GSK343

GSK343 is a highly potent and selective EZH2 inhibitor with an IC₅₀ of 4 nM. IC50 & Target: IC50: 4 nM (EZH2), 240 nM (EZH1)^[1] In Vitro: GSK343, which contains an n-propyl group at the 4-position of the pyridone, has EZH2 K_i^app=1.2±0.2 nM. In this 6-day proliferation assay, among the cell lines evaluated in this study, the prostate cancer cell line LNCaP is the most sensitive to EZH2 inhibition, with growth IC₅₀ value of 2.9 μM for GSK343^[1]. GSK343 is found to have half maximal inhibitory concentration values of 13 μM in HeLa cells and 15 μM in SiHa cells^[2]. In Vivo: Compare with the controls, GSK343 (5 mg/kg)-treated mice exhibits significantly inhibited tumor growth. The average tumor volume and weight of the GSK343-treated cohort is remarkably reduced. As early as 20 days post-implantation, a significant reduction in tumor growth is observed in the GSK343-treated cohort relative to the control cohort; this difference persisted through the remainder of the study. In addition, compare with the control cohort, the GSK343-treated animals in the xenograft model show a remarkable increase in messenger RNA levels of E-cadherin but a significant decrease in vimentin messenger RNA levels^[2].