EPZ005687

製品コードS7004 バッチS700401

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C32H37N5O3
分子量 539.67 CAS No. 1396772-26-1
Solubility (25°C)* 体外 DMSO 2 mg/mL (3.7 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 EPZ005687 is a potent and selective inhibitor of EZH2 with Ki of 24 nM in a cell-free assay, 50-fold selectivity against EZH1 and 500-fold selectivity against 15 other protein methyltransferases.
in vitro

EPZ005687 shows concentration-dependent inhibition of PRC2 enzymatic activity with an IC50 value of 54 nM. It is a direct inhibitor of PRC2 enzymatic activity and does not function by disrupting the protein-protein interactions among the PRC2 subunits. EPZ005687 binds in the SAM pocket of the EZH2 SET domain and is a SAM-competitive inhibitor of EZH2 enzyme activity. The affinity of EPZ005687 is similar (within a two-fold range) for PRC2 complexes containing wild-type and Tyr641 mutant EZH2, but significantly greater affinity for the A677G mutant enzyme (5.4-fold). EPZ005687 reduces H3K27 methylation in various lymphoma cells. It shows robust cell killing in heterozygous Tyr641 or Ala677 mutant cells, with minimal effects on the proliferation of wild-type cells. EPZ005687 increases G1 phase of the cell cycle with correlative decreases in the S as well as the G2/M phases. In a Tyr641 mutant lymphoma cell line, EPZ005687 can lead to derepression of known EZH2 target genes and affect genes specifically repressed by the EZH2 Tyr641 mutant. [1]
in vivo

EPZ005687, a selective inhibitor of methyltransferase EZH2, significantly inhibits the development of TAC-induced PAH in an EZH2-SOD1-ROS dependent manner.

プロトコル(参考用のみ)

キナーゼアッセイ Biochemical Enzyme Assays
Compound is incubated for 30 min with 40 μL per well of 5 nM PRC2 (final assay concentration in 50 μL is 4 nM ) in 1X assay buffer (20 mM Bicine [pH 7.6], 0.002% Tween-20, 0.005% Bovine Skin Gelatin and 0.5 mM DTT). 10 μL per well of substrate mix comprising assay buffer 3 H-SAM, unlabeled SAM, and peptide representing histone H3 residues 21-44 containing C-terminal biotin (appended to a C-terminal amide-capped lysine) are added to initiate the reaction (both substrates are present in the final reaction mixture at their respective Km values, an assay format referred to as ‘‘balanced conditions’’. The final concentrations of substrates and methylation state of the substrate peptide are indicated for each enzyme Reactions are incubated for 90 min at room temperature and quenched with 10 μL per well of 600 μM unlabeled SAM, Then transferred to a 384-well flashplate and washed after 30 min.
細胞アッセイ 細胞株 OCI-LY19, WSU-DLCL2, Pfeiffer
濃度 ~10 μM
反応時間 11 days
実験の流れ

Plating densities are determined for each cell line on the basis of linear log-phase growth. Cells are counted and split back to the original plating density in fresh medium with EPZ005687 on days 4 and 7.
動物実験 動物モデル Balb/c mice
投薬量 10 mg/kg
投与方法 i.p.

カスタマーフィードバック

, , Oncogene, 2015, 34(48):5869-78.

, , J Biol Chem, 2017, 292(18):7578-7587

Data from [Data independently produced by , , Nature, 2018, 560(7718):372-376]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

EZH2-H3K27me3-mediated silencing of mir-139-5p inhibits cellular senescence in hepatocellular carcinoma by activating TOP2A [ J Exp Clin Cancer Res, 2023, 42(1):320] PubMed: 38008711
Role of EZH2-mediated H3K27me3 in placental ADAM12-S expression: implications for fetoplacental growth [ BMC Med, 2022, 20(1):189] PubMed: 35610640
Remarkable Synergy When Combining EZH2 Inhibitors with YM155 Is H3K27me3-Independent [ Cancers (Basel), 2022, 15(1)208] PubMed: 36612203
H3.3-K27M drives neural stem cell-specific gliomagenesis in a human iPSC-derived model [ Cancer Cell, 2021, 39(3):407-422.e13] PubMed: 33545065
Targeting EZH2-mediated methylation of histone 3 inhibits proliferation of pediatric acute monocytic leukemia cells in vitro [ Cancer Biol Ther, 2021, 22(4):333-344] PubMed: 33978549
Targeting p53 and histone methyltransferases restores exhausted CD8+ T cells in HCV infection. [ Nat Commun, 2020, 11(1):604] PubMed: 32001678
EZH2-mediated Epigenetic Silencing of miR-29/miR-30 targets LOXL4 and contributes to Tumorigenesis, Metastasis, and Immune Microenvironment Remodeling in Breast Cancer [ Theranostics, 2020, 10(19):8494-8512] PubMed: 32754259
Selective Sensitivity of EZH2 Inhibitors Based on Synthetic Lethality in ARID1A-deficient Gastric Cancer [ Gastric Cancer, 2020, 10.1007/s10120-020-01094-0] PubMed: 32506298
Systematic Analysis of Drug Vulnerabilities Conferred by Tumor Suppressor Loss. [ Cell Rep, 2019, 27(11):3331-3344] PubMed: 31189115
The Attenuation of Trophoblast Invasion Caused by the Downregulation of EZH2 Is Involved in the Pathogenesis of Human Recurrent Miscarriage [ Mol Ther Nucleic Acids, 2019, 14:377-387] PubMed: 30710891

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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