半岛bd体育手机客户端 说明
一般描述
A cell-permeable, metabolically stable (t1/2= 14 h in 786-0 cultures; no metabolization up to 24 h in medium alone), non-cytotoxic (up to 30 ?M & 24 h in 786-0 and Hep3B cultures) benzoxadiazolamine that prevents HIF-2α-HIF-β/ARNT (aryl hydrocarbon receptor nuclear translocator) heterodimeration by perturbing HIF-2α Per-ARNT-Sim/PAS-B domain surface β-sheet conformation via a 1:1 stoichiometric binding to HIF-2α PAS-B internal cavity (KD= 81 nM), while exhibiting no affinity toward HIF-1α PAS-B domain (KD>>5 ?M). Shown to inhibit nuclear HIF-2α-ARNT, but not HIF-1α-ARNT, association in hypoxic Hep3B cells in a dose-dependent manner (0.1 to 10 ?M) and selectively decrease hypoxia-induced HIF-2α DNA binding and HIF-2α-dependentEPOmRNA upregulation (% inhibition/time/dose = 60%/6 h/1 ?M, 90%/6 h/10 ?M, 45%/12 h/1 ?M, 93%/12 h/10 ?M), displaying little effect toward HIF-1α DNA binding or HIF-1α-dependentPGK1mRNA upregulation. Unlike HIF Inhibitors I-VI, this compound does not affect the cellular protein or mRNA levels of HIF-1α & HIF-2α.
A cell-permeable benzoxadiazolamine that prevents HIF-2α-HIF-β/ARNT heterodimeration by perturbing HIF-2α Per-ARNT-Sim/PAS-B domain surface β-sheet conformation via a 1:1 stoichiometric binding (KD= 81 nM), while exhibiting no affinity toward HIF-1αPAS-B domain. Shown to be metabolically stable and non-cytotoxic in cultures and selectively inhibit hypoxia-induced HIF-2α DNA binding and HIF-2α-dependentEPOmRNA upregulation (1 to10 ?M for 6 to 12 h), but not HIF-1α DNA binding or HIF-1α-dependentPGK1mRNA upregulation, in Hep3B cells. Unlike HIF Inhibitors I-VI, this compound does not affect the cellular protein or mRNA levels of HIF-1α & HIF-2α.
生化/生理作用
Cell permeable: yes
Primary Target
HIF-2α
Reversible: yes
包装
Packaged under inert gas
警告
Toxicity: Standard Handling (A)
重悬
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Use only fresh DMSO for reconstitution.
其他说明
Wu, D., et al. 2015.Naturein press.
Scheuermann, T.H., et al. 2013.Nat. Chem. Biol.9,271.
法律信息
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
基本信息
| 经验(实验)分子式 | C12H6ClFN4O3 |
| 分子量 | 308.65 |
半岛bd体育手机客户端 性质
| 测定 | ≥99% (HPLC) |
| 质量水平 | 100 |
| 形式 | powder |
| manufacturer/tradename | Calbiochem? |
| 储存条件 | OK to freeze protect from light |
| 颜色 | yellow |
| 溶解性 | DMSO: 10 mg/mL |
| 储存温度 | 2-8℃ |
安全信息
| 储存分类代码 | 11 - Combustible Solids |
| WGK | WGK 3 |
Sigma-Aldrich
m.cnreagent.com
