Pemafibrate

Pemafibrate is an orally bioavailable and selective agonist of peroxisome proliferator-activated receptor α (PPARα; EC₅₀ = 1 nM for transcriptional activity), a transcription factor that is essential for regulation of lipid homeostasis.¹ It is selective for PPARα over PPARδ and PPARγ (EC₅₀s = 2,300 and 1,000 nM, respectively, for transcriptional activity). In human HepG2 hepatoma cells, pemafibrate is 1,000-fold more potent than the classical PPARα agonists fenofibrate (Item No. 10005368) and Wy 14643 (Item No. 70730) in activating PPARα transcriptional activity.² Pemafibrate (0.001% w/w) reduces plasma triglyceride levels, non-esterified fatty acids, and total cholesterol in mice fed a moderate-fat diet, and, when administered at 0.00025%, it reduces liver lipid accumulation and improves prognosis in wild-type but not Ppara knockout mice in a model of diet-induced non-alcoholic fatty liver disease (NAFLD).² In mouse models of non-alcoholic steatohepatitis (NASH), pemafibrate stimulates expression of PPARα, enhances lipid turnover, and reduces liver triglyceride levels and inflammation.³ It also dose-dependently reduces the area of atherosclerotic lesions in human apolipoprotein E2 (ApoE2) knock-in mice.⁴

WARNING This product is not for human or veterinary use.

1. Fruchart, J.C. Selective peroxisome proliferator-activated receptor α modulators (SPPARMα): The next generation of peroxisome proliferator-activated receptor α-agonists. Cardiovasc. Diabetol. 12, 82 (2013).

2. Takei, K., Han, S.I., Murayama, Y., et al. Selective peroxisome proliferator-activated receptor-α modulator K^-877 efficiently activates the peroxisome proliferator-activated receptor-α pathway and improves lipid metabolism in mice. J. Diabetes Investig. 8(4), 446-452 (2017).

3. Honda, Y., Kessoku, T., Ogawa, Y., et al. Pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, improves the pathogenesis in a rodent model of nonalcoholic steatohepatitis. Sci. Rep. 7, 42477 (2017).

4. Hennuyer, N., Duplan, I., Paquet, C., et al. The novel selective PPARα modulator (SPPARMα) pemafibrate improves dyslipidemia, enhances reverse cholesterol transport and decreases inflammation and atherosclerosis. Atherosclerosis 249, 200-208 (2016).