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UNC1999

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Chemical Structure| 1431612-23-5 同义名 : -
CAS号 : 1431612-23-5
货号 : A108081
分子式 : C33H43N7O2
纯度 : 99%+
分子量 : 569.74
MDL号 : MFCD26960958
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(184.29 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 8 mg/mL clear

PO 0.5% CMC-Na 20 mg/mL suspension

生物活性
靶点

  • Histone Methyltransferase

    EZH2, IC50:2 nM

    EZH1, IC50:45 nM
描述 EZH2 or EZH1 is the catalytic subunit of the polycomb repressive complex 2 that catalyzes methylation of histone H3 lysine 27 (H3K27), which cause the gene expression silence. UNC1999 is a dual inhibitor of EZH2 and EZH1 with IC50 values of 2 nM and 45 nM (measured by PRC2 enzymatic activity)，respectively, and is over 1000-fold selective for other HMTs[1]. UNC1999 (72h exposure) exhibited dose-dependent reductions in H3K27me3 with an IC50 value of 124 ± 11 nM in MCF10A cells bearing the WT EZH2 enzyme. The treatment of MCF7 cells with UNC1999 at 5,000 nM for 72 h almost completely removed the H3K27me3 mark but did not have significant effects on cellular levels of EZH2. UNC1999 selectively killed EZH2-mutant DLBCL cells with heterozygous for Y641 point mutations. Exposure of UNC1999 for 8 days displayed dose-dependent inhibition of cell proliferation with an EC50 of 633 ± 101 nM in DB cells, while 5,000 nM UNC1999 can completely killed DB cells. UNC1999 may be a good probe for EZH2 for biotinylated UNC1999 can be used to pull down EZH2 from cell lysates and UNC1999–dye conjugate co-localizes with EZH2 in live cells[2]. Oral administration of UNC1999 (50 mg/kg, twice daily) starting from 7 days post-transplantation prolongs survival of a well-defined murine leukemia model bearing MLL-AF9, with significantly decreased H3K27me3 and elevated their p16Ink4a or p19Arf expression in cells isolated from bone marrow and spleen[3].
作用机制 UNC1999 is a SAM-competitive inhibitor of EZH2 and EZH1[2].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human MCF10A cells Function assay 72 h Inhibition of EZH2 in human MCF10A cells assessed as reduction of H3K27me3 level after 72 hrs by Western blot analysis, IC50=0.124 μM 25406853
human MCF10A cells Cytotoxic assay Cytotoxicity against human MCF10A cells assessed as cell viability by Alamar Blue assay, EC50=19.2 μM 25406853
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.76mL

0.35mL

0.18mL

8.78mL

1.76mL

0.88mL

17.55mL

3.51mL

1.76mL
参考文献

[1]UNC1999 A chemical probe for EZH2/1

[2]Konze KD, Ma A, et al. An orally bioavailable chemical probe of the Lysine Methyltransferases EZH2 and EZH1. ACS Chem Biol. 2013;8(6):1324-34.

[3]Xu B, On DM, et al. Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia. Blood. 2015 Jan 8;125(2):346-57.

[4]Inhibitors of Protein Methyltransferases and Demethylases