Tazemetostat hydrobromide (EPZ-6438 hydrobromide) 是一种有效，选择性，口服的 EZH2 抑制剂。Tazemetostat hydrobromide 抑制含有 PRC2 复合体的野生型 EZH2 的活性， Ki 值为 2.5±0.5 nM。Tazemetostat hydrobromide 抑制 EZH2，在肽测定和核小体测定中 IC50 分别为 11 和 16 nM。Tazemetostat hydrobromide 抑制大鼠 EZH2，IC50 为 4
Tazemetostat hydrobromide (EPZ-6438 hydrobromide) is a potent, selective and orally available EZH2 inhibitor. Tazemetostat hydrobromide inhibits the activity of human polycomb repressive complex 2 (PRC2)-containing wild-type EZH2 with a Ki value of 2.5 nM. Tazemetostat hydrobromide inhibits EZH2 with IC50s of 11 and 16 nM in peptide assay and nucleosome assay, respectively. Tazemetostat hydrobromide inhibits Rat EZH2 with an IC50 of 4 nM. Tazemetostat hydrobromide also inhibits EZH1 with an IC50 of 392 nM.
Tazemetostat (EPZ-6438) inhibits multi wild-type and mutant lymphoma cell lines proliferation with IC50s of 0.49 nM-7.6 μM[1]. Cell Proliferation Assay[1] Cell Line: Wild-type and mutant lymphoma cell lines: DOHH-2 cell (EZH2 wild-type), Farage cell (EZH2 wild-type), OCI-LY19 cell (EZH2 wild-type), Toledo cell (EZH2 wild-type), KARPAS-422 (EZH2 Y646N), Pfeiffer (EZH2 A682G), RL cell line (EZH2 Y646N), SU-DHL-10 (EZH2 Y646F), SU-DHL-6 (EZH2 Y646N), WSU-DLCL2 (EZH2 Y646F)
Tazemetostat (EPZ-6438; 250 or 500 mg/kg twice daily for 21-28 days) practically eliminates the fast-growing G401 tumors[1]. Animal Model: SCID mice bearing s.c. G401 xenografts [1]
[1]. Knutson SK, et al. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferaseEZH2. Proc Natl Acad Sci U S A. 2013 May 7;110(19):7922-7.
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