GSK126

• CAT Number: I001332
• CAS Number: 1346574-57-9
• Molecular Formula: C₃₁H₃₈N₆O₂
• Molecular Weight: 526.67
• Purity: ≥95%
• Synonyms: 1-[(2S)-butan-2-yl]-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-methyl-6-(6-piperazin-1-ylpyridin-3-yl)indole-4-carboxamide
• Target: EZH2
• Solubility: 50 mM in DMSO
• Storage: Store at -20°C
• IC50: 0.5 nM (Ki)
• InChI: InChI=1S/C31H38N6O2/c1-6-22(5)37-18-20(3)29-25(30(38)34-17-26-19(2)13-21(4)35-31(26)39)14-24(15-27(29)37)23-7-8-28(33-16-23)36-11-9-32-10-12-36/h7-8,13-16,18,22,32H,6,9-12,17H2,1-5H3,(H,34,38)(H,35,39)/t22-/m0/s1
• InChIKey: FKSFKBQGSFSOSM-QFIPXVFZSA-N
• SMILES: CCC(C)N1C=C(C2=C(C=C(C=C21)C3=CN=C(C=C3)N4CCNCC4)C(=O)NCC5=C(C=C(NC5=O)C)C)C

GSK126(cas 1346574-57-9) is a potent, highly selective, S-adenosyl-methionine-competitive, small-molecule inhibitor of EZH2 methyltransferase with Ki value of 0.5 nM.

in vitro: Although GSK126 induced loss of H3K27me3 independent of EZH2 mutation status, six of seven lymphoma cell lines sensitive to GSK126 treatment were EZH2-mutation(+), while only two of 11 lymphoma cell lines less sensitive to GSK126 were EZH2-mutation(+). SCLC cell lines were then treated with a selective EZH2 inhibitor, GSK126, at different doses of 0.5, 2, and 8 μM.
in vivo: GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and markedly inhibits the growth of EZH2 mutant DLBCL xenografts in mice.

Reference

1:Blocking EZH2 methylation transferase activity by GSK126 decreases stem cell-like myeloma cells. Zeng D, Liu M, Pan J.Oncotarget. 2017 Jan 10;8(2):3396-3411. doi: 10.18632/oncotarget.13773. PMID: 27926488 Free PMC Article
2:[Effect of a novel EZH2 inhibitor GSK126 on prostate cancer cells]. Lin W, Chen Y, Zeng L, Ying R, Zhu F.Zhejiang Da Xue Xue Bao Yi Xue Ban. 2016 May 25;45(4):356-363. Chinese. PMID: 27868408
3:The novel EZH2 inhibitor, GSK126, suppresses cell migration and angiogenesis via down-regulating VEGF-A. Chen YT, Zhu F, Lin WR, Ying RB, Yang YP, Zeng LH.Cancer Chemother Pharmacol. 2016 Apr;77(4):757-65. doi: 10.1007/s00280-016-2990-1. Epub 2016 Feb 22. PMID: 26898301