1431612-23-5|UNC1999|CsnPharm

CAS No.: 1431612-23-5

UNC1999 Catalog No. CSN17166

UNC1999 is a potent, orally bioavailable and selective inhibitor of EZH2 and EZH1 with IC50 of 2 nM and 45 nM, respectively.

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400-920-2911

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纯度 & 质量文件批次:

靶点选择性

生物活性

实验方案

技术信息

生物活性

靶点 EZH1

IC50:45nM EZH2

IC50:2nM
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

Cell Data

Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
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

动物研究

剂量

Mice: min = 15 mg/kg, max = 150 mg/kg^[2] (i.p.); 50 mg/kg^[4] (p.o.)

给药途径

i.p., p.o.

动物药代数据

Animal	Mice^[2]
Dose	15 mg/kg 50 mg/kg
Administration	i.p. p.o.
C_max	9700 nM (i.p.) 4700 nM (p.o.)

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

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 1.7552 mL
- 8.7759 mL
- 17.5519 mL
- 5 mM
- 0.3510 mL
- 1.7552 mL
- 3.5104 mL
- 10 mM
- 0.1755 mL
- 0.8776 mL
- 1.7552 mL

技术信息

CAS号

1431612-23-5

储存条件

粉末: Sealed in dry,2-8°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C33H43N7O2

运输

蓝冰

分子量

569.74

别名

溶解度

DMSO	300.0 mg/mL (526.6 mM) warming
Water	insoluble

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

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UNC1999 Catalog No. CSN17166

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