Seladelpar sodium salt

Cell experiment:

Human PPARδ, PPARα and PPARγ activity is monitored in transiently transfected cells treated with increasing concentrations of MBX-8025 (0.1 nM, 1 nM, 10 nM, 100, nM, 1000 nM) in comparison with reference compounds (0.1 nM-1 μM) for individual subtypes. The PPAR subtype selectivity of MBX-8025 is evaluated in a cell-based GAL4 reporter assay system[3].

Animal experiment:

Mouse: From weaning (week 4), Alms1 mutant (foz/foz) NOD.B10 mice or Wt littermates (female mice in both groups) are fed an atherogenic diet (23% fat, 0.2% cholesterol and 45% simple carbohydrate; 4.78 kcal/g digestible energy) ad libitum for 16 weeks, after which groups are randomized (n=8 to 12 mice/group) to once-a-day oral administration (by gavage) for 8 weeks of Seladelpar sodium salt (10 mg/kg in 1% methylcellulose) or vehicle (controls). Animals are housed under 12-hour light/dark cycle and constant temperature of 22°C and receive maximal humane care[4].

References:

[1]. Sahebkar A, et al. New peroxisome proliferator-activated receptor agonists: potential treatments for atherogenic dyslipidemia and non-alcoholic fatty liver disease. Expert Opin Pharmacother. 2014 Mar;15(4):493-503.
[2]. Bays HE, et al. MBX-8025, a novel peroxisome proliferator receptor-delta agonist: lipid and other metabolic effects in dyslipidemic overweight patients treated with and without atorvastatin. J Clin Endocrinol Metab. 2011 Sep;96(9):2889-97.
[3]. Choi YJ, et al. Effects of the PPAR-δ agonist MBX-8025 on atherogenic dyslipidemia. Atherosclerosis. 2012 Feb;220(2):470-6.
[4]. Haczeyni F, et al. The selective peroxisome proliferator-activated receptor-delta agonist seladelpar reverses nonalcoholic steatohepatitis pathology by abrogating lipotoxicity in diabetic obese mice. Hepatol Commun. 2017 Jul 31;1(7):663-674.