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.

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Shearer BG, Wiethe RW, Ashe A, Billin AN, Way JM, Stanley TB, Wagner CD, Xu RX, Leesnitzer LM, Merrihew RV, Shearer TW, Jeune MR, Ulrich JC, Willson TM

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. 2010 Feb 25;53(4):1857-61. doi: 10.1021/jm900464j.

PubMed ID

20128594 [ View in PubMed

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Abstract

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

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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Cardarine	Peroxisome proliferator-activated receptor delta	IC 50 (nM)	125.89	N/A	N/A	Details