5.06069

3-Deazaneplanocin A hydrochloride

InSolution, ≥98%, 25 mM aqueous solution, EZH2 Inhibitor

• 別名: InSolution EZH2 Inhibitor, DZNep, 3-Deazaneplanocin A, xHCl, yH₂O {x = 3 & y = 2}, (1S,2R,5R)-5-(4-Amino-1H-imidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)cyclopent-3-ene-1,2-diol, xHCl, yH₂O {x = 3 & y = 2}, NSC 617989
• 実験式（ヒル表記法）: C₁₂H₁₄N₄O₃ · 3HCl · 2H₂O
• CAS番号: 102052-95-9
• 分子量: 407.68
• UNSPSCコード: 12352200
• NACRES: NA.77

特性

• 品質水準: 100
• アッセイ: ≥98% (HPLC)
• 形状: liquid
• メーカー／製品名: Calbiochem^®
• 保管条件: OK to freeze; avoid repeated freeze/thaw cycles; protect from light
• 保管温度: −70°C
• InChI: 1S/C12H14N4O3/c13-12-9-7(1-2-14-12)16(5-15-9)8-3-6(4-17)10(18)11(8)19/h1-3,5,8,10-11,17-19H,4H2,(H2,13,14)/t8-,10-,11+/m1/s1
• InChI Key: OMKHWTRUYNAGFG-IEBDPFPHSA-N

詳細

詳細

A cell-permeable compound that is shown (at 1 µM concentrations) to inhibit EZH2-mediated trimethylation of K27 on histone H3 and induces the expression of cell-cycle regulatory genes, p21 and p27, as well as the cell death regulator, FBXO32, in OCI-AML3 and HL-60 cells, whereby treatment with inhibitor increases p16 levels in the former, but not the latter of the two cultures. At concentrations between 200 nm and 2000 nM, this compound is found to dose-dependently deplete the expression of polycomb group proteins EZH2, SUZ12, and EED in cultured and primary AML cell extracts. At concentrations up to ≥ 1000 nM, DZNep dose-dependently increases the percentage of apoptotic cells up to > ~ 38%, with greater potency against OCI-AML3 than HL-60 cultures and inhibits colony growth up to > ~ 85% for both cell lines. In OCI-AML3 cultures, 1000 nM of treatment demonstrates a significant increase in the accumulation of cells in the G₀/G₁ phase (58.5%) with a concomitant decrease in the number of cells in S phase (35.2%) and G₂/M phases (6.3%) of the cell cycle. When co-treated with panobinostat (PS), 200 nM to 1000nM DZNep is shown to decrease cell viability in OCI-AML3 and HL-60 cultures more effectively than DZNep alone, in a dose-dependent manner. DZNep (1mg/kg, twice per week, i.p.) and PS significantly prolong the survival of mice implanted with HL-60 cells compared to treatment with either compound alone. DZNep is also a known S-adenosyl-L-homocysteine (AdoHcy) hydrolase inhibitor.

生物化学的／生理学的作用

Cell permeable: yes

Primary Target
EZH2

Reversible: yes

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

物理的形状

A 25 mM (1 mg/98 µL) sterile-filtered solution of Histone Methyltransferase EZH2 Inhibitor, DZNep (Cat. No. 252790) in H₂O.

再構成

Following initial thaw, aliquot and freeze (-20°C). Aliquots are stable for up to 6 monthst at -20°C.

その他情報

Sun, F., et al. 2009. Mol. Cancer Ther.8, 3191.
Miranda, T.B., et al. 2009. Mol. Cancer Ther.8, 1579.
Fiscus, W., et al. 2009. Blood13, 2733.
Tan, J., et al. 2007. Genes Dev.21, 1050.
Chiang, P.K., et al. 1992. J. Biol. Chem.267, 4988.
Tseng, C.K., et al. 1989. J. Med. Chem.32, 1442.
Glazer, R.I., et al. 1986. Biochem. Biophys. Res. Commun.135, 688.

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: 12 - Non Combustible Liquids
• WGK: WGK 2
• 引火点(°F): Not applicable
• 引火点(℃): Not applicable