5.05052

Ezh2/Ezh1 Inhibitor, UNC1999

• 동의어(들): 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
• 실험식(Hill 표기법): C₃₃H₄₃N₇O₂
• CAS Number: 1431612-23-5
• Molecular Weight: 569.74
• MDL number: MFCD26960958
• UNSPSC 코드: 12352200
• PubChem Substance ID: 72551585
• NACRES: NA.77

속성

• 분석: ≥98% (HPLC)
• Quality Level: 100
• 양식: powder
• 제조업체/상표: Calbiochem^®
• 저장 조건: OK to freeze; protect from light
• 색상: white
• solubility: DMSO: 100 mg/mL
• 저장 온도: 2-8°C
• SMILES string: 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

설명

일반 설명

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.

생화학적/생리학적 작용

Cell permeable: yes

Primary Target
Ezh2

Reversible: yes

Secondary Target
Ezh1

포장

Packaged under inert gas

경고

Toxicity: Standard Handling (A)

재구성

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

기타 정보

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

법적 정보

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

안전성 정보

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point (°F): Not applicable
• Flash Point (°C): Not applicable