Identification and Characterization of 4-Chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide (GSK3787), a Selective and Irreversible Peroxisome Proliferator-Activated Receptor δ (PPARδ) Antagonist

4-Chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide 3 (GSK3787) was identified as a potent and selective ligand for PPARδ with good pharmacokinetic properties. A detailed binding study using mass spectral analysis confirmed covalent binding to Cys249 within the PPARδ binding pocket. Gene expression studies showed that pyridylsulfone 3 antagonized the transcriptional activity of PPARδ and inhibited basal CPT1a gene transcription. Compound 3 is a PPARδ antagonist with utility as a tool to elucidate PPARδ cell biology and pharmacology.