GSK126

GSK126 (GSK2816126A) is a potent, highly selective inhibitor of EZH2 methyltransferase with an IC₅₀ of 9.9 nM^[1]. IC50 & Target: IC50: 9.9 nM (EZH2)^[1] In Vitro: GSK126 potently inhibits both wild-type and mutant EZH2 methyltransferase activity with similar potencies (K_i=0.5-3 nM) independent of substrate used, and is competitive with S-adenosyl-methionine (SAM) and non-competitive with peptide substrates. GSK126 is highly selective against other methyltransferases and multiple other protein classes (EZH1, IC₅₀=680 nM)^[1]. Treatment of three SCLC cell lines with GSK126, induces growth inhibition. SCLC cell lines (Lu130, H209, and DMS53) are treated with 0.5, 2, and 8 μM GSK126, and growth curve is analyzed by WST-8 assay. Inhibition of cellular growth by GSK126 treatment is observed at 8 μM in all the three cell lines, while Lu130 and H209 are more sensitive to GSK126, even at lower doses^[2]. In Vivo: GSK126 is administered intraperitoneally at a dose volume of 0.2 mL per 20 g body weight in female beige SCID mice. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and markedly inhibits the growth of EZH2 mutant DLBCL xenografts in mice^[1].