LY2090314 | Wnt/ß-Catenin pathway activator/GSK-3 inhibitor

Wnt/ß-catenin pathway activator. LY2090314 (603288-22-8) is a highly potent (IC₅₀ = 1.5 nM GSK-3α; 0.9 nM GSK-3ß) and selective inhibitor of glycogen synthase-3-kinase (GSK-3).^1,2  It stabilized ß-catenin levels and elevated expression of Axin2 leading to tumor growth delays in A375 melanoma xenografts.2 LY2090314 significantly reduced growth in multiple neuroblastoma cell lines.³ It inhibited growth and induced apoptosis in osimertinib-resistant lung cancer cells, specifically those with a mesenchymal phenotype.⁴

References/Citations:

1. Engler et al. (2004), Substituted 3-imidazo[1,2-a]pyridine-3-yl-4-(1,2,3,4-tetrahydro-[1,4]diazepino-[6,7,1=hi]indol-7-yl)pyrrole-2,5-diones as and potent inhibitors of glycogen synthase-3-kinase; J. Med. Chem. 47 3934
2. Atkinson et al. (2015), Activating the Wnt/ß-Catenin Pathway for the Treatment of Melanoma – Application of LY2090314, a Novel Selective Inhibitor of Glycogen Synthase Kinase-3; PLoS One 10 e0125028
3. Kunnimalaiyaan et al. (2018), Antiproliferative and apoptotic effect of LY2090314, a GSK-3 inhibitor, in neuroblastoma in vitro BMC Cancer 18 560
4. Fukuda et al. (2020), Glycogen synthase kinase-3 inhibition overcomes epithelial-mesenchymal transition-associated resistance to Osimertinib in EGFR-mutant lung cancer; Cancer Sci. 111 2374