5.05052

Ezh2/Ezh1 Inhibitor, UNC1999

• Sinónimos: Ezh2/Ezh1 Inhibitor, UNC1999, Enhancer of Zested Homolog 1 Inhibitor, 1-Isopropyl-6-(6-(4-isopropylpiperazin-1-yl)pyridin-3-yl)-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide, Ezh1 Inhibitor, Ezh2 Inhibitor IV, HMTase Inhibitor XII, Histone Lysi, Enhancer of Zested Homolog 1 Inhibitor, 1-Isopropyl-6-(6-(4-isopropylpiperazin-1-yl)pyridin-3-yl)-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide, Ezh1 Inhibitor, Ezh2 Inhibitor IV, HMTase Inhibitor XII, Histone Lysin
• Fórmula empírica (notación de Hill): C₃₃H₄₃N₇O₂
• Número de CAS: 1431612-23-5
• Peso molecular: 569.74
• Número MDL: MFCD26960958
• Código UNSPSC: 12352200
• ID de la sustancia en PubChem: 72551585
• NACRES: NA.77

Propiedades

• Ensayo: ≥98% (HPLC)
• Nivel de calidad: 100
• Formulario: powder
• fabricante / nombre comercial: Calbiochem^®
• condiciones de almacenamiento: OK to freeze; protect from light
• color: white
• solubilidad: DMSO: 100 mg/mL
• temp. de almacenamiento: 2-8°C
• cadena SMILES: CCCC1=C(C(=O)NC(=C1)C)CNC(=O)C2=C3C=NN(C3=CC(=C2)C4=CN=C(C=C4)N5CCN(CC5)C(C)C)C(C)C

Descripción

Descripción general

A cell-permeable GSK126 structural analog that acts as a potent, SAM-, but not substrate-, competitive inhibitor against Ezh1 and Ezh2 (IC₅₀ = 5, 20, 20, 45 nM against PRC2 complex containing Ezh2 wt, Ezh2 Y641F, Ezh2 Y641N, or wt Ezh1 in H3 peptide methylation assays; [SAM] = 5 µM), while exhibiting much reduced or little potency toward panels of 15 other methyltransferases (IC₅₀ >10 µM), 50 kinases (≤20% inhibition at 10µM), as well as 43 GPCRs, transporters, and ion channels, although high affinity binding is observed with Sigma-2 receptor S2R/PGRMC1 (K_i = 65 nM) with unknown impact toward its function. Cellular H3K27me3 level is shown to be largely reduced in MCF10A, MCF7, and DB cells with no significant effect on proliferation upon a 3-day UNC1999 treatment (IC_max = 3 to 5 µM), while complete cell death is reported in the EZH2 Y641N-harboring DLBCL line DB cell culture upon an 8-day 5 µM drug exposure. Exhibits good bioavailability in mice with the plasma drug concentration maintained above 100 nM for 20 h and 24 h, respectively, following a single 50 mg/kg oral or i.p. dosage (C_max = 4.7 and >9.7 µM, respectively). Both its oral bioavailability and enhanced Ezh1 potency can greatly complement the Ezh2-selective GSK126 in in vitro and in vivo studies.

Acciones bioquímicas o fisiológicas

Cell permeable: yes

Primary Target
Ezh2

Reversible: yes

Secondary Target
Ezh1

Envase

Packaged under inert gas

Advertencia

Toxicity: Standard Handling (A)

Reconstitución

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Otras notas

Konze, K.D., et al. 2013. ACS Chem. Biol.8, 1324.

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