252790

DZNep

≥97% (HPLC), solid, EZH2 inhibitor, Calbiochem^®

• Sinónimos: Histone Methyltransferase EZH2 Inhibitor, DZNep, 3-deazaneplanocin A, HCl; (1S,2R,5R)-5-(4-amino-1H-imidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)cyclopent-3-ene-1,2-diol, HCl, HMTase Inhibitor X
• Fórmula empírica (notación de Hill): C₁₂H₁₄N₄O₃ · xHCl · yH₂O
• Número de CAS: 120964-45-6
• Peso molecular: 262.26 (anhydrous free base basis)
• Número MDL: MFCD18782644
• Código UNSPSC: 12352200
• NACRES: NA.77

Propiedades

• product name: Histone Methyltransferase EZH2 Inhibitor, DZNep, Histone Methyltransferase EZH2 Inhibitor, DZNep, CAS 120964-45-6, is a cell-permeable inhibitor of EZH2-mediated trimethylation of K27 on histone H3.
• Nivel de calidad: 100
• Análisis: ≥97% (HPLC)
• formulario: solid
• fabricante / nombre comercial: Calbiochem^®
• condiciones de almacenamiento: OK to freeze; desiccated (hygroscopic); protect from light
• color: tan
• solubilidad: DMSO: 10 mg/mL
• Condiciones de envío: wet ice
• temp. de almacenamiento: −20°C
• InChI: 1S/C12H14N4O3.ClH/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);1H/t8-,10-,11+;/m1./s1
• Clave InChI: UNSKMHKAFPRFTI-FDKLLANESA-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.

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. Also available as a 25 mM solution in H₂O (Cat. No. 506069).

Envase

Packaged under inert gas

Advertencia

Toxicity: Standard Handling (A)

Forma física

Supplied as a hydrochloride salt.

Reconstitución

Following reconstitution, aliquot and freeze 9-20°C). Stock solutions are stable for up to 3 months at -20°C.

Otras notas

Fiscus, W., et al. 2009. Blood13, 2733.

Información legal

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

Información de seguridad

• Código de clase de almacenamiento: 11 - Combustible Solids
• Clase de riesgo para el agua (WGK): WGK 3
• Punto de inflamabilidad (°F): Not applicable
• Punto de inflamabilidad (°C): Not applicable