Description
WY-14643 (50892-23-4) is a selective PPARα agonist (EC50=0.63, 32 and >100 μM for PPARα,γ and δ, respectively).1? Displays anti-inflammatory activity2 and reduces LPS-induced inflammation in alveolar epithelial cells3. Induces “browning” of white adipocytes in combined treatment with retinoic acid.4? Stimulates ADAM10-mediated proteolysis of? amyloid precursor protein in a mouse model.5 Down regulates NFkB transcriptional activity. Review.6
Uses
A highly potent PPARα agonist
Uses
WY-14643 has been used:
- as a positive control for transfection and luciferase assay
- to stimulate bone marrow–derived macrophages (BMDM) for autophagic flux analysis
- to analyze the regulation of fatty acid metabolism-immune nexus (FAMIN) expression in cell culture
Definition
ChEBI: Pirinixic acid is a member of pyrimidines, an organochlorine compound and an aryl sulfide. It is functionally related to an acetic acid.
General Description
WY-14643 prevents lipopolysaccharide (LPS)-induced inflammation in synovial fibroblasts. It protects cortical neurons from pro-inflammatory mediator-induced cell injuries. WY-14643 has inhibitory effects on pro-inflammatory responses in microglia. It improves oxido-nitrosative stress in disease models and reduces the generation of reactive oxygen species (ROS), nitric oxide (NO) and lipid peroxidation end-products in the brain.
Biological Activity
Selective PPAR α agonist (EC 50 values are 0.63, 32 and > 100 μ M at PPAR α , PPAR γ and PPAR δ respectively). Negatively inhibits NF- κ B transcriptional activity and decreases the inflammatory response in vitro and in vivo .
Biochem/physiol Actions
Selective PPARα agonist.
Safety Profile
Moderately toxic by
ingestion. Suspected carcinogen with
experimental carcinogenic and tumorigenic
data. Mutation data reported. When heated
to decomposition it emits very toxic fumes
of Cl-, NOx and SOx
References
1) Forman et al. (1997), Hypolipidemic drugs, polyunsaturated fatty acids and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta; Proc. Natl. Acad. Sci. USA, 94 4312
2) Devchand et al. (1996), The PPARalpha-leukotriene B4 pathway to inflammation control; Nature, 384 39
3) Heckler et al. (2015), PPAR-a activation reduced LPS-induced inflammation in alveolar epithelial cells; Exp. Lung Res., 41 393
4) Wang et al. (2015), WY14643 combined with all-trans retinoic acid acts via p38 MAPK to induce “browning” of white adipocytes in mice; Genet. Mol. Res., 14 6978
5) Corbett et al. (2015), Activation of peroxisome proliferator-activated receptor alpha stimulates ADAM10-mediated proteolysis of APP; Proc. Natl. Acad. Sci. USA, 112 8445
6) Merk et al. (2015), Pirinixic acids: flexible fatty acid mimetics with various biological activities; Future Med. Chem., 7 1597
