Description
Cas:188591-46-0
Product Information:
GSK-3787 is a selective and irreversible peroxisome proliferator-activated receptor delta (PPARdelta) antagonist with good pharmacokinetic properties. GSK3787 can antagonize PPARbeta/delta in vivo, thus providing a new strategy to delineate the functional role of a receptor with great potential as a therapeutic target for the treatment and prevention of disease.
Chemical Formula: C15H12ClF3N2O3S
Exact Mass: 392.02093
Molecular Weight: 392.78059
Elemental Analysis: C, 45.87; H, 3.08; Cl, 9.03; F, 14.51; N, 7.13; O, 12.22; S, 8.16
Synonym:
GSK3787
GSK-3787
GSK 3787
Chemical Name: 4-chloro-N-(2-((5-(trifluoromethyl)pyridin-2-yl)sulfonyl)ethyl)benzamide
InChi Key:
JFUIMTGOQCQTPF-UHFFFAOYSA-N
InChi Code: InChI=1S/C15H12ClF3N2O3S/c16-12-4-1-10(2-5-12)14(22)20-7-8-25(23,24)13-6-3-11(9-21-13)15(17,18)19/h1-6,9H,7-8H2,(H,20,22)
Smiles Code:
O=C(NCCS(=O)(C1=NC=C(C(F)(F)F)C=C1)=O)C2=CC=C(Cl)C=C2
Technical Data:
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: soluble in DMSO, not soluble in water.
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
In Vitro:
GSK3787 is identified as a potent and selective hPPARδ ligand (pIC50=6.6) with no measurable affinity for hPPARα or hPPARγ (pIC50 < 5) in our standard in vitro ligand displacement assay. GSK3787 is inactive against hPPARα and hPPARγ in similar functional antagonist assays. GSK3787 fails to activate the receptor in a standard hPPARδ-GAL4 chimera cell-based reporter assay. GSK3787 is a selective PPARδ antagonist with equipotent species activity against the human and mouse receptor.
In Vivo:
GSK3787 has pharmacokinetic properties suitable for use as an in vivo PPARδ antagonist tool compound in mice. GSK3787 is administered intravenously (0.5 mg/kg) and orally (10 mg/kg) to male C57BL/6 mice. Mean clearance (CL) and volume of distribution at steady state (Vss) following iv administration are 39±11 (mL/min)/kg and 1.7±0.4 L/kg, respectively. Following oral administration, good exposure (Cmax=881±166 ng/mL, AUCinf=3343±332 h•ng/mL), half-life (2.7±1.1 h), and bioavailability (F=77±17%) are observed[1]. Oral administration of GSK3787 (10 mg/kg) leads to a serum Cmax of 2.2±0.4 μM in C57BL/6 male mice. Oral administration of GW0742 causes an increase in expression of Angptl4 and Adrp mRNA (known PPARβ/δ target genes) in wild-type mouse colon epithelium, and this effect is not found in Pparβ/δ-null mouse colon epithelium. Coadministration of GSK3787 with GW0742 effectively prevents the ligand-induced expression of both Angptl4 and Adrp mRNA in wild-type mouse colon epithelium, and this effect is not found in Pparβ/δ-null mouse colon epithelium. Oral administration of GSK3787 causes a modest increase in promoter occupancy of PPARβ/δ in the PPRE region of both the Angptl4 and Adrp genes, but coadministration of GSK3787 with GW0742 results in markedly less accumulation of PPARβ/δ in the PPRE region of both the Angptl4 and Adrp genes in wild-type mouse colon epithelium.
References:
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Gu Y, Li X, He T, Jiang Z, Hao P, Tang X. The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptor δ on Rat Corneal Wound Healing after Excimer Laser Keratectomy. PPAR Res. 2014;2014:464935. doi: 10.1155/2014/464935. Epub 2014 Nov 13. PubMed PMID: 25477952; PubMed Central PMCID: PMC4248330.
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Zhou X, Ringseis R, Wen G, Eder K. Carnitine transporter OCTN2 and carnitine uptake in bovine kidney cells is regulated by peroxisome proliferator-activated receptor β/δ. Acta Vet Scand. 2014 Apr 9;56:21. doi: 10.1186/1751-0147-56-21. PubMed PMID: 24716857; PubMed Central PMCID: PMC3998222.
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Luo G, Shi Y, Zhang J, Mu Q, Qin L, Zheng L, Feng Y, Berggren-Söderlund M, Nilsson-Ehle P, Zhang X, Xu N. Palmitic acid suppresses apolipoprotein M gene expression via the pathway of PPARβ/δ in HepG2 cells. Biochem Biophys Res Commun. 2014 Feb 28;445(1):203-7. doi: 10.1016/j.bbrc.2014.01.170. Epub 2014 Feb 4. PubMed PMID: 24508264.
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Chen YC, Chu LY, Yang SF, Chen HL, Yet SF, Wu KK. Prostacyclin and PPARα agonists control vascular smooth muscle cell apoptosis and phenotypic switch through distinct 14-3-3 isoforms. PLoS One. 2013 Jul 3;8(7):e69702. doi: 10.1371/journal.pone.0069702. Print 2013. PubMed PMID: 23844263; PubMed Central PMCID: PMC3701049.
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Hack K, Reilly L, Palmer C, Read KD, Norval S, Kime R, Booth K, Foerster J. Skin-targeted inhibition of PPAR β/δ by selective antagonists to treat PPAR β/δ-mediated psoriasis-like skin disease in vivo. PLoS One. 2012;7(5):e37097. doi: 10.1371/journal.pone.0037097. Epub 2012 May 14. PubMed PMID: 22606335; PubMed Central PMCID: PMC3351437.
Products are for research use only. Not for human use.
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