It is mixed PPAR-B agonist antagonist depending on its dosage.[6] It has weak activity on multiple nuclear receptors as well. It is antagonistic at androgen receptors andVDR.[6][7] In silico modelling suggest that it has effects on thyroid hormone receptors.[8]
Multiple derivatives of GW0742 core structure have been developed. One of the compounds has the thiazole ring replaced with an oxazole ring inhibited VDR-meditated transcription with IC50 of 660 nM.[7] Other novel analogues which are more potent than GWO742 with reduced toxicity have been developed as well.[9]
GW0742 has been shown to ameliorate experimentally induced pancreatitis in mice.[10] Additionally, it prevents hypertension in diet induced obese mice,[11] has been investigated as potential antidiabetic drug,[12] and has anti-inflammatory effects.[13][14][11]
^Smith SA, Monteith GR, Robinson JA, Venkata NG, May FJ, Roberts-Thomson SJ (July 2004). "Effect of the peroxisome proliferator-activated receptor beta activator GW0742 in rat cultured cerebellar granule neurons".Journal of Neuroscience Research.77 (2):240–9.doi:10.1002/jnr.20153.PMID15211590.S2CID21295375.
^Haskova Z, Hoang B, Luo G, Morgan LA, Billin AN, Barone FC, et al. (July 2008). "Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine production by the selective PPARbeta/delta ligand GW0742".Inflammation Research.57 (7):314–21.doi:10.1007/s00011-007-7157-4.PMID18622687.S2CID25631088.
^Sznaidman ML, Haffner CD, Maloney PR, Fivush A, Chao E, Goreham D, Sierra ML, LeGrumelec C, Xu HE, Montana VG, Lambert MH, Willson TM, Oliver WR, Sternbach DD (May 2003). "Novel selective small molecule agonists for peroxisome proliferator-activated receptor δ (PPARδ)--synthesis and biological activity".Bioorganic & Medicinal Chemistry Letters.13 (9):1517–21.doi:10.1016/s0960-894x(03)00207-5.PMID12699745.
^Paterniti I, Mazzon E, Riccardi L, Galuppo M, Impellizzeri D, Esposito E, Bramanti P, Cappellani A, Cuzzocrea S (July 2012). "Peroxisome proliferator-activated receptor β/δ agonist GW0742 ameliorates cerulein- and taurocholate-induced acute pancreatitis in mice".Surgery.152 (1):90–106.doi:10.1016/j.surg.2012.02.004.PMID22521259.
^abToral M, Gómez-Guzmán M, Jiménez R, Romero M, Zarzuelo MJ, Utrilla MP, Hermenegildo C, Cogolludo Á, Pérez-Vizcaíno F, Gálvez J, Duarte J (September 2015). "Chronic peroxisome proliferator-activated receptorβ/δ agonist GW0742 prevents hypertension, vascular inflammatory and oxidative status, and endothelial dysfunction in diet-induced obesity".Journal of Hypertension.33 (9):1831–44.doi:10.1097/HJH.0000000000000634.PMID26147382.S2CID38565637.
^Di Paola R, Esposito E, Mazzon E, Paterniti I, Galuppo M, Cuzzocrea S (August 2010). "GW0742, a selective PPAR-beta/delta agonist, contributes to the resolution of inflammation after gut ischemia/reperfusion injury".Journal of Leukocyte Biology.88 (2):291–301.doi:10.1189/jlb.0110053.PMID20430778.S2CID21168990.
^Haskova Z, Hoang B, Luo G, Morgan LA, Billin AN, Barone FC, Shearer BG, Barton ME, Kilgore KS (July 2008). "Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine production by the selective PPARbeta/delta ligand GW0742".Inflammation Research.57 (7):314–21.doi:10.1007/s00011-007-7157-4.PMID18622687.S2CID25631088.
