GSK126

Background Information:

GSK126 is a cell permeable highly potent and selective small molecule
inhibitor of histone methyltransferase EZH2, inhibiting potently both
wild-type and mutant EZH2 methyltransferase activity with similar
potencies (Kiapp =0.5–3 nM), independent of substrate used, and is
competitive with S-adenosylmethionine (SAM) and noncompetitive with
peptide substrates. It is 150-fold more selective for the closest EZH1
(Kiapp 89 nM) and more than 1,000-fold selective over 20 other human
methyltransferases, and multiple other protein classes, including both
SET-domain-containing and non-SET domain-containing methyltransferases.
It induced a 50% loss of H3K27me3 in both EZH2 wild type and mutant
DLBCL cell lines at nM concentrations independent of EZH2 mutation
status. GSK126 can decrease global H3K27me3 levels and reactivate
silenced PRC2 target genes. It effectively inhibits the proliferation of
EZH2 mutant DLBCL cell lines, and markedly inhibits the growth of EZH2
mutant DLBCL xenografts in mice.

Reference:

1. M. T. McCabe, et al, EZH2 inhibition as a therapeutic strategy for
lymphoma with EZH2-activatingmutations. Nature. 2012 Dec 6;
492(7427):108-12.

APIM050329: GSK126

CAS No.: 1346574-57-9.
Molecular Formula: C₃₁H₃₈N₆O₂ ? HCl ? H₂O.
Molecular Weight: 581.2.
Purity: 100% optical purity (Chiral HPLC), 99.5% (HPLC at 214 and 254 nm).
QC: HPLC-MS, NMR, Chiral HPLC and Quantitative Elemental Analysis.
Solubility: Soluble in DMSO.
Storage: Store at 0°C (short term), -20°C (long term), desiccated.