Sydykov A, Dahal BK, Paul-Clark MJ, Bonvini S, Reed A, Schermuly RT, Mitchell JA.Pulm Circ. 2013 Dec;3(4):926-35. doi: 10.1086/674755. Erratum in: Pulm Circ. 2014 Jun;4(2):352. PMID: 25006409 Free PMC Article10:The PPARβ/δ agonist GW0742 modulates signaling pathways associated with cardiac myocyte growth via a non-genomic redox mechanism. Galatou E, Kelly T, Lazou A.Mol Cell Biochem. 2014 Oct;395(1-2):145-54. doi: 10.1007/s11010-014-2120-5. Epub 2014 Jun 18. PMID: 24939361