Pemafibrate ((R)-K-13675) is a highly specific PPARα agonist (EC50: 1 nM).

PPARγ (human):1.1 μM (EC50), PPARα (human):1 nM (EC50), PPARδ:1.58 μM (EC50)

Pemafibrate is a potent PPARα agonist, with EC50 values of 1 nM for h-PPARα, 1.10 μM for h-PPARγ, and 1.58 μM for h-PPARδ.

Pemafibrate (3 mg/kg, p.o.) increases plasma h-apoA-I in human apoA-I (h-apoA-I) transgenic mice and shows higher levels of plasma h-apoA-I than fenofibrate at 300 mg/kg [1]. At 0.03 mg/kg, pemafibrate reduces triglycerides and aspartate aminotransferase (AST) levels in PEMA-L (db/db) mice, while at 0.1 mg/kg, it also increases liver weight in PEMA-H (db/db) mice and enhances pathogenesis in a rodent model of nonalcoholic steatohepatitis (NASH), significantly reducing hepatocyte ballooning in PEMA-H mice [2]. Pemafibrate (K-877, 0.0005%) in a high-fat diet (HFD) inhibits weight gain in mice and significantly decreases the abundance of triglyceride (TG)-rich lipoproteins, including remnants, in postprandial plasma. It also decreases intestinal mRNA expression of ApoB and Npc1l1 [3].

Mice are fasted for 12?h and fasting blood glucose measured. Nine-week-old db/db mice are used in the assay. After a 2-week acclimatization period, mice are divided into four groups: BD (db/db) mice (fed basal diet (BD) and treated with 0.5% aqueous methylcellulose solution (MC); MCD (db/db) mice (fed methionine choline-deficient (MCD) and treated with 0.5% MC); PEMA-L (db/db) mice (fed MCD and treated with 0.03?mg/kg Pemafibrate); PEMA-H (db/db) mice (fed MCD and treated with 0.1?mg/kg Pemafibrate). The drug-free solvent or the dosing solution is administered to animals (5?mL/kg body weight, p.o.) once daily (in the morning) for 4 consecutive weeks. After a 2-week acclimatization period, BD mice are fed a BD for 20 weeks. CTRL mice are fed D09100301 for 20 weeks. PEMA-L and PEMA-H mice are fed D09100301 for 12 weeks followed by D09100301 with 0.4?mg and 1.3?mg Pemafibrate/kg of the diet for 8 weeks, which corresponds to 0.03?mg/kg/day and 0.1?mg/kg/day, respectively. FENO mice are fed D09100301 for 12 weeks followed by D09100301 with 666.7?mg fenofibrate/kg of the diet for 8 weeks, which corresponds to 50?mg/kg/day. Pemafibrate and fenofibrate are incorporated into the AMLN diet. Animals are housed under conventional conditions with controlled temperature, humidity, and light (12-h light-dark cycle) and provided with food and water [2].

H2O: Insoluble

DMSO: 100 mg/mL (203.85 mM), Sonication is recommended.

10% DMSO+40% PEG300+5% Tween 80+45% Saline: 4 mg/mL (8.15 mM), Sonication is recommended.