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GNF-2

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Chemical Structure| 778270-11-4 同义名 : Bcr-Abl Inhibitor
CAS号 : 778270-11-4
货号 : A175756
分子式 : C18H13F3N4O2
纯度 : 98%+
分子量 : 374.317
MDL号 : MFCD09265253
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(280.51 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • Bcr-Abl

    Bcr-Abl (K562 cell line), IC50:273 nM

    Bcr-Abl (SUP-B15 cell line), IC50:268 nM
描述 Bcr-Abl is a 210-kDa fusion protein with the combination of the ABL1 (Abelson tyrosine kinase) and the BCR (breakpoint cluster region) , which is validated as a therapeutic target for the treatment of chronic myelogenous leukemia. GNF-2 is a highly selective non-ATP competitive inhibitor of Bcr-Abl. GNF-2 inhibited cell proliferation with an IC50 of 138 nM and cell growth with an IC50 of ~170 nM in Bcr-Abl-expressing cell lines. The cellular tyrosine phosphorylation of Bcr-Abl was inhibited by GNF-2 in a dose-dependent manner with an IC50 of 267 nM. Treatment of Ba/F3.p210 cell lines with 1 μM GNF-2 for 90min significantly decreased the level of phospho-Stat5. Incubation of 1 μM GNF-2 for 48 hours induced apoptotic death in Ba/F3.p210 (wild type and E255V mutant) cells. With the presence of c-Abl SH3 and/or SH2 domains, 10 μM GNF-2 inhibited tyrosine kinase activity of recombinant Abl in vitro. The phosphorylation of CrkII, a well-characterized c-Abl substrate, was inhibited by GNF-2 in a dose-dependent manner from 0.1 to 10 μM in one hour in c-Abl-reconstituted 3T3 cells. The combination of 5 or 10 μM GNF-2 and 1 μM imatinib decreased the number of resistant clones resulted from continuous exposure to 1 μM imatinib by 90% in Ba/F3 cells after 21-day treatment.
作用机制 GNF-2 inhibits tyrosine kinase activity in c-Abl through competing with the myristoyl residue for binding to the myristate-binding pocket.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.67mL

0.53mL

0.27mL

13.36mL

2.67mL

1.34mL

26.72mL

5.34mL

2.67mL
参考文献

[1]Adrián FJ, Ding Q, Sim T, et al. Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat Chem Biol. 2006;2(2):95-102.

[2]Choi Y, Seeliger MA, Panjarian SB, et al. N-myristoylated c-Abl tyrosine kinase localizes to the endoplasmic reticulum upon binding to an allosteric inhibitor. J Biol Chem. 2009;284(42):29005-14.

[3]Zhang J, Adrián FJ, Jahnke W, et al. Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors. Nature. 2010;463(7280):501-6.