A potent antihypercholesterolemic agent: [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14643)

Santilli, Arthur A.; Scotese, Anthony C.; Tomarelli, R. M.

doi:10.1007/bf01923636

Cited by 52 publications

(29 citation statements)

References 2 publications

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“…These results suggest that the effect of 15d-PGJ 2 may be mediated through a mechanism independent on PPAR-γ . Specific PPAR-α agonist WY14643 (Santilli et al 1974) was inert. Anti-inflammatory steroid DEX had a synergistic effect on the inhibition of GM-CSF expression by 15d-PGJ 2 .…”

Section: Discussionmentioning

confidence: 99%

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15-Deoxy-.DELTA.12,14-Prostaglandin J2 Inhibits the IL-1.BETA.-Induced Expression of Granulocyte-Macrophage Colony-Stimulating Factor in BEAS-2B Bronchial Epithelial Cells

Kumagai¹,

Imaizumi²,

Yoshida³

et al. 2004

Tohoku J. Exp. Med.

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Section: Discussionmentioning

confidence: 99%

“…The control cells were treated with vehicle only. The effects of specific PPAR-α agonist WY14643 (Santilli et al 1974) or PPAR-γ agonist ciglitazone (Sohda et al 1982) on the IL-1β -induced GM-CSF expression were examined in a similar manner. WY14643 and ciglitazone were also dissolved in ethanol.…”

Section: Cellsmentioning

confidence: 99%

15-Deoxy-.DELTA.12,14-Prostaglandin J2 Inhibits the IL-1.BETA.-Induced Expression of Granulocyte-Macrophage Colony-Stimulating Factor in BEAS-2B Bronchial Epithelial Cells

Kumagai¹,

Imaizumi²,

Yoshida³

et al. 2004

Tohoku J. Exp. Med.

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“…The WY-14643 (pirinixic acid) is a failed drug as an anti-hypercholesterolemic agent [14], which is known to cause hepatotoxicity such as carcinogenicity at liver in rodents. It is well known that this compound is a selective agonist of Peroxisome Proliferator-Activated Receptor alpha (PPARα).…”

Section: Case Study: Molecular Mechanism Of Wy-14643 Hepatotoxicitymentioning

confidence: 99%

Integrated toxicogenomics analysis with Toxygates for inferring molecular mechanisms

Natsume-Kitatani

Nyström-Persson

Igarashi

et al. 2017

Genomics Comput Biol

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Assessment of the safety of drug candidates in early research and development (R&D) stage holds the key to the successful drug development. Toxicogenomics is one of the promising approaches using omics techniques since a number of ‘omics databases is rapidly growing. Although many of these databases are open to the public, there remain some barriers for biologists regardless of their bioinformatics skills. Toxygates was originally developed as a user-friendly interface for Open TG-GATEs, which is one of the largest and most widely used toxicogenomics databases. Since the original Toxygates was developed to enable users to display the gene expression values obtained by selected compounds or experimental conditions for genes of interest, there were some limitations as an analytical platform. To overcome this situation, significant improvements have been added and finally, a new version of Toxygates allows users to analyze the data such as creating heatmap for visualization of gene expression profile, performing hierarchical clustering and creating a dendrogram with interactive display, performing several types of enrichment analysis such as gene ontology and pathways and uploading user data for further analysis. As a case study, we used Toxygates to successfully find novel insights that the hepatotoxicity caused by well-studied PPARα agonist WY-14643 may include the disruption of intracellular calcium dynamics and imbalance between PPARα signaling and Wnt signaling.

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“…Santilli et al (1974) reported that Wy14,643 was more potent than clofibrate, a drug known to reduce serum lipid levels. Although their data demonstrated a reduction of greater than 50% in blood cholesterol levels, D 'Atri et al (1980) subsequently showed that Wy14,643 only minimally affected cholesterol levels in SpragueDawley rats placed on a cholesterol-enriched diet.…”

Section: P Zahradkamentioning

confidence: 99%

Cardiovascular Actions of the Peroxisome Proliferator‐Activated Receptor‐Alpha (PPARα) Agonist Wy14,643

Zahradka

2007

Cardiovascular Drug Reviews

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This review examines the various effects of Wy14,643, a hypolipidemic agent that activates peroxisome proliferator-activated receptor-α (PPARα), on the cardiovascular system. An emphasis has been placed on the specific cellular processes affected by Wy14,643 as they relate to vascular and cardiac function. Although the topic of this discussion is limited to vascular and cardiac tissues, the importance of circulating lipids on cardiovascular disease requires that a description of the indirect actions of this compound on liver metabolism also be included. Finally, the pharmacology of Wy14,643 is discussed within the context of PPARα-dependent and -independent mechanisms.

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A potent antihypercholesterolemic agent: [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14643)

Cited by 52 publications

References 2 publications

15-Deoxy-.DELTA.12,14-Prostaglandin J2 Inhibits the IL-1.BETA.-Induced Expression of Granulocyte-Macrophage Colony-Stimulating Factor in BEAS-2B Bronchial Epithelial Cells

15-Deoxy-.DELTA.12,14-Prostaglandin J2 Inhibits the IL-1.BETA.-Induced Expression of Granulocyte-Macrophage Colony-Stimulating Factor in BEAS-2B Bronchial Epithelial Cells

Integrated toxicogenomics analysis with Toxygates for inferring molecular mechanisms

Cardiovascular Actions of the Peroxisome Proliferator‐Activated Receptor‐Alpha (PPARα) Agonist Wy14,643

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