188591-46-0 Usage
Description
4-Chloro-N-[2-[[5-(trifluoromethyl)-2-pyridinyl]sulfonyl]ethyl]benzamide, also known as GSK3787, is a selective and irreversible antagonist of the peroxisome proliferator-activated receptor δ (PPARδ) with a pIC50 value of 6.6. It covalently binds to Cys 249 in the PPARδ binding site, making it a potent inhibitor of this receptor. 4-Chloro-N-[2-[[5-(trifluoromethyl)-2-pyridinyl]sulfonyl]ethyl]benzamide plays a significant role in lipid homeostasis and glucose disposal by regulating genes involved in fatty acid oxidation, reverse cholesterol transport, and carbon substrate utilization in skeletal muscle. It has also been implicated in the progression of certain cancers.
Uses
Used in Anticancer Applications:
4-Chloro-N-[2-[[5-(trifluoromethyl)-2-pyridinyl]sulfonyl]ethyl]benzamide is used as an antagonist for PPARδ in the context of cancer progression. It inhibits the expression of PPARβ/δ-regulated target genes, such as pyruvate dehydrogenase kinase 4 and carnitine palmitoyl transferase 1a, which are important for energy homeostasis in human skeletal muscle cells. Additionally, GSK3787 (at 1 μM) antagonizes agonist-induced expression of angiopoietin-like protein 4 in various cancer cell lines, including mouse fibroblasts, mouse keratinocytes, and human MCF-7, Huh7, and HepG2.
Used in Embryonic Development Research:
In the field of bovine embryonic development, 4-Chloro-N-[2-[[5-(trifluoromethyl)-2-pyridinyl]sulfonyl]ethyl]benzamide is used as a PPARδ-specific inhibitor during the pre-implantation period to study the role of PPARδ in this process.
Used in In Vitro Maturation (IVM) Media:
4-Chloro-N-[2-[[5-(trifluoromethyl)-2-pyridinyl]sulfonyl]ethyl]benzamide is used as a PPARδ inhibitor in IVM media to study the effects of PPARδ inhibition on the maturation of oocytes and subsequent embryonic development.
Used in Pharmaceutical Research:
In the pharmaceutical industry, 4-Chloro-N-[2-[[5-(trifluoromethyl)-2-pyridinyl]sulfonyl]ethyl]benzamide is used as a research compound for the development of new drugs targeting PPARδ, which may have potential applications in treating various diseases related to lipid metabolism, glucose homeostasis, and cancer progression.
Biochem/physiol Actions
GSK3787 is an orally available selective irreversible Peroxisome Proliferator-Activated Receptor δ (PPARδ) antagonist (pIC50=6.6) with no measurable affinity for hPPARR or hPPARγ (pIC50<5). It acts by covalently modifying Cys249 within the ligand binding pocket, and has been shown to antagonize the induction of PPARδ-regulated target genes in skeletal muscle cells.
References
Shearer et al., (2010)? 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.?53? 1857
Palkar?et al?(2010) Cellular and pharmacological selectivity of the peroxisome proliferator-activated receptor-β/δ antagonist GSK3787; ?Mol.Pharmacol.?78? 419
Check Digit Verification of cas no
The CAS Registry Mumber 188591-46-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,8,8,5,9 and 1 respectively; the second part has 2 digits, 4 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 188591-46:
(8*1)+(7*8)+(6*8)+(5*5)+(4*9)+(3*1)+(2*4)+(1*6)=190
190 % 10 = 0
So 188591-46-0 is a valid CAS Registry Number.
188591-46-0Relevant articles and documents
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
Shearer, Barry G.,Wiethe, Robert W.,Ashe, Adam,Billin, Andrew N.,Way, James M.,Stanley, Thomas B.,Wagner, Craig D.,Xu, Robert X.,Leesnitzer, Lisa M.,Merrihew, Raymond V.,Shearer, Todd W.,Jeune, Michael R.,Ulrich, John C.,Wilison, Timothy M.
experimental part, p. 1857 - 1861 (2010/08/22)
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 CPT1 a gene transcription. Compound 3 is a PPARδ antagonist with utility as a tool to elucidate PPARδ cell biology and pharmacology.
