|N-(2-羟乙基)-3-(6-((4-(三氟甲氧基)苯基)氨基)嘧啶-4-基)苯甲酰胺|CsnPharm

CAS No.: 778277-15-9

N-(2-Hydroxyethyl)-3-(6-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-4-yl)benzamide Catalog No. CSN12398

Synonyms: N/A

GNF-5 is a selective non-ATP competitive inhibitor of Bcr-Abl with IC50 of 220 nM, it's an analogue of GNF-2 with improved pharmacokinetic properties.

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实验方案

技术信息

生物活性

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].
动物研究
剂量
Mice: 75 mg/kg^[1] (p.o., BID), 100 mg/kg^[3] (p.o.)

给药途径
p.o.
参考文献

动物研究
剂量	Mice: 75 mg/kg^[1] (p.o., BID), 100 mg/kg^[3] (p.o.)
给药途径	p.o.

[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

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.3902 mL
- 11.9512 mL
- 23.9023 mL
- 5 mM
- 0.4780 mL
- 2.3902 mL
- 4.7805 mL
- 10 mM
- 0.2390 mL
- 1.1951 mL
- 2.3902 mL

技术信息

CAS号

778277-15-9

储存条件

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

液体: -20°C:3-6 月 -80°C:12月

分子式

C20H17F3N4O3

运输

蓝冰

分子量

418.37

别名

N/A

溶解度

DMSO	150.0 mg/mL (358.5 mM)
Water	insoluble

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

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N-(2-Hydroxyethyl)-3-(6-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-4-yl)benzamide Catalog No. CSN12398

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