BioE-1115

BioE-1115 is a selective and potent inhibitor of serine-threonine protein kinase (PASK, IC50 = 4 nM) . BioE-1115 is a potent inhibitor of CK2α (IC50 = 10 μM) . (In Vitro) :In HepG2 cells, BioE-1115 (>10μM) treatment shows a significant reduction in SREBP activity, without any observable effects on cell morphology or growth rate. In HEK293 cells, BioE-1115 shows a dose-dependent loss of PASK phosphorylation (IC50 =1μM) . (In Vivo) :In male Sprague-Dawley rats, BioE-1115 (10, 30 and 100 mg/kg) treatment shows a dose-dependent suppression of the expression of Gpat1, Fasn, and all other SREBP-1c target genes analyzed. SREBP-1 maturation in the liver is also suppressed in BioE-1115 treated rats. A calculated measure of insulin resistance, HOMA-IR, is decreased in a dose-dependent manner by BioE-1115 administration. Hepatic and serum TAG are decreased in a dose-dependent manner by BioE-1115 administration. BioE-1115 treatment causes a significant decrease in serum glucose. Both SREBP-1c and SREBP-1a mRNA are modestly decreased at the highest doses. Neither dose of BioE-1115 causes a significant change in either liver weight or body weight.