GSK3787

SKU: orb1225825

Description

GSK3787 is as a selective and irreversible antagonist of PPARδ with pIC50 of 6.6, with no measurable affinity for hPPARα or hPPARγ.

Key Properties

• CAS Number: 188591-46-0
• MW: 392.78
• Purity: >98% (HPLC)
• Formula: C₁₅H₁₂ClF₃N₂O₃S
• SMILES: O=C(NCCS(=O)(C1=NC=C(C(F)(F)F)C=C1)=O)C2=CC=C(Cl)C=C2
• Target: PPAR
• Solubility: DMSO: 79 mg/mL (201.13 mM)

Bioactivity

• 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. 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.
• 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

GSK3787 | GSK-3787 | GSK 3787

Quick Database Links

Gene Symbol

PPAR