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    WY-14643 (Pirinixic Acid)
    WY-14643 (Pirinixic Acid)

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0829
    CAS #: 50892-23-4Purity ≥98%

    Description: Pirinixic Acid (also known as NSC 310038; NSC310038; WY-14643; WY 14643) is a novel, highly potent and selective peroxisome proliferator and activator of PPARα with important biological activity. It inhibits PPARα with an EC50 of 1.5 μM.  Pirinixic Acid was under development for preventing severe cardiac dysfunction, cardiomyopathy and heart failure as a result of lipid accumulation within cardiac myocytes. 

    References: Nature. 1990 Oct 18;347(6294):645-50; Nature. 1998 Jun 25;393(6687):790-3; FASEB J. 2002 Jul;16(9):1027-40.

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    Molecular Weight (MW)323.8
    FormulaC14H14ClN3O2S
    CAS No.50892-23-4
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 65 mg/mL (200.7 mM)
    Water: <1 mg/mL
    Ethanol: 65 mg/mL (200.7 mM)
    Other info

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

    InChi Key: SZRPDCCEHVWOJX-UHFFFAOYSA-N

    InChi Code: 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)

    SMILES Code: O=C(O)CSC1=NC(NC2=CC=CC(C)=C2C)=CC(Cl)=N1           

    SynonymsNSC 310038; NSC310038; WY-14643; WY 14643; NSC-310038; WY14643; Pirinixic Acid


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    In Vitro

    In vitro activity: WY 14643 (10 μM) almost completely inhibits interleukin-1-induced production of interleukin-6 and prostaglandin and expression of cyclooxygenase-2 in aortic smooth-muscle cells, through repression of NF-κB signaling. WY14643 (250 μM) reduces VCAM-1 expression levels significantly, to 52 % of TNF-α-stimulated human endothelial cells. Pretreatment of endothelial cells with WY 14643 (10 μM) before TNF-α stimulation reduces U937 cell adhesion by 50%.


    Kinase Assay: Pirinixic acid (Wy-14643) is a potent 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. 


    Cell Assay: Synovial fibroblasts are treated with LPS (100 μg/mL) in the presence or absence of Pirinixic acid. PPAR-α siRNA-transfected cells are also treated with LPS (100 μg/mL) together with Pirinixic acid. After stimulation, the production of NO is determined using Griess reagents. Briefly, 300 μL of supernatant is mixed with 100 μL of Griess reagent and 2.6 mL of deionized water. The mixture is incubated for 30 min at room temperature, and the absorbance at 548 nm is measured. The concentrations of NO in the supernatants are calculated from a standard curve

    In VivoWY 14643 (1 mg/kg i.v. bolus) administration at 30 min before left anterior descending occlusion, causes significant reduction in infarct size of ∼44% in rats subjected to regional myocardial ischemia (25 min) and reperfusion (2 h). WY 14643 (3 mg/kg) lowers basal plasma levels of glucose, triglycerides (-16% vs. untreated), and leptin (-52%), and also muscle triglyceride (-34%) and total long-chain acyl-CoAs (LCACoAs) (-41%) in high fat-fed rats. WY14643 substantially reduces visceral fat weight and total liver triglyceride content without increasing body weight gain. WY14643 enhances whole body insulin sensitivity (clamp glucose infusion rate increases 35% and glucose disposals 22%, vs. untreated). WY 14643 enhances insulin-mediated muscle glucose metabolic index (Rg') in red (47%) and white (63%) muscles as well as in white adipose tissue (90%), and reduces muscle triglyceride and LCACoA accumulation.
    Animal modelRats
    Formulation & Dosage1 mg/kg i.v. bolus
    References

    Nature. 1990 Oct 18;347(6294):645-50; Nature. 1998 Jun 25;393(6687):790-3; FASEB J. 2002 Jul;16(9):1027-40.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

    WY-14643 (Pirinixic Acid)


    Histopathological changes from lung tissue, showing the effects of LPS with Wy-14643 on WT and PPARα null mice. Biochem Biophys Res Commun. 2013 Jul 5;436(3):366-71. 
     

    WY-14643 (Pirinixic Acid)


    Evaluation of apoptosis using TUNEL assays from lung sections in WT and Pparα-null mice with Wy-14643 and/or LPS. Biochem Biophys Res Commun. 2013 Jul 5;436(3):366-71. 
     

    WY-14643 (Pirinixic Acid)


    Evaluation of 3-nitrotyrosine levels and lipid peroxdiation in WT and PPARα null mice with Wy-14643 and/or LPS. Biochem Biophys Res Commun. 2013 Jul 5;436(3):366-71. 


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