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Details

Stereochemistry ACHIRAL
Molecular Formula C14H14ClN3O2S
Molecular Weight 323.7994
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PIRINIXIC ACID

SMILES

Cc1cccc(c1C)N=c2cc(Cl)nc([nH]2)SCC(=O)O

InChI

InChIKey=SZRPDCCEHVWOJX-UHFFFAOYSA-N
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)

HIDE SMILES / InChI
Molecular Formula C14H14ClN3O2S
Molecular Weight 323.7994
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/21585347 https://en.wikipedia.org/wiki/Pirinixic_acid

Pirinixic acid is a PPARα ligand that can affect atherogenesis by modulating hepatic lipid metabolism and by acting directly on vascular tissue. PPARα activation is generally assumed to be the primary means by which Pirinixic acid produces its biological effects. Nevertheless, there is increasing evidence to suggest that Pirinixic acid is also capable of affecting cellular processes directly. It is under experimental investigation for prevention of severe cardiac dysfunction, cardiomyopathy and heart failure as a result of lipid accumulation within cardiac myocytes. Treatment is primarily aimed at individuals with an adipose triglyceride lipase (ATGL) enzyme deficiency or mutation. For example, cardiac contractility was improved by treating ATGL(-/-) mice with the Pirinixic acid.

CNS Activity

CNS Penetrant
1174
Curator's Comment:: pirinixic acid in an esterified form

Originator

Approval Year

Unknown
28299
Targets

Targets

Primary TargetPharmacologyConditionPotency
Agonist
1109
 5.38 µM [EC50]
Agonist
1109
 17.0 mM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
trans-Activation of PPARalpha and PPARgamma by structurally diverse environmental chemicals.
1999 Dec 1
Evidence for direct binding of fatty acids and eicosanoids to human peroxisome proliferators-activated receptor alpha.
1999 Jul 14
Effects of fibrate compounds on expression of plasminogen activator inhibitor-1 by cultured endothelial cells.
1999 Jun
Activators of peroxisome proliferator-activated receptor-alpha induce the expression of the uncoupling protein-3 gene in skeletal muscle: a potential mechanism for the lipid intake-dependent activation of uncoupling protein-3 gene expression at birth.
1999 Jun
The PPARs: from orphan receptors to drug discovery.
2000 Feb 24
Identification of novel peroxisome proliferator-activated receptor alpha (PPARalpha) target genes in mouse liver using cDNA microarray analysis.
2001
Effects of peroxisome proliferators on antioxidant enzymes and antioxidant vitamins in rats and hamsters.
2001 Apr
Differential regulation of expression of genes encoding uncoupling proteins 2 and 3 in brown adipose tissue during lactation in mice.
2001 Apr 1
PPARalpha-dependent induction of liver microsomal esterification of estradiol and testosterone by a prototypical peroxisome proliferator.
2001 Aug
Peroxisome proliferator-activated receptor-alpha ligands inhibit cardiac lipoprotein lipase activity.
2001 Aug
Effects of bezafibrate on beta-cell function of rat pancreatic islets.
2001 Aug 31
Differential regulation of adipocytokine mRNAs by rosiglitazone in db/db mice.
2001 Aug 31
Activators of peroxisome proliferator-activated receptors protect human skin from ultraviolet-B-light-induced inflammation.
2001 Dec
Peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, WY-14,643, increased transcription of myosin light chain-2 in cardiomyocytes.
2001 Dec
Selective modification of pyruvate dehydrogenase kinase isoform expression in rat pancreatic islets elicited by starvation and activation of peroxisome proliferator-activated receptor-alpha: implications for glucose-stimulated insulin secretion.
2001 Dec
The transcription of the peroxisome proliferator-activated receptor alpha gene is regulated by protein kinase C.
2001 Dec 15
Effects of peroxisome proliferators on glutathione and glutathione-related enzymes in rats and hamsters.
2001 Feb 15
Abundant expression of uncoupling protein-2 in the small intestine: up-regulation by dietary fish oil and fibrates.
2001 Jan 15
Fatty-acyl-CoA thioesters inhibit recruitment of steroid receptor co-activator 1 to alpha and gamma isoforms of peroxisome-proliferator-activated receptors by competing with agonists.
2001 Jan 15
PPARalpha activators inhibit tissue factor expression and activity in human monocytes.
2001 Jan 16
PPARalpha agonists inhibit tissue factor expression in human monocytes and macrophages.
2001 Jan 16
Inhibitors of arachidonic acid metabolism potentiate tumour necrosis factor-alpha-induced apoptosis in HL-60 cells.
2001 Jul 13
Identification of a peroxisome-proliferator-activated-receptor response element in the apolipoprotein E gene control region.
2001 Jul 15
Unique renal tubule changes induced in rats and mice by the peroxisome proliferators 2,4-dichlorophenoxyacetic acid (2,4-D) and WY-14643.
2001 Jul-Aug
Mechanisms of extrahepatic tumor induction by peroxisome proliferators in male CD rats.
2001 Mar
Limited cooperation between peroxisome proliferator-activated receptors and retinoid X receptor agonists in sebocyte growth and development.
2001 Nov
Fibrates suppress bile acid synthesis via peroxisome proliferator-activated receptor-alpha-mediated downregulation of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase expression.
2001 Nov
Activation of the peroxisome proliferator-activated receptor-alpha enhances cell death in cultured cerebellar granule cells.
2001 Oct 15
Peroxisome proliferator-activated receptor-alpha regulates lipid homeostasis, but is not associated with obesity: studies with congenic mouse lines.
2001 Oct 19
Phenobarbital, oxazepam and Wyeth 14,643 cause DNA damage as measured by the Comet assay.
2001 Sep
Adaptive increase in pyruvate dehydrogenase kinase 4 during starvation is mediated by peroxisome proliferator-activated receptor alpha.
2001 Sep 21
Negative regulation of human fibrinogen gene expression by peroxisome proliferator-activated receptor alpha agonists via inhibition of CCAAT box/enhancer-binding protein beta.
2001 Sep 7
Nimesulide, a preferential cyclooxygenase 2 inhibitor, suppresses peroxisome proliferator-activated receptor induction of cyclooxygenase 2 gene expression in human synovial fibroblasts: evidence for receptor antagonism.
2002 Feb
Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin.
2002 Feb
The role of hepatocyte RXR alpha in xenobiotic-sensing nuclear receptor-mediated pathways.
2002 Feb
Characterization of an acyl-coA thioesterase that functions as a major regulator of peroxisomal lipid metabolism.
2002 Jan 11
PPARalpha and PPARdelta activators inhibit cytokine-induced nuclear translocation of NF-kappaB and expression of VCAM-1 in EAhy926 endothelial cells.
2002 Jan 25
Microarray analysis of gene expression changes in mouse liver induced by peroxisome proliferator- activated receptor alpha agonists.
2002 Jan 25
Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size.
2002 Jul
WY14,643, a peroxisome proliferator-activated receptor alpha (PPARalpha ) agonist, improves hepatic and muscle steatosis and reverses insulin resistance in lipoatrophic A-ZIP/F-1 mice.
2002 Jul 5
Mechanism for peroxisome proliferator-activated receptor-alpha activator-induced up-regulation of UCP2 mRNA in rodent hepatocytes.
2002 Mar 15
Differential effects of gemfibrozil on migration, proliferation and proteoglycan production in human vascular smooth muscle cells.
2002 May
Selective inhibition of cyclooxygenase-2 expression by 15-deoxy-Delta(12,14)(12,14)-prostaglandin J(2) in activated human astrocytes, but not in human brain macrophages.
2002 May 1
Involvement of the peroxisome proliferator-activated receptor alpha in the immunomodulation caused by peroxisome proliferators in mice.
2002 May 15
Inhibition of cytokine-induced matrix metalloproteinase 9 expression by peroxisome proliferator-activated receptor alpha agonists is indirect and due to a NO-mediated reduction of mRNA stability.
2002 Sep 6
Patents

Patents

US6060515A
1

Sample Use Guides

In Vivo Use Guide
0.02% w/w in food over 10 days or 0.1% w/w for 7 days. intraperitoneal injection - 50 mg/kg or 80 mg/kg
Route of Administration: Other
In Vitro Use Guide
Mitochondria from the left ventricle of rats were similarly sensitive to 100 µM Wy14,643. In this case Wy14,643 inhibited state 3 respiration, which affected both respiratory capacity and the ADP phosphorylation state. As a result, oxidative phosphorylation is uncoupled by Wy14,643.
Substance Class Chemical
Created
by admin
on Sat Jun 26 02:53:47 UTC 2021
Edited
by admin
on Sat Jun 26 02:53:47 UTC 2021
Record UNII
86C4MRT55A
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PIRINIXIC ACID
INN  
INN  
Official Name English
WY-14643
Code English
(4-CHLORO-6-(2,3-XYLIDINO)-2-PYRIMIDINYLTHIO)ACETIC ACID
Systematic Name English
NSC-310038
Code English
PIRINIXIC ACID [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C45175
Created by admin on Sat Jun 26 02:53:48 UTC 2021 , Edited by admin on Sat Jun 26 02:53:48 UTC 2021
Code System Code Type Description
FDA UNII
86C4MRT55A
Created by admin on Sat Jun 26 02:53:48 UTC 2021 , Edited by admin on Sat Jun 26 02:53:48 UTC 2021
PRIMARY
CAS
50892-23-4
Created by admin on Sat Jun 26 02:53:48 UTC 2021 , Edited by admin on Sat Jun 26 02:53:48 UTC 2021
PRIMARY
MESH
C006253
Created by admin on Sat Jun 26 02:53:48 UTC 2021 , Edited by admin on Sat Jun 26 02:53:48 UTC 2021
PRIMARY
NCI_THESAURUS
C29866
Created by admin on Sat Jun 26 02:53:48 UTC 2021 , Edited by admin on Sat Jun 26 02:53:48 UTC 2021
PRIMARY
EVMPD
SUB09915MIG
Created by admin on Sat Jun 26 02:53:48 UTC 2021 , Edited by admin on Sat Jun 26 02:53:48 UTC 2021
PRIMARY
INN
4871
Created by admin on Sat Jun 26 02:53:48 UTC 2021 , Edited by admin on Sat Jun 26 02:53:48 UTC 2021
PRIMARY
PUBCHEM
5694
Created by admin on Sat Jun 26 02:53:48 UTC 2021 , Edited by admin on Sat Jun 26 02:53:48 UTC 2021
PRIMARY
ChEMBL
CHEMBL295416
Created by admin on Sat Jun 26 02:53:48 UTC 2021 , Edited by admin on Sat Jun 26 02:53:48 UTC 2021
PRIMARY
EPA CompTox
50892-23-4
Created by admin on Sat Jun 26 02:53:48 UTC 2021 , Edited by admin on Sat Jun 26 02:53:48 UTC 2021
PRIMARY
HSDB
8056
Created by admin on Sat Jun 26 02:53:48 UTC 2021 , Edited by admin on Sat Jun 26 02:53:48 UTC 2021
PRIMARY
Related Record Type Details
OATP1B1
TRANSPORTER -> INHIBITOR
Related Record Type Details
Structure of PIRINIXIC ACID
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