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Chemical Structure| 50892-23-4 Chemical Structure| 50892-23-4

Structure of Pirinixic Acid
CAS No.: 50892-23-4

Chemical Structure| 50892-23-4

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Wy-14643 is an agonist of PPARα with EC50 of 0.63 μM that can decrease the inflammatory response. It has other functions including lipid metabolism, cell proliferation, differentiation, adipogenesis etc..

Synonyms: Wy-14643; NSC 310038

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Product Details of Pirinixic Acid

CAS No. :50892-23-4
Formula : C14H14ClN3O2S
M.W : 323.80
SMILES Code : O=C(O)CSC1=NC(NC2=CC=CC(C)=C2C)=CC(Cl)=N1
Synonyms :
Wy-14643; NSC 310038
MDL No. :MFCD00191335
InChI Key :SZRPDCCEHVWOJX-UHFFFAOYSA-N
Pubchem ID :5694

Safety of Pirinixic Acid

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Primary cardiomyocytes 10 µM 12 hours Inhibition of p53 significantly enhanced mitochondrial basal respiration Theranostics. 2021 Mar 4;11(10):4710-4727.
H9C2 cells 30 µM 2 hours Induced cell senescence, results showed enhanced p53 expression and decreased Rap1 expression Theranostics. 2021 Mar 4;11(10):4710-4727.
Hippocampal neurons 25 µM 24 hours Induced the expression of ADAM10, increased the release of sAPPα, and reduced Aβ production Proc Natl Acad Sci U S A. 2015 Jul 7;112(27):8445-50.
HEK293-AβPPwt cells 0.1 µM 24 hours To evaluate the effect of MH84 on mitochondrial mass, results showed that MH84 increased mitochondrial mass in treated cells Alzheimers Res Ther. 2018 Feb 13;10(1):18.
HEK293-AβPPsw cells 0.1 µM 24 hours To evaluate the effect of MH84 on mitochondrial mass, results showed that MH84 increased mitochondrial mass in treated cells Alzheimers Res Ther. 2018 Feb 13;10(1):18.
HepG2 cells 20 µM 48 hours To study the interaction between PPARα and YAP and the nuclear translocation of YAP Hepatology. 2022 Jan;75(1):74-88.
Mouse pulmonary microvascular endothelial cells 1 µM 48 hours To evaluate cell proliferation, results showed that EET analogs significantly stimulated the proliferation of Cyp2c44 KO endothelial cells. Cancer Res. 2014 Jan 15;74(2):621-31.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice KRasLA2 mouse model Drinking water 0.02% Wy-14643 Continuous administration from 1 to 3 months or 3 to 5 months To evaluate the effect of Wyeth-14,643 on primary lung cancer growth, results showed that Wyeth-14,643 significantly reduced the number and size of lung cancer. Cancer Res. 2014 Jan 15;74(2):621-31.
Mice Mycfl/fl and Mycfl/fl,ERT2-Cre mice Oral 0.1% Wy-14,643 Once daily for two weeks To investigate the role of Myc in hepatocellular proliferation, results showed that Mycfl/fl,ERT2-Cre mice had significantly reduced hepatocellular proliferation J Hepatol. 2014 Feb;60(2):331-8
Mice Hepatocyte-specific Myc knockout mice (MycΔHep) Oral 0.1% Wy-14643 Daily for two days To investigate the amplification effect of MYC on Krt23 expression after PPARA activation, it was found that Krt23 was significantly upregulated in wild-type mice but significantly attenuated in MycΔHep mice. Hepatology. 2019 Jul;70(1):154-167
Mice C57BL/6J background mice Oral 0.1% WY-14643 24 or 48 hours To investigate the effect of PPARα activation on the expression of lncRNA Gm15441 in mouse liver and its impact on inflammasome activation. Results showed that PPARα activation significantly induced Gm15441 expression and reduced NLRP3 inflammasome activation by suppressing TXNIP expression. Nat Commun. 2020 Nov 17;11(1):5847
Mice Rap1-/- mice Intraperitoneal injection 1.1 mg/kg/day Once daily for 6 weeks Inhibition of p53 improved cardiac fatty acid metabolism and restored cardiac function Theranostics. 2021 Mar 4;11(10):4710-4727.
Mice Lieber-DeCarli model Diet 10 mg/L Continued for 18 or 25 days WY-14,643 enhanced ethanol metabolism and escalated ethanol clearance via a PPARα-PEX16-ACOX-catalase network. Free Radic Biol Med. 2023 Nov 1;208:221-228
C57BL/6J mice Chronic ethanol feeding model Oral 10 mg/L 3 weeks WY-14,643 ameliorates ethanol and nicotine-induced fatty liver through induction of peroxisome proliferator-activated receptor α (PPARα) pathways, but it also enhances ethanol and nicotine-induced liver injury. WY-14,643 escalates ethanol metabolism by inducing catalase. Free Radic Biol Med. 2021 Jun;169:283-293
C57BL/6 mice PPAR α activation-induced hepatomegaly model Intraperitoneal injection 100 mg/kg/d Once daily for 1, 2, 3, 5, or 10 days To investigate PPAR α activation-induced hepatomegaly and its zonal distribution characteristics, it was found that PPAR α activation mainly caused hepatocyte hypertrophy around the central vein area and hepatocyte proliferation around the portal vein area. Acta Pharmacol Sin. 2023 Oct;44(10):2037-2047
C57BL/6 mice Wild-type mice and PparaΔHep mice 100 mg/kg/day Once daily for 10 days To investigate the effect of PPARα activation on hepatomegaly and liver regeneration, results showed that PPARα activation significantly induced hepatomegaly and accelerated liver regeneration Hepatology. 2022 Jan;75(1):74-88.
C57BL/6 mice Thy-1 AβPPSL mouse model Oral gavage 12 mg/kg Once daily for 21 days To evaluate the effect of MH84 on mitochondrial dysfunction in a mouse model of early Alzheimer's disease, results showed that MH84 improved mitochondrial function and reduced β-secretase-related C99 peptide and Aβ40 levels Alzheimers Res Ther. 2018 Feb 13;10(1):18.
Rats Nicotine self-administration model Intraperitoneal injection 20 or 40 mg/kg 20 minutes before each session, for 3 consecutive days To evaluate the effect of PPAR-α agonists on nicotine self-administration behavior, results showed that PPAR-α agonists significantly reduced nicotine self-administration. Biol Psychiatry. 2011 Apr 1;69(7):633-41
Mice ApoE-/- mice Oral 5 mg/day/mice For 4 weeks To evaluate the effect of LP105 on aortic aneurysm development, results showed that LP105 significantly attenuated vascular remodeling and aortic aneurysm formation. Br J Pharmacol. 2011 Aug;163(8):1721-32
Mice ANIT-induced cholestasis model Oral 5, 25, 125 mg/kg Twice daily for 5 days To evaluate the protective effect of feno?brate against ANIT-induced cholestasis and liver injury. The results showed that feno?brate exerted its protective effect by inhibiting the JNK signaling pathway, and this protection was dependent on PPARα and the dose of feno?brate. Br J Pharmacol. 2017 Sep;174(18):3000-3017
Zebrafish embryo Zebrafish embryo model Water exposure 51.8 μM 96 hours The uptake kinetics and biotransformation of Pirinixic Acid in zebrafish embryos were studied, revealing that its internal concentration was 89.7 times lower than predicted, and 6 transformation products were identified. Environ Sci Technol. 2024 Oct 8;58(40):17898-17907

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.09mL

0.62mL

0.31mL

15.44mL

3.09mL

1.54mL

30.88mL

6.18mL

3.09mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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