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EPZ005687 (Synonyms: EPZ 005687,EPZ-005687)

カタログ番号GC13878

EZH2の強力で選択的な阻害剤

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EPZ005687 化学構造

Cas No.: 1396772-26-1

サイズ 価格 在庫数 個数
5mg
$46.00
在庫あり
25mg
$155.00
在庫あり

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Kinase experiment [1]:

Biochemical enzyme assays

Compound was incubated for 30 mins with 40 μL per well of 5 nM PRC2 (final assay concentration in 50 μL was 4 nM) in 1× 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 3H-SAM, unlabeled SAM, and peptide representing histone H3 residues 21-44 containing C-terminal biotin (appended to a C-terminal amide-capped lysine) were added to initiate the reaction (both substrates were 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 were indicated for each enzyme. Reactions were incubated for 90 mins at room temperature and quenched with 10 μL per well of 600 μM unlabeled SAM. The mixtures were then transferred to a 384-well flashplate and washed after 30 mins.

Cell experiment [1]:

Cell lines

OCI-LY19, WSU-DLCL2 and Pfeiffer cells

Preparation method

The solubility of this compound in DMSO is limited. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months.

Reaction Conditions

0.011 ~ 8.3 μM; 11 days

Applications

EPZ005687 significantly inhibited the proliferation of WSU-DLCL2 and Pfeiffer cells, with minimal effects on the proliferation of OCI-LY19 cells.

Animal experiment [2]:

Animal models

Osteoarthritis (OA) mouse model

Dosage form

5.6 μM, 50 μL; intra-articular injection; at 7th, 15th and 30th days

Applications

Intra-articular injection of EPZ005687 delayed OA development in mice.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Knutson SK, Wigle TJ, Warholic NM, Sneeringer CJ, Allain CJ, Klaus CR, Sacks JD, Raimondi A, Majer CR, Song J, Scott MP, Jin L, Smith JJ, Olhava EJ, Chesworth R, Moyer MP, Richon VM, Copeland RA, Keilhack H, Pollock RM, Kuntz KW. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol. 2012 Nov;8(11):890-6.

[2]. Chen L, Wu Y, Wu Y, Wang Y, Sun L, Li F. The inhibition of EZH2 ameliorates osteoarthritis development through the Wnt/β-catenin pathway. Sci Rep. 2016 Aug 19;6:29176.

Background

EPZ005687は、ヒストンH3のリシン27(H3K27)のメチル化を触媒するポリコーム抑制複合体2(PRC2)の酵素サブユニットであるEZH2の強力な阻害剤であり、EZH2を24 nM以下の阻害定数Kiで阻害し、15種類の他のタンパク質メチルトランスフェラーゼと関連性が高いEZH1よりも500倍から50倍以上選択性が高くなっています。EPZ005687は、EZHZ SETドメインのS-アデノシルメチオニン(SAM)ポケットに結合することにより、濃度依存的にPRC2酵素活性を54 nM以下のIC50値で阻害します。研究結果は、EPZ005687がさまざまなリンパ腫細胞中でH3K27メチル化を減少させ、半数致死濃度(IC50)54nM において異型Tyr641またはAla677変異細胞内でアポトーシス誘導作用を示すことを示しています。

参考文献

[1].Knutson SK、Wigle TJ、Warholic NM、Sneeringer CJ、Allain CJ、Klaus CR、Sacks JD、Raimondi A、Majer CR、Song J、Scott MP Jin L, Smith JJ, Olhava EJ, Chesworth R, Moyer MP, Richon VM, Copeland RA, Keilhack H, Pollock RM and Kuntz KW. EZH2の選択的阻害剤はH3K27メチル化をブロックし変異リンパ腫細胞を殺します。Nat Chem Biol. 2012年11月;8(11):890-6。

Chemical Properties

Cas No. 1396772-26-1 SDF
同義語 EPZ 005687,EPZ-005687
Chemical Name 1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[4-(morpholin-4-ylmethyl)phenyl]indazole-4-carboxamide
Canonical SMILES CC1=CC(=C(C(=O)N1)CNC(=O)C2=C3C=NN(C3=CC(=C2)C4=CC=C(C=C4)CN5CCOCC5)C6CCCC6)C
Formula C32H37N5O3 M.Wt 539.67
溶解度 ≥ 3.86 mg/mL in DMSO, <2.29 mg/mL in EtOH, <2.37 mg/mL in Water Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 1.853 mL 9.2649 mL 18.5298 mL
5 mM 0.3706 mL 1.853 mL 3.706 mL
10 mM 0.1853 mL 0.9265 mL 1.853 mL
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計算

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Average Rating: 5 ★★★★★ (Based on Reviews and 30 reference(s) in Google Scholar.)

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