ZLD1039 是一种强效、高选择性和口服生物可利用的 EZH2 抑制剂。 ZLD1039 对 PRC2 酶活性对 EZH2 野生型以及 Y641F 和 A677G 突变酶具有有效且浓度依赖性的抑制作用，IC50 值分别为 5.6、15 和 4.0 nM。 ZLD1039 抑制乳腺肿瘤的生长和转移。
货号:ajcx19698
CAS:1826865-46-6
分子式:C36H48N6O3
分子量：612.8
溶解度:Soluble in DMSO
纯度：98%
存储：Store at -20°C
库存：现货

Background:

ZLD1039 is an inhibitor of enhancer of zeste homolog 2 (EZH2; IC50 = 5.6 nM).1 It is selective for EZH2 over EZH1 (IC50 = 81 nM) and is greater than 4,700-fold selective for EZH2 in a panel of 14 histone methyltransferases. ZLD1039 also inhibits mutant Y641F and A677G EZH2 (IC50s = 15 and 4 nM, respectively, in a cell-free enzyme assay). It inhibits methylation of histone 3 lysine 27 (H3K27) in MCF-7 breast cancer cells (IC50 = 0.29 μM) and decreases expression of cadherin-1 (CDH1), cyclin-dependent kinase inhibitor 1C (CDKN1C), CDKN2A, and runt-related transcription factor 3 (RUNX3) in MCF-7 cells when used at concentrations of 1 and 2 μM. It also suppresses migration of MCF-7 cells when used at a concentration of 2 μM. ZLD1039 (200 mg/kg) reduces tumor growth in MCF-7 and MDA-MB-231 mouse xenograft models and inhibits tumor metastasis and decreases tumor protein levels of matrix metalloproteinase-2 (MMP-2), MMP-9, and E-cadherin in a 4T1 mouse xenograft model when administered at a dose of 250 mg/kg.

|1. Song, X., Gao, T., Wang, N., et al. Selective inhibition of EZH2 by ZLD1039 blocks H3K27methylation and leads to potent anti-tumor activity in breast cancer. Sci.Rep. 6:20864, (2016).