WY-14643 (Pirinixic Acid) (Synonyms: NSC 310038, Pirinixic Acid)

Cell lines

Human ECs and U937 cells

Preparation method

The solubility of this compound in DMSO is > 16.2 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.

Reacting condition

0, 2.5, 25 or 250 μM; 24 hrs

Applications

Pretreatment of ECs with 250 μM WY-14643 significantly down-regulated the VCAM-1 expression level to 52 ± 2% of TNF-α-stimulated cells. Besides, pretreatment of ECs with WY-14643 before TNF-α stimulation significantly reduced U937 cell adhesion to 37.3 ± 4.3 × 103 cells/cm2. Northern blot analysis indicated that the increased VCAM-1 mRNA level caused by TNF-α stimulation could be concentration-dependently inhibited by pretreatment with WY-14643.

Animal models

High fat-fed rats

Dosage form

3 mg/kg/day; p.o.; for 2 weeks

Applications

In high fat-fed rats, WY-14643 lowered basal plasma levels of glucose, triglycerides and leptin, muscle triglyceride as well as total LCACoAs. Besides, WY-14643 significantly reduced visceral fat weight and total liver triglyceride content, without increasing body weight gain. In addition, WY-14643 enhanced whole body insulin sensitivity, thus increasing insulin-mediated muscle glucose metabolic index in red and white muscles as well as in white adipose tissue, and reducing muscle triglyceride as well as LCACoA accumulation.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Marx N, Sukhova GK, Collins T, Libby P, Plutzky J. PPARalpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation. 1999 Jun 22;99(24):3125-31.

[2]. Ye JM, Doyle PJ, Iglesias MA, Watson DG, Cooney GJ, Kraegen EW. Peroxisome proliferator-activated receptor (PPAR)-alpha activation lowers muscle lipids and improves insulin sensitivity in high fat-fed rats: comparison with PPAR-gamma activation. Diabetes. 2001 Feb;50(2):411-7.