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Gw0742

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GW0742 is a synthetic and potent agonist for the peroxisome proliferator-activated receptor delta (PPARδ). It acts as a selective activator of PPARδ. The product is intended for laboratory research use.

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Lab products found in correlation

Wy14643, by Merck Group (3 mentions) Le135, by Bio-Techne (2 mentions) Gw7647, by Bio-Techne (2 mentions) L165041, by Bio-Techne (2 mentions) Hepg2 cell, by American Type Culture Collection (2 mentions) Gsk0660, by Bio-Techne (2 mentions) Gsk3787, by Abcam (2 mentions) Mircury lna mirna power inhibitor control, by Qiagen (2 mentions) Txnip crispr activation plasmid, by Santa Cruz Biotechnology (2 mentions) Control crispr activation plasmid, by Santa Cruz Biotechnology (2 mentions) Mircury lna mirna power inhibitor, by Qiagen (2 mentions) Puromycin, by Beyotime (1 mentions) T0901317, by Merck Group (1 mentions) Mifepristone, by Merck Group (1 mentions) Hx531, by Merck Group (1 mentions) Gsk3787, by Bio-Techne (1 mentions) Cd437, by Merck Group (1 mentions) Er50891, by Bio-Techne (1 mentions) Sr9011, by Merck Group (1 mentions) Am580, by Bio-Techne (1 mentions)

17 protocols using gw0742

1

Fatty Acid and PPAR Agonist Treatment Protocol

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OA (Sigma-Aldrich, St. Louis, MO) and PA (Nu-Chek Prep, Elysian, MN) were dissolved in ethanol to a stock concentration of 100 or 200 mM. This was then diluted into media to a final concentration of 100 or 200 uM OA or PA, as used in other cell culture studies (de Vries et al. 1997 (link), Ulloth et al. 2003 (link)). The agonist, GW 0742 (Tocris, Minneapolis, MN), was dissolved in ethanol to make a 10 mM stock solution and was diluted into media to a final concentration of 1 μM, with the EC50 for GW 0742 in activating PPARδ activity in cell culture found to be 1 nM. Higher concentrations were not used, as those higher than 1 μM are found to start activating PPARα and PPARγ (Sznaidman et al. 2003 (link)), and those higher than 10 μM can activate other receptors, such as the vitamin D receptor (Nandhikonda et al. 2013 (link)). To ensure no effect from ethanol, neuronal treatment with diluted ethanol to final working concentrations (1000× or 2000× dilution) alone did not affect the gene expression of PPARs or ENK in hypothalamic or forebrain neurons. Neurons were treated for 24 hours with the agonist and fatty acids.
Poon K., Alam M., Karatayev O., Barson J.R, & Leibowitz S.F. (2015). Regulation of the orexigenic neuropeptide, enkephalin, by PPARδ and fatty acids in neurons of the hypothalamus and forebrain. Journal of neurochemistry, 135(5), 918-931.
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2

Diverse Pharmacological Modulators of Nuclear Receptors

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AM580 (Tocris, #0760, Germany), ER50891 (Tocris, #3823, Germany), CD2314 (Tocris, #3824, Germany), LE135 (Tocris, #2021, Germany), CD437 (Sigma, #C5865, USA), MM11253 (Tocris, #3822, Germany), ATRA (Sigma, #R2625, USA), BMS493 (Sigma, #B6688, USA), GW7647 (Tocris, #1677, Germany), GW6471 (Tocris, #4618, Germany), GW0742 (Tocris, #2229, Germany), GSK3787 (Tocris, #3961, Germany), Troglitazone (Sigma, #T2573, USA), T0070907 (Sigma, #T8703, USA), T0901317 (Sigma, #T2320, USA), SR9238 (Tocris, #5854, Germany), GC1 (Tocris, #4554, Germany), Calcifediol (Tocris, #4036, Germany), SR9011 (Sigma, #SML2067, USA), SR8278 (Tocris, #4463, Germany), CD3254 (Tocris, #3302, Germany), HX531 (Sigma, #SML2170, USA), Testosterone (Aladdin, #T102169, China), Nilutamide (Sigma, #N8534, USA), XCT790 (Sigma, #X4753, USA), Dexamethasone (Sigma, #D4902, USA), Mifepristone (Sigma, #M8046, USA), Corticosterone (Aladdin, #C104537, China), Eplerenone (Sigma, #E6657, USA), Doxorubicin (Solarbio, #D8740, China), Blasticidin (Beyotime, #ST018, China), Puromycin (Beyotime, # ST551, China).
Yuan B., Shi K., Zha J., Cai Y., Gu Y., Huang K., Yue W., Zhai Q., Ding N., Ren W., He W., Xu Y, & Wang T. (2023). Nuclear receptor modulators inhibit osteosarcoma cell proliferation and tumour growth by regulating the mTOR signaling pathway. Cell Death & Disease, 14(1), 51.
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3

Isolation and Characterization of Porcine Auricular Cartilage Cells

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Auricular-derived primary cartilage cells were isolated from external ears of a 4-month-old Duroc × (Landrace × Large White) hybrid (hereafter DLL) pig homozygous for the wild-type allele at PPARD G32E using enzymatic digestion as previously described 9 (link). Cells were cultured at 37 °C in a humid atmosphere of 5% CO2 in DMEM-F12 (Gibco) medium freshly supplemented with 20% fetal bovine serum (Gibco) and antibiotics (Gibco). When the confluence reached 70%, the third-generation primary cells were incubated with 0.1 μM GW0742 while mediums were replaced with DMEM-F12 plus 10% charcoal-stripped serum (Hyclone). After incubated for 24 h, cells were collected for subsequent flow cytometry, RNA sequencing and chromatin immunoprecipitation (ChIP) sequencing analyses. The quantity and quality of isolated RNA and ChIPed DNA samples were analyzed using a Qubit Fluorometer (Thermo Fisher) and a 2100 Bioanalyzer (Agilent). Pig PK-15 cells were cultured in DMEM (high glucose, Gibco) medium supplemented with 10% fetal bovine serum (Gibco) and antibiotic solution. When cells were incubated with the PPARD agonist GW0742 (Tocris), culture mediums were replaced with DMEM plus 5% charcoal-stripped serum (Hyclone).
Zhang Z., Duan Y., Wu Z., Zhang H., Ren J, & Huang L. (2017). PPARD is an Inhibitor of Cartilage Growth in External Ears. International Journal of Biological Sciences, 13(5), 669-681.
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4

Comparative Analysis of Hepatic Cell Lines

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Human hepatoma HepG2 cells and mouse hepatoma AML12 cells were obtained from ATCC. HEK293A cell line was obtained from Invitrogen. Hamster primary hepatocytes were isolated from male golden Syrian hamsters in our laboratory. Human primary hepatocytes were obtained from Invitrogen. Mouse primary hepatocytes were isolated from male C57BL/6 J mice at San Francisco General Hospital Liver Center. L165041 and GW0742 were purchased from TOCRIS Biosciences (Bristol, UK). Cholesterol, 25-hydroxylcholesterl and WY-14643 were purchased from Sigma, and 6α-ethyl-chenodeoxycholic acid (6ECDCA) and 24(S)-hydroxylcholesterol (24-OHC) were purchased from Abcam (Cambridge, MA).
Kan C.F., Singh A.B., Dong B., Shende V.R, & Liu J. (2015). PPARδ activation induces hepatic long-chain acyl-CoA synthetase 4 expression in vivo and in vitro. Biochimica et biophysica acta, 1851(5), 577-587.
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5

Synthesis and Characterization of LG190178

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1,25-(OH)2D3 (calcitriol) was purchased from Endotherm. GW0742 was purchased from Tocris. LG190178 was synthesized using a published procedure.15 (link)
Teske K., Nandhikonda P., Bogart J.W., Feleke B., Sidhu P., Yuan N., Preston J., Goy R, & Arnold L.A. (2014). Modulation of Transcription mediated by the Vitamin D Receptor and the Peroxisome Proliferator-Activated Receptor δ in the presence of GW0742 analogs. Journal of biomolecular research & therapeutics, 3(1), 1000111.
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6

PPARβ/δ agonist treatment in mice

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CON mice were subjected to an intra-peritoneal injection of either 0.9% NaCl (control) or 1 mg/kg of body weight of the PPARβ/δ agonist GW0742 (Tocris #2229, Bristol, UK), as previously described [15 (link)]. Muscles were collected 8 h following drug administration.
Pérez-Schindler J., Svensson K., Vargas-Fernández E., Santos G., Wahli W, & Handschin C. (2014). The coactivator PGC-1α regulates mouse skeletal muscle oxidative metabolism independently of the nuclear receptor PPARβ/δ in sedentary mice fed a regular chow diet. Diabetologia, 57(11), 2405-2412.
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7

PPARβ/δ Modulation in Retinal Cells

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The PPARβ/δ inhibitor GSK0660 and the PPARβ/δ agonist GW0742 were purchased from Tocris (Minneapolis, MN, USA). Palmitic acid and fatty acid-free BSA was purchased from Sigma (St. Louis, MO, USA). Human retinal microvascular endothelial cells (HRMEC) and attachment factor were purchased from Cell Systems (Kirkland, WA, USA). Peripheral blood mononuclear cells were purchased from Sanguine Biosciences (Valencia, CA, USA). TNFα, CCL8, and CXCL10 were purchased from R&D Systems (Minneapolis, MN, USA).
Capozzi M.E., Savage S.R., McCollum G.W., Hammer S.S., Ramos C.J., Yang R., Bretz C.A, & Penn J.S. (2019). The Peroxisome Proliferator-Activated Receptor-β/δ antagonist GSK0660 mitigates Retinal Cell Inflammation and Leukostasis. Experimental eye research, 190, 107885.
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8

Bile Acid Signaling Regulation

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CDCA, CA, deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), glycine or taurine conjugated bile acids, dimethyl sulfoxide (DMSO), DNA oligonucleotides, fetal bovine serum (FBS), charcoal-stripped FBS, pioglitazone (PGZN) and insulin were purchased from Sigma-Aldrich (St. Louis, MO, USA). Luciferase assay kits were from Promega (Madison, WI, USA). Restriction enzymes were from New England BioLabs (Ipswich, MA, USA). Activated charcoal was from Fisher Scientific (Pittsburgh, PA, USA). GW4064, GW7647, GW3965 and GW0742 were purchased from Tocris Bioscience (Minneapolis, MN, USA). Recombinant human AKR1D1 protein was purchased from Novus Biologics (Littleton, CO, USA).
Valanejad L., Ghareeb M., Shiffka S., Nadolny C., Chen Y., Guo L., Verma R., You S., Akhlaghi F, & Deng R. (2017). Dysregulation of Δ4-3-oxosteroid 5β-reductase in Diabetic Patients: Implications and Mechanisms. Molecular and cellular endocrinology, 470, 127-141.
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9

Hepatocyte Isolation and Cell Culture

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Human hepatoma HepG2 cells were obtained from ATCC. L165041 and GW0742 were purchased from TOCRIS Biosciences (Bristol, UK). Actinomycin D and anti-β-actin were purchased from Sigma. Anti-LDLR antibody was obtained from BioVision (Mountain View, CA). Mouse primary hepatocytes were isolated from male C57BL/6J mice at San Francisco General Hospital Liver Center.
Shende V.R., Singh A.B, & Liu J. (2015). A Novel Peroxisome Proliferator Response Element Modulates Hepatic Low Density Lipoprotein Receptor Gene Transcription in Response to PPARδ Activation. The Biochemical journal, 472(3), 275-286.
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10

Agonist and Antagonist Drug Treatments

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According to our previous method,16 (link) the stock solutions of agonist GW0742 (Tocris Bioscience, Bristol, UK) or antagonist GSK0660 (Tocris Bioscience) were prepared in dimethyl sulfoxide. A fresh solution diluted with 9% normal saline to the indicated dose was used to treat the animals. To rule out the pharmacokinetic factors, GW0742 was intravenously injected at the indicated dose into animals under anesthesia. Additionally, GSK0660 was similarly injected 30 minutes before the injection of GW0742. The changes were then used to compare with the control, which was treated with the same volume of vehicle.
Niu H.S., Ku P.M., Niu C.S., Cheng J.T, & Lee K.S. (2015). Development of PPAR-agonist GW0742 as antidiabetic drug: study in animals. Drug Design, Development and Therapy, 9, 5625-5632.
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