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

Autor:	Adam Ashe, Thomas B. Stanley, Todd W Shearer, Craig D. Wagner, John C. Ulrich, Lisa M. Leesnitzer, Barry G. Shearer, Raymond V. Merrihew, Robert W. Wiethe, James M. Way, Robert X. Xu, Andrew N. Billin, Timothy M. Willson, Michael R. Jeune
Rok vydání:	2010
Předmět:	Male Transcription Genetic Stereochemistry Muscle Fibers Skeletal Peroxisome proliferator-activated receptor Antineoplastic Agents Protein Serine-Threonine Kinases Ligands Mass Spectrometry Sulfone Mice Structure-Activity Relationship chemistry.chemical_compound Genes Reporter Cell Line Tumor Drug Discovery Animals Humans Structure–activity relationship Tissue Distribution Cysteine PPAR delta Sulfones Binding site Benzamide chemistry.chemical_classification Sulfonyl Binding Sites Carnitine O-Palmitoyltransferase Ligand Antagonist Pyruvate Dehydrogenase Acetyl-Transferring Kinase Mice Inbred C57BL chemistry Benzamides Molecular Medicine Drug Screening Assays Antitumor
Zdroj:	Journal of Medicinal Chemistry. 53:1857-1861
ISSN:	1520-4804 0022-2623
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8984378fd8ba14814739549a07608292 https://doi.org/10.1021/jm900464j Zobrazit plný text záznamu