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GNF-5

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Chemical Structure| 778277-15-9 同义名 : -
CAS号 : 778277-15-9
货号 : A117001
分子式 : C20H17F3N4O3
纯度 : 98%
分子量 : 418.369
MDL号 : MFCD16877246
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(119.51 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：

IP 2% DMSO+2% Tween80+30% PEG300+water 8 mg/mL clear

PO 0.5% CMC-Na 36 mg/mL suspension

生物活性
靶点

  • Bcr-Abl

    Bcr-Abl, IC50:220 nM
描述 Bcr-Abl fusion protein is formed as a result of a chromosomal translocation event forming the Philadelphia chromosome that fuses the breakpoint cluster region (BCR) gene to the N-terminus of the Abelson tyrosine kinase (ABL1) gene, which cause Chronic myelogenous leukemia(CML)[3]. GNF-5 is a highly selective non-ATP competitive inhibitor of Bcr-Abl with IC50 value of 0.22μM. GNF-5 alters conformation and hydrogen exchange in the peptide near the ATP-site. In vitro, GNF-5 exhibited inhibition of wild-type Bcr-Abl transformed Ba/F3 cells. Treatment with 10μM GNF-5 significantly inhibited the proliferation of T315I Bcr-Abl Ba/f3 cells[1]. Treatment MDA-MB-231 cells with 10μM GNF-5 decreased in active, matrix-degrading invadopodia, but did not affect cell proliferation. In addition, GNF-5 affected cortactin tyrosine phosphorylation and reduced actin barbed end generation in MDA-MB-231 cells[4]. In vivo, oral administered GNF-5 at 75mg/kg twice daily significantly extended survival of the mice transplanted with T315I Bcr-Abl transduced bone marrow[1].Treatment MDA-MB-231 cells xenograft mouse model with GNF-5 at dose of 100mg/kg once daily via oral gavage for 4 weeks suppressed matrix metalloproteinase (MMP) activity, tumor cell invasion, and consequent spontaneous metastasis to lungs[4].
作用机制 GNF-5 binds to the myristate pocket near the C-terminus of the ABL kinase domain and transmits structural changes to the ATP binding site[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.39mL

0.48mL

0.24mL

11.95mL

2.39mL

1.20mL

23.90mL

4.78mL

2.39mL
参考文献

[1]Zhang J, Adrian F, Jahnke W, et al. Targeting Bcr–Abl by combining allosteric with ATP-binding-site inhibitors. Nature, 2010, 463(7280): 501-506

[2]Deng X, Okram B, et al. Expanding the diversity of allosteric bcr-abl inhibitors. J Med Chem. 2010 Oct 14;53(19):6934-46.

[3]Reckel S, Hantschel O. Bcr-Abl: one kinase, two isoforms, two diseases. Oncotarget, 2017, 8(45): 78257-78258

[4]Meirson T, Genna A, Lukic N, et al. Targeting invadopodia-mediated breast cancer metastasis by using ABL kinase inhibitors. Oncotarget, 2018, 9(31): 22158-22183