Description
Muraglitazar is a dual agonist of peroxisome proliferator-activated receptor α (PPARα) and PPARγ (EC50s = 0.32 and 0.11 μM, respectively). 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. 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. Muraglitazar (10 mg/kg per day) reduces plasma levels of glucose, triglycerides, and cholesterol in diet-induced obese mice. 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. It inhibits carrageenan-induced paw edema in mice when administered at doses ranging from 12.5 to 50 mg/kg.
Chemical Properties
Off-White Solid
Uses
It is a peroxisome proliferator-activated receptor (PPAR) a/ dual agonist
Uses
It is a peroxisome proliferator-activated receptor (PPAR) α/γ dual agonist.
Definition
ChEBI: Muraglitazar is a member of 1,3-oxazoles.
in vitro
in murine j774 macrophages, muraglitazar dose-dependently reduced lipopolysaccharide-induced inducible nitric oxide synthase (inos) expression, nitrous oxide, il-6 and tnfα production and showed no effect on cell viability at the given concentration. muraglitazar decreased the levels of inos mrna expression, suggesting that the suppressive effect of muraglitazar was mediated at the level of inos transcription. in human hek293 cells, muraglitazar did not affect the nuclear levels of nf- κb p65 compared to the control and did not modulate nf-κb-mediated transcription [1].
in vivo
male charles river mice were administrated orally with muraglitazar at a dose of 12.5, 25, 50 mg/kg for six hours. muraglitazar, in a dose-dependent fashion, prevented the development of oedema. in addition, muraglitazar dose-dependently attenuated inflammation and decreased the levels of il-6, tnfα and inos mrna [1].
IC 50
0.42 μm: shows agonistic activity at peroxisome proliferator-activated receptor α (pparα)
References
[1]. paukkeri, e., leppnen, t., lindholm, m., yam, m., asmawi, m., & kolmonen, a. et al. anti-inflammatory properties of a dual ppargamma/alpha agonist muraglitazar in in vitro and in vivo models. arthritis research & therapy. 2013;15(2): r51.
