5.00561

Ezh2 Inhibitor II, EI1

• 別名: Ezh2 Inhibitor II, EI1, Enhancer of Zested Homolog 2 Inhibitor II, HMTase Inhibitor XI, 6-Cyano-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-(pentan-3-yl)-1H-indole-4-carboxamide
• 実験式（ヒル表記法）: C₂₃H₂₆N₄O₂
• CAS番号: 1418308-27-6
• 分子量: 390.48
• MDL番号: MFCD25976740
• UNSPSCコード: 12352200
• NACRES: NA.77

特性

• アッセイ: ≥98% (HPLC)
• 品質水準: 100
• フォーム: solid
• メーカー／製品名: Calbiochem^®
• 保管条件: OK to freeze; protect from light
• 色: white
• 溶解性: DMSO: 10 mg/mL
• 保管温度: 2-8°C
• SMILES記法: [nH]1[c](c(c(cc1C)C)CNC(=O)c2c3c([n](cc3)C(CC)CC)cc(c2)C#N)=O
• InChI: 1S/C23H26N4O2/c1-5-17(6-2)27-8-7-18-19(10-16(12-24)11-21(18)27)22(28)25-13-20-14(3)9-15(4)26-23(20)29/h7-11,17H,5-6,13H2,1-4H3,(H,25,28)(H,26,29)
• InChI Key: PFHDWRIVDDIFRP-UHFFFAOYSA-N

詳細

詳細

A cell-permeable indolocarboxamide compound that acts as a potent and selective inhibitor against Ezh2/PRC2 (Polycomb repressive complex 2; Ezh2/SUZ12/EED/AEBP2/RbAP48) HMTase activity (IC₅₀/substrate = 15 nM/H3K27me0_21-44 and 13 nM/H3K27me2_21-44, respectively, against human wt or Y641F Ezh2-containing PRC2; [SAM] = 1 µM) in a cofactor SAM-competitive manner, while inhibiting Ezh1/PRC2 only at much higher concentrations (IC₅₀ = 1.34 µM) and exhibiting no potency toward CARM 1, Dot1L, G9a, MLL, NSD3, Set7/9, SETD2, SETD8, SmyD2, or Suv39H2 (IC₅₀ >100 µM). Shown to selectively suppress cellular H3K27 dimethylation and trimethylation (1 to 10 µM in 1 to 5 days) in DLBCL (diffuse large B cell lymphoma) cultures, but not those of H3K4, H3K9, H3K36, or H3K79. EI1 is shown to exhibit antiproliferation activity against DLBCL cell lines with wt- (by 90% in G401 with 3.3 µM EI1; by 78% in Toledo with 10 µM EI1; 14 d incubation) or mutant- Ezh2 (by &gt96% in WSU-DLCL2/Y641F, SU-DHL6/Y641N, Karpas422/Y641N, and DB/Y641N cultures with 3.3 µM EI1; by &gt96% in SU-DHL4 cultures with10 µM EI1; 14 d incubation), while being less effective against MEF (by 40% in 11 days at 3.3 µM) and ineffective toward wt Ezh2-expressing GA10 and OCI-LY19.

生物化学的／生理学的作用

Cell permeable: yes

Primary Target
Ezh2/PRC2

Reversible: yes

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

再構成

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

その他情報

Qi, W., et al. 2012. Proc. Natl. Acad. Sci. USA.109, 21360.

法的情報

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

安全性情報

• 保管分類コード: 11 - Combustible Solids
• WGK: WGK 2