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Linifanib

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Chemical Structure| 796967-16-3 同义名 : ABT-869;AL-39324
CAS号 : 796967-16-3
货号 : A147574
分子式 : C21H18FN5O
纯度 : 99%+
分子量 : 375.399
MDL号 : MFCD11840918
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: 12 mg/mL(31.97 mM)，配合低频超声助溶，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：

5%DMSO+40%PEG 300+5%Tween80+50%water 10 mg/mL

生物活性
靶点

  • VEGFR1

    VEGFR1/FLT1, IC50:3 nM

  • VEGFR3

    VEGFR3/FLT4, IC50:190 nM

  • VEGFR2

    VEGFR2/KDR, IC50:4 nM

  • PDGFRβ

    PDGFRβ, IC50:66 nM
描述 Linifanib is a muti-target inhibitor with IC50 values of 3nM, 3nM, 4nM, 4nM, 14nM and 66nM for VEGFR1, CSF-1R, VEGFR2, FLT3, c-Kit and PDGFRβ(measured by kinase assays), respectively. Linifanib showed in cellular inhibition on ligand-induced phosphorylation of PDGFR-βKDR and CSF-1R with IC50 values of 2nM, 31nM and 10nM, respectively, in 3T3 transfectants, as well as VEGF-induced proliferation with IC50 value of 0.2nM for human endothelial cells[1]. The in vivo study showed that, consistent with the inhibition of VEGFR and PDGFRβby Linifanib, oral administration of Linifanib at dose of 7.5 and 15mg/kg, BID, significantly inhibited bFGF- and VEGF-induced increases of vessel density in the cornea. Oral treatment with Linifanib at dose ranging in 1.5-12.5mg/kg, BID, could significantly reduce the tumor growth or in several orthotopic tumor models, including MDA-231 and MDA-435LM xenograft mice and rat glioma, or enhance the anti-tumor effect of paclitaxel in the models[1].
作用机制 Linifanib can bind to the ATP-binding site of CSF-1R.[2]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human MOLM13 cells Cytotoxicity assay 72 h Cytotoxicity against human MOLM13 cells harboring mutant FLT3 after 72 hrs by MTS assay, GI50=0.037 μM 23618709
human MOLT4 cells Proliferation assay 72 h Antiproliferation activity against human MOLT4 after 72 hrs by MTS method, GI50=6.7 μM 21708468
human MV4-11 cells Proliferation assay 72 h Antiproliferation activity against FLT3/ITD harboring human MV4-11 cells after 72 hrs by MTS method, GI50=0.04 μM 21708468
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT03481842 Endometriosis ... 展开 >> Endometriosis Ovary Endometriosis Externa Endometriosis, Rectum 收起 << Phase 1 Phase 2 Not yet recruiting September 30, 2018 Switzerland ... 展开 >> BioGene Pharmaceutical Ltd. Not yet recruiting Basel, Вâlе, Switzerland, 4057 Contact: J. Łanevska, Dr       jula.edu@yahoo.com 收起 <<
NCT00707889 Advanced Colorectal Cancer ... 展开 >> Adenocarcinoma of the Colon Adenocarcinoma of the Rectum 收起 << Phase 2 Completed - -
NCT00716534 Advanced or Metastatic Non-Sma... 展开 >>ll Cell Lung Cancer 收起 << Phase 2 Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.66mL

0.53mL

0.27mL

13.32mL

2.66mL

1.33mL

26.64mL

5.33mL

2.66mL
参考文献

[1]Albert DH, Tapang P, et al. Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther. 2006;5(4):995-1006.

[2]Guo J, Marcotte PA, et al. Inhibition of phosphorylation of the colony-stimulating factor-1 receptor (c-Fms) tyrosine kinase in transfected cells by ABT-869 and other tyrosine kinase inhibitors. Mol Cancer Ther. 2006;5(4):1007-13.

[3]Jiang F, Albert DH, et al. ABT-869, a multitargeted receptor tyrosine kinase inhibitor, reduces tumor microvascularity and improves vascular wall integrity in preclinical tumor models. J Pharmacol Exp Ther. 2011 Jul;338(1):134-42.

[4]Dai Y, Hartandi K, et al. Discovery of N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N'-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-aminoindazole-based orally active multitargeted receptor tyrosine kinase inhibitor. J Med Chem. 2007 Apr 5;50(7):1584-97. Epub 2007 Mar 8.