受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C32H37N5O3 |
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分子量 | 539.67 | CAS No. | 1396772-26-1 | ||||||||
Solubility (25°C)* | 体外 | DMSO | 27 mg/mL (50.03 mM) | ||||||||
Water | Insoluble | ||||||||||
Ethanol | Insoluble | ||||||||||
体内 (毎回新しく調製した物を用意してください) |
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* <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. |
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. |
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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. |
キナーゼアッセイ | Biochemical Enzyme Assays | |
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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. |
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動物実験 | 動物モデル | Balb/c mice |
投薬量 | 10 mg/kg | |
投与方法 | i.p. |
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, , 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]
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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