188591-46-0
188591-46-0 structure
- Name: GSK3787
- Chemical Name: 4-chloro-N-[2-[5-(trifluoromethyl)pyridin-2-yl]sulfonylethyl]benzamide
- CAS Number: 188591-46-0
- Molecular Formula: C15H12ClF3N2O3S
- Molecular Weight: 392.781
- Catalog: Biochemical Inhibitor Metabolism PPAR antagonist
- Create Date: 2018-12-20 22:36:44
- Modify Date: 2024-01-03 15:51:18
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GSK3787 is a selective and irreversible peroxisome proliferator-activated receptor δ (PPARδ) antagonist with pIC50 of 6.6.
| Name | 4-chloro-N-[2-[5-(trifluoromethyl)pyridin-2-yl]sulfonylethyl]benzamide |
|---|---|
| Synonyms |
N1-(2-{[5-(trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)-4-chlorobenzamide
QCR-146 Benzamide, 4-chloro-N-[2-[[5-(trifluoromethyl)-2-pyridinyl]sulfonyl]ethyl]- 4-Chloro-N-(2-{[5-(trifluoromethyl)pyridin-2-yl]sulfonyl}ethyl)benzamide 4-Chloro-N-(2-{[5-(trifluoromethyl)-2-pyridinyl]sulfonyl}ethyl)benzamide GSK 3787 4-Chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide 4-chloro-N-(2-{[5-(trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide Benzamide (4-chloro-N-[2-[[5-(trifluoromethyl)-2-pyridinyl]sulfonyl]ethyl] GSK-3787 GSK3787 |
| Description | GSK3787 is a selective and irreversible peroxisome proliferator-activated receptor δ (PPARδ) antagonist with pIC50 of 6.6. |
|---|---|
| Related Catalog | |
| Target |
PPARδ:6.6 nM (pIC50) |
| 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[1]. |
| 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[2]. |
| Animal Admin | Mice[2] For RNA and DNA analysis, male wild-type and Pparβ/δ-null mice are administered vehicle (corn oil), GW0742 (10 mg/kg), GSK3787 (10 mg/kg), or GW0742 and GSK3787 by oral gavage 3 h before euthanasia. After euthanasia, colons are carefully dissected. To isolate colon epithelium, colons are flushed with phosphate-buffered saline, and epithelial cells are scraped from mucosa using a razor blade. The isolated tissues are used for RNA isolation. For glucose-tolerance tests, male wild-type and Pparβ/δ-null mice are administered vehicle (corn oil), GW0742 (10 mg/kg), GSK3787 (10 mg/kg), or Rosiglitazone (20 mg/kg) by oral gavage once a day for 2 weeks. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Boiling Point | 585.1±50.0 °C at 760 mmHg |
| Molecular Formula | C15H12ClF3N2O3S |
| Molecular Weight | 392.781 |
| Flash Point | 307.7±30.1 °C |
| Exact Mass | 392.020935 |
| PSA | 84.51000 |
| LogP | 2.74 |
| Appearance | white to off-white |
| Vapour Pressure | 0.0±1.6 mmHg at 25°C |
| Index of Refraction | 1.544 |
| Storage condition | Store at +4°C |
| Water Solubility | DMSO: ≥10mg/mL |