Biological Activity of LY2090314

LY2090314  is a potent inhibitor of glycogen synthase kinase-3 (GSK-3) with IC50s of 1.5 nM and 0.9 nM for GSK-3α and GSK-3β respectively.
IC50 Value: 1.5 nM (GSK-3α); 0.9 nM (GSK-3β) [1]
Target: GSK-3α; GSK-3β
LY2090314  is a potent inhibitor of glycogen synthase kinase-3 (GSK-3) which plays an important role in many pathways, including initiation of protein synthesis, cell proliferation, cell differentiation, and apoptosis.
in vitro: LY2090314 selectively inhibits the activity of GSK-3 by interrupting ATP binding. LY2090314 is able to stabilize β-catenin. LY2090314 shows limited efficacy as monotherapy. LY3090314 enhances the efficacy of cisplatin and carboplatin in solid tumor cancer cell lines in vitro.
in vivo: Even in Mdr1a-, Bcrp-, and Mrp2-knockout rats, LY2090314 metabolites did not appear in circulation, and their urinary excretion was not enhanced, because the hypothesized impaired biliary excretion of metabolites in the absence of these canalicular transporters was not observed. Canine metabolite disposition was generally similar, with the notable exception of dog-unique LY2090314 glucuronide [1].
Toxicity:
Clinical trial: A Study of LY-2090314 and Chemotherapy in Participants With Metastatic Pancreatic Cancer. Phase1/2
 

Clinical Information of LY2090314

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References on LY2090314

[1]. Zamek-Gliszczynski MJ, et al. Pharmacokinetics, metabolism, and excretion of the glycogen synthase kinase-3 inhibitor LY2090314 in rats, dogs, and humans: a case study in rapid clearance by extensive metabolism with low circulating metabolite exposure. Drug Metab Dispos. 2013 Apr;41(4):714-26.