Chemistry:GW0742
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Short description: PPAR β/δ receptor Agonist compound
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| Formula | C21H17F4NO3S2 |
| Molar mass | 471.48 g·mol−1 |
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GW0742 (also known as GW610742 and Fitorine) is a PPARδ/β agonist[2][3][4] that has been investigated for drug use by GlaxoSmithKline.[5]
Pharmacology
Pharmacodynamics
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 and VDR.[6][7] In silico modelling suggest that it has effects on thyroid hormone receptors.[8]
Chemistry
Derivatives
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]
Research
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]
See also
References
- ↑ "Cayman Chemical GW0742". https://www.caymanchem.com/app/template/Product.vm/catalog/10006798.
- ↑ "Effect of the peroxisome proliferator-activated receptor beta activator GW0742 in rat cultured cerebellar granule neurons". Journal of Neuroscience Research 77 (2): 240–9. July 2004. doi:10.1002/jnr.20153. PMID 15211590.
- ↑ "Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine production by the selective PPARbeta/delta ligand GW0742". Inflammation Research 57 (7): 314–21. July 2008. doi:10.1007/s00011-007-7157-4. PMID 18622687.
- ↑ "Novel selective small molecule agonists for peroxisome proliferator-activated receptor δ (PPARδ)--synthesis and biological activity". Bioorganic & Medicinal Chemistry Letters 13 (9): 1517–21. May 2003. doi:10.1016/s0960-894x(03)00207-5. PMID 12699745.
- ↑ "Peroxisome proliferator-activated receptor beta stimulation induces rapid cardiac growth and angiogenesis via direct activation of calcineurin". Cardiovascular Research 83 (1): 61–71. July 2009. doi:10.1093/cvr/cvp106. PMID 19351742. https://zenodo.org/record/907733.
- ↑ 6.0 6.1 "Peroxisome proliferation-activated receptor δ agonist GW0742 interacts weakly with multiple nuclear receptors, including the vitamin D receptor". Biochemistry 52 (24): 4193–203. June 2013. doi:10.1021/bi400321p. PMID 23713684.
- ↑ 7.0 7.1 "Novel VDR antagonists based on the GW0742 scaffold". Bioorganic & Medicinal Chemistry Letters 28 (3): 351–354. February 2018. doi:10.1016/j.bmcl.2017.12.041. PMID 29287957.
- ↑ "In silico modelling of prostacyclin and other lipid mediators to nuclear receptors reveal novel thyroid hormone receptor antagonist properties". Prostaglandins & Other Lipid Mediators 122: 18–27. January 2016. doi:10.1016/j.prostaglandins.2015.12.002. PMID 26686607.
- ↑ "Parallel Chemistry Approach to Identify Novel Nuclear Receptor Ligands Based on the GW0742 Scaffold". ACS Combinatorial Science 19 (10): 646–656. October 2017. doi:10.1021/acscombsci.7b00066. PMID 28825467.
- ↑ "Peroxisome proliferator-activated receptor β/δ agonist GW0742 ameliorates cerulein- and taurocholate-induced acute pancreatitis in mice". Surgery 152 (1): 90–106. July 2012. doi:10.1016/j.surg.2012.02.004. PMID 22521259.
- ↑ 11.0 11.1 "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. September 2015. doi:10.1097/HJH.0000000000000634. PMID 26147382.
- ↑ "Development of PPAR-agonist GW0742 as antidiabetic drug: study in animals". Drug Design, Development and Therapy 9: 5625–32. 2015. doi:10.2147/DDDT.S95045. PMID 26508837.
- ↑ "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. August 2010. doi:10.1189/jlb.0110053. PMID 20430778.
- ↑ "Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine production by the selective PPARbeta/delta ligand GW0742". Inflammation Research 57 (7): 314–21. July 2008. doi:10.1007/s00011-007-7157-4. PMID 18622687.
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