WY-14643

WY-14643, also known as pirinixic acid, is a selective PPARα agonist. WY-14643 negatively inhibits NF-κB transcriptional activity and decreases the inflammatory response in vitro and in vivo.

Product information

CAS Number: 50892-23-4

Molecular Weight: 323.80

Formula: C14H14ClN3O2S

Synonym:

Pirinixic Acid

Chemical Name: [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio]-acetic acid

Smiles: CC1=C(C=CC=C1C)NC1=CC(Cl)=NC(=N1)SCC(O)=O

InChiKey: SZRPDCCEHVWOJX-UHFFFAOYSA-N

InChi: InChI=1S/C14H14ClN3O2S/c1-8-4-3-5-10(9(8)2)16-12-6-11(15)17-14(18-12)21-7-13(19)20/h3-6H,7H2,1-2H3,(H,19,20)(H,16,17,18)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

WY-14643 is an agonist of PPARα, with EC50s of 0.63 μM, 32 μM for murine PPARα and PPARγ, and 5.0 μM, 60 μM, 35 μM for human PPARα, PPARγ and PPARδ, respectively. WY-14643 (Wy-14643; 0, 10, 100 μM) enhances protein expression of PPAR-α in synovial fibroblasts. WY-14643 (0, 10, 100 μM) shows inhibitroy effects on NO and PGE2 production in LPS-stimulated synovial fibroblasts. WY-14643 also effectively downregulates expression of inflammatory mediators such as VCAM-1, ICAM-1, ET-1, and TF in synovial fibroblasts, blocks LPS-induced NF-kB activation, IkB phosphorylation, and NF-kB nuclear translocation in synovial fibroblasts, but Pirinixic acid shows no effects in PPAR-α silenced cells.

In Vivo:

WY-14643 (Wy-14643; 10 mg/kg, i.v.) decreases hepatic injury and lipid peroxidation (MDA) levels in obese rats. WY-14643 also causes increased SIRT1 activity in Sham and ischemia-reperfusion (IR) group, but shows no effects on SIRT3 protein expression. WY-14643 enhances NAD+, and ATP levels, and prevents endoplasmic reticulum stress (ERS) in rats.

References:

1. Merk D, Zettl M, Steinhilber D, Werz O, Schubert-Zsilavecz M. Pirinixic acids: flexible fatty acid mimetics with various biological activities. Future Med Chem. 2015 Aug;7(12):1597-616. doi: 10.4155/fmc.15.87. Epub 2015 Aug 27. PubMed PMID: 26313377.
2. Hecker M, Behnk A, Morty RE, Sommer N, Vadasz I, Herold S, Seeger W, Mayer K. PPAR-α activation reduced LPS-induced inflammation in alveolar epithelial cells. Exp Lung Res. 2015 Sep;41(7):393-403. doi: 10.3109/01902148.2015.1046200. PubMed PMID: 26151160.
3. Du WW, Liu F, Shan SW, Ma XC, Gupta S, Jin T, Spaner D, Krylov SN, Zhang Y, Ling W, Yang BB. Inhibition of Dexamethasone-induced Fatty Liver Development by Reducing miR-17-5p Levels. Mol Ther. 2015 Jul;23(7):1222-33. doi: 10.1038/mt.2015.64. Epub 2015 Apr 21. PubMed PMID: 25896250.

Products are for research use only. Not for human use.