Muraglitazar

Muraglitazar is a dual agonist of peroxisome proliferator-activated receptor α (PPARα) and PPARγ (EC₅₀s = 0.32 and 0.11 μM, respectively).¹ It is selective for PPARα/γ over other nuclear receptors, including PPARδ, RXRα, RARs, estrogen receptor α (ERα), ERβ, androgen receptor (AR), and progesterone receptor (PR). Muraglitazar (50 μM) reduces the size of lipid droplets in oleic acid-treated HepaRG human hepatocytes.² It reduces plasma levels of glucose, triglycerides, free fatty acids, and insulin by 54, 33, 62, and 48%, respectively, in db/db mice when administered at a dose of 10 mg/kg per day.¹ Muraglitazar (10 mg/kg per day) reduces plasma levels of glucose, triglycerides, and cholesterol in diet-induced obese mice.³ Muraglitazar also inhibits LPS-induced increases in nitric oxide (NO) production and IL-6, TNF-α, and inducible nitric oxide synthase (iNOS) protein levels in J774 murine macrophages in a concentration-dependent manner.⁴ It inhibits carrageenan-induced paw edema in mice when administered at doses ranging from 12.5 to 50 mg/kg.

WARNING This product is not for human or veterinary use.

1. Devasthale, P.V., Chen, S., Jeon, Y., et al. Design and synthesis of N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine [Muraglitazar/BMS-298585], a novel peroxisome proliferator-activated receptor α/γ dual agonist with efficacious glucose and lipid-lowering activities. J. Med. Chem. 48, 2248-2250 (2005).

2. Rogue, A., Anthérieu, S., Vluggens, A., et al. PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells. Toxicol. Appl. Pharmacol. 276(1), 73-81 (2014).

3. Harrity, T., Farrelly, D., Tieman, A., et al. Muraglitazar, a novel dual (α/γ) peroxisome proliferator-activated receptor activator, improves diabetes and other metabolic abnormalities and preserves β-cell function in db/db mice. Diabetes 55(1), 240-248 (2006).

4. Paukkeri, E.-L., Leppänen, T., Lindholm, M., et al. Anti-inflammatory properties of a dual PPARgamma/alpha agonist muraglitazar in in vitro and in vivo models. Arthritis Res. Ther. 15(2):R51, (2013).