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Purity: ≥98%
GSK3787 (GSK-3787; GSK 3787) is a novel, potent, selective and irreversible antagonist of PPARδ (Peroxisome proliferator-activated receptor δ) with important biological activity. It inhibits PPARδ with a pIC50 of 6.6, also exhibits good pharmacokinetic properties.
| ln Vitro |
Our conventional in vitro ligand displacement experiment identifies GSK3787 as a strong and selective hPPARδ ligand (pIC50=6.6) with no detectable affinity for hPPARα or hPPARγ (pIC50 < 5). Comparable functional antagonist experiments reveal that GSK3787 is inactive against both hPPARα and hPPARγ. In a typical reporter assay using hPPARδ-GAL4 chimeric cells, GSK3787 is unable to activate the receptor. GSK3787 is a human and mouse receptor-specific selective PPARδ antagonist with equipotent species activity[1].
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| ln Vivo |
GSK3787 possesses pharmacokinetic characteristics that make it a useful tool chemical for PPARδ antagonist usage in vivo in mice. Male C57BL/6 mice are given GSK3787 intravenously (0.5 mg/kg) and orally (10 mg/kg). After intravenous injection, the mean clearance (CL) and volume of distribution at steady state (Vss) are 39±11 (mL/min)/kg and 1.7±0.4 L/kg, respectively. 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 noted after oral administration[1]. GSK3787 (10 mg/kg) administered orally causes a serum Cmax of 2.2±0.4 μM in male C57BL/6 mice. Oral administration of GW0742 increases the expression of Angptl4 and Adrp mRNA (known as PPARβ/δ target genes) in the colon epithelium of wild-type mice; this effect is not observed 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. ..While coadministration of GSK3787 with GW0742 results in significantly less accumulation of PPARβ/δ in the PPRE region of both the Angptl4 and Adrp genes in wild-type 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[2].
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| References |
[1]. Shearer BG, et al. Identification and characterization of 4-chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide (GSK3787), a selective and irreversible peroxisome proliferator-activated receptor delta (PPARdelta) antagonist. J Med Chem. 20
[2]. Palkar PS, et al. Cellular and pharmacological selectivity of the peroxisome proliferator-activated receptor-beta/delta antagonist GSK3787. Mol Pharmacol. 2010 Sep;78(3):419-30 |
| Molecular Formula |
C15H12CLF3N2O3S
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| Molecular Weight |
392.78
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| CAS # |
188591-46-0
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| Related CAS # |
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| SMILES |
O=C(NCCS(=O)(C1=NC=C(C(F)(F)F)C=C1)=O)C2=CC=C(Cl)C=C2
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| InChi Key |
JFUIMTGOQCQTPF-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
4-chloro-N-(2-((5-(trifluoromethyl)pyridin-2-yl)sulfonyl)ethyl)benzamide
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| Synonyms |
GSK-3787; GSK 3787; GSK3787;
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.36 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.36 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5460 mL | 12.7298 mL | 25.4595 mL | |
| 5 mM | 0.5092 mL | 2.5460 mL | 5.0919 mL | |
| 10 mM | 0.2546 mL | 1.2730 mL | 2.5460 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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