GSK126

生物活性体外研究体内研究生物活性靶点体外研究体内研究 GSK126 试剂级价格

GSK126

CAS号:1346574-57-9
英文名:S)-1-(sec-butyl)-N-((4,6-diMethyl-2-oxo-1,2-dihydropyridin-3-yl)Methyl)-3-Methyl-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxaMide
中文名:GSK126
CBNumber:CB72645671
分子式:C31H38N6O2
分子量:526.67
MOL File:1346574-57-9.mol

GSK126化学性质

熔点 :>216°C (dec.)
沸点 :823.4±65.0 °C(Predicted)
密度 :1.25±0.1 g/cm3(Predicted)
储存条件 :-20°C Freezer
溶解度 :DMSO (Slightly), Methanol (Slightly, Heated)
酸度系数(pKa) :11.93±0.10(Predicted)
形态 :Solid
颜色 :Off-White

安全信息

海关编码 :2933998090

GSK126性质、用途与生产工艺

生物活性 GSK126 是一种有效的，高选择性EZH2 methyltransferase抑制剂，IC50为9.9 nM，对 EZH2 的选择性比其他20种人甲基转移酶高1000多倍。
体外研究 GSK126 induced a 50% loss of H3K27 tri-methylation (H3K27me3) in both EZH2 wild-type and mutant DLBCL cell lines at concentrations ranging from 7–252 nM independent of EZH2 mutation status. GSK126 suppresses cell proliferation of a panel of B-cell lymphoma cell lines. Six of the seven most sensitive DLBCL cell lines harboured Y641N, Y641F or A677G EZH2 mutations (growth IC50 = 28–861 nM). 72 h treatment with 500 nM GSK126 induces transcriptional activation in sensitive cell lines.
体内研究 GSK126 treated once-daily for 10 days decreases global H3K27me3 and increases gene expression in subcutaneous xenografts of KARPAS-422 in a dose-dependent fashion. With daily 50 mg per kg dosing, complete tumour growth inhibition is observed. When higher dosing regimens are examined with KARPAS-422 xenografts, marked tumour regression is observed. Upon cessation of dosing, tumours in the 50 mg per kg once daily group shows tumour stasis whereas complete tumour eradication is observed in the 150 mg per kg once daily and 300 mg per kg twice per week groups. Tumour growth inhibition also correlates with statistically significant increased survival of mice bearing the more aggressive KARPAS-422 tumours, where spontaneous deaths occurres in vehicle-treated animals. No significant changes in any blood cell types at doses and times where efficacy is observed in tumour xenografts.
生物活性 GSK126 (GSK2816126A, GSK2816126) 是一种有效的，高选择性EZH2 methyltransferase抑制剂，IC50为9.9 nM，对 EZH2 的选择性比其他20种人甲基转移酶高1000多倍。
靶点
Target Value
EZH2
(Cell-free assay) 9.9 nM
体外研究
在体外，EZH2野生型和突变型DLBCL细胞系中，GSK126最有效地抑制H3K27me3，其次是H3K27me2。GSK126也能有效抑制EZH2突变型DLBCL细胞系的增殖，并诱导敏感细胞系中EZH2靶基因的转录激活。在A687V EZH2突变细胞中，GSK126处理导致总体H3K27me3减少，强基因活化，胱天蛋白酶活化，以及增殖减少。在亲代H2087细胞中，GSK126抑制VEGF-A和磷酸化Ser(473)-AK的表达，因此引起对细胞增殖，迁移和代谢的抑制。
体内研究在负荷KARPAS-422和Pfeiffer异种移植物的小鼠体内，GSK126 (150 mg/kg/d, i.p.)降低总体H3K27me3，增加基因表达，从而引起显著的肿瘤消退。