5.06069

3-Deazaneplanocin A hydrochloride

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

• Sinónimos: 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
• Fórmula empírica (notación de Hill): C₁₂H₁₄N₄O₃ · 3HCl · 2H₂O
• Número de CAS: 102052-95-9
• Peso molecular: 407.68
• Código UNSPSC: 12352200
• NACRES: NA.77

Propiedades

• Nivel de calidad: 100
• Análisis: ≥98% (HPLC)
• formulario: liquid
• fabricante / nombre comercial: Calbiochem^®
• condiciones de almacenamiento: OK to freeze; avoid repeated freeze/thaw cycles; protect from light
• temp. de almacenamiento: −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
• Clave InChI: OMKHWTRUYNAGFG-IEBDPFPHSA-N

Descripción

Descripción general

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.

Acciones bioquímicas o fisiológicas

Cell permeable: yes

Primary Target
EZH2

Reversible: yes

Envase

Packaged under inert gas

Advertencia

Toxicity: Standard Handling (A)

Forma física

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

Nota de preparación

This product is a 25 mM (1 mg/98 µL) sterile-filtered solution in H₂O.

Reconstitución

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

Otras notas

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.

Información legal

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

Información de seguridad

• Código de clase de almacenamiento: 12 - Non Combustible Liquids
• Clase de riesgo para el agua (WGK): WGK 2
• Punto de inflamabilidad (°F): Not applicable
• Punto de inflamabilidad (°C): Not applicable