GW7647

Description

Peroxisome proliferator-activated receptor-α (PPARα) is a ligand-activated transcription factor involved in the regulation of lipid homeostasis. Activation of PPARα results in expression of a variety of genes, particularly those involved in fatty acid β-oxidation, binding, and transport. GW 7647 is a potent, selective agonist of human and murine PPARα It activates human PPARα, PPARγ, and PPARδ with EC₅₀ values of 0.006, 1.1 and 6.2 μM, respectively, in a GAL4-PPAR binding assay. Similar EC₅₀ values of 0.001, 1.3, and 2.9 were observed with the murine receptors. GW 7647 lowered triglycerides 93% and 60% in fat-fed hamsters and rats, respectively, at a dose of 3 mg/kg.

Uses

GW7647 has been used as a peroxisome proliferator-activated receptor α (PPAR α) ligand:

• in defatting medium to treat primary human hepatocytes
• to test its effect on the glycolytic function in cardiomyocytes
• to test its effect on infant mouse heart
• in breast cancer MDA-MB-231 cells to activate PPARs

Uses

GW 7647 is a potent PPARα agonist with 200-fold selectivity over PPARγ and PPARδ. It can also be used for regenerative cardiac cell therapies.

Definition

ChEBI: A monocarboxylic acid that is 2-(phenylsulfanyl)isobutyric acid in which the phenyl group is substituted at the para- position by a 3-aza-7-cyclohexylhept-1-yl group in which the nitrogen is acylated by a (cyclohexylamino)carbonyl group.

General Description

A cell-permeable urea-substituted thioisobutyric acid (ureido-TiBA) compound that acts as a potent and selective PPARα agonist (PPARα, γ and δ - EC₅₀ = 6 nM, 1.1 μM and 6.2 μM for human; 1 nM, 1.3 μM and 2.9 μM for murine, respectively). Also displays in vivo lipid-lowering activity in rats.

Biological Activity

Potent and highly selective PPAR α agonist (EC 50 values are 6, 1100 and 6200 nM for human PPAR α , PPAR γ and PPAR δ receptors respectively). Modulates oleate metabolism and mitochondrial enzyme gene expression in mature myotubules in vitro . Has lipid-lowering effects following oral administration in vivo .

Biochem/physiol Actions

GW7647 reduces serum triglyceride levels and enhances hepatic expression of genes associated with β-oxidation. Usage of GW7647 along with metformin in conditions of liver steatosis or injury improves the enzymatic levels of aspartate transaminase (AST) and alanine transaminase (ALT) in serum.

storage

Store at RT

References

[1] PETER J. BROWN. Identification of a subtype selective human PPARα agonist through parallel-array synthesis[J]. Bioorganic & Medicinal Chemistry Letters, 2001, 11 9: Pages 1225-1227. DOI: 10.1016/s0960-894x(01)00188-3
[2] LISA BAUMGARTNER. Lignan Derivatives from Krameria lappacea Roots Inhibit Acute Inflammation in Vivo and Pro-inflammatory Mediators in Vitro[J]. Journal of Natural Products , 2011, 74 8: 1779-1786. DOI: 10.1021/np200343t
[3] STEPAN ALESHIN. Peroxisome proliferator-activated receptor (PPAR)-gamma positively controls and PPARalpha negatively controls cyclooxygenase-2 expression in rat brain astrocytes through a convergence on PPARbeta/delta via mutual control of PPAR expression levels.[J]. Molecular Pharmacology, 2009, 76 2: 414-424. DOI: 10.1124/mol.109.056010