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利尼伐尼 /Linifanib {[allProObj[0].p_purity_real_show]}

货号:A147574 同义名: ABT-869;AL-39324

Linifanib is a potent ATP-competitive VEGFR/PDGFR inhibitor for KDR, CSF-1R, Flt-1/3 and PDGFRβ with IC50 of 4 nM, 3 nM, 3 nM/4 nM and 66 nM respectively.

Linifanib 化学结构 CAS号:796967-16-3
Linifanib 化学结构
CAS号:796967-16-3
Linifanib 3D分子结构
CAS号:796967-16-3
Linifanib 化学结构 CAS号:796967-16-3
Linifanib 3D分子结构 CAS号:796967-16-3
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Linifanib 纯度/质量文件 产品仅供科研

货号:A147574 标准纯度: {[allProObj[0].p_purity_real_show]}
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产品名称 PDGFR PDGFRα PDGFRβ 其他靶点 纯度
Tyrphostin A9 +

PDGFR, IC50: 0.5 μM

EGFR 98%
Tyrphostin AG1296 99%+
Motesanib Diphosphate ++

PDGFR, IC50: 84 nM

98%
Pazopanib ++

PDGFR, IC50: 84 nM

99%
Imatinib +

PDGFR, IC50: 100 nM

c-Kit 98%
Imatinib Mesylate +

PDGFR, IC50: 100 nM

c-Kit 99%
Sennoside B 99%+
PP121 ++++

PDGFR, IC50: 2 nM

VEGFR,mTOR 99%+
Crenolanib ++++

PDGFRα, Kd: 2.1 nM

++++

PDGFRβ, Kd: 3.2 nM

99%+
Masitinib +

PDGFRα, IC50: 540 nM

+

PDGFRβ, IC50: 800 nM

99%+
Ki8751 ++

PDGFRα, IC50: 67 nM

c-Kit 98+%
Tivozanib ++

PDGFRα, IC50: 40 nM

++

PDGFRβ, IC50: 49 nM

99%+
Ponatinib ++++

PDGFRα, IC50: 1.1 nM

98%
Amuvatinib ++

PDGFRα (V561D), IC50: 40 nM

99%+
Axitinib +++

PDGFRα, IC50: 5.0 nM

++++

PDGFRβ, IC50: 1.6 nM

98%
CP-673451 +++

PDGFRα, IC50: 10 nM

++++

PDGFRβ, IC50: 1 nM

99%+
Telatinib +++

PDGFRα, IC50: 15 nM

c-Kit 99%+
Nintedanib ++

PDGFRα, IC50: 59 nM

++

PDGFRβ, IC50: 65 nM

99+%
Avapritinib ++++

PDGFRα (D842V), IC50: 0.5 nM

99%+
MK-2461 +++

PDGFRβ, IC50: 22 nM

98%+
Lactate +++

PDGFRβ, IC50: 27 nM

FLT3,c-Kit 85%
Linifanib ++

PDGFRβ, IC50: 66 nM

99%+
AZD2932 +++

PDGFRβ, IC50: 4 nM

c-Kit 98%
Dovitinib +++

PDGFRβ, IC50: 27 nM

FLT3,c-Kit 99%+
Sorafenib ++

mPDGFRβ, IC50: 57 nM

PDGFRβ, IC50: 57 nM

99%
Sunitinib ++++

PDGFRβ , IC50: 2 nM

FLT3 98%
Orantinib +++

PDGFRβ, Ki: 8 nM

99%+
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。
产品名称 VEGFR1 VEGFR2 VEGFR3 其他靶点 纯度
Motesanib Diphosphate ++++

VEGFR1, IC50: 2 nM

++++

VEGFR2, IC50: 3 nM

VEGFR2/Flk1, IC50: 3 nM

+++

VEGFR3, IC50: 6 nM

PDGFR,RET 98%
Tivozanib ++

VEGFR1, IC50: 30 nM

+++

VEGFR2, IC50: 6.5 nM

++

VEGFR3, IC50: 15 nM

99%+
Brivanib +

VEGFR1, IC50: 380 nM

++

VEGFR2, IC50: 25 nM

Flk1, IC50: 25 nM

99%+
Regorafenib +++

VEGFR1, IC50: 13 nM

+++

VEGFR2, IC50: 4.2 nM

+

VEGFR3, IC50: 46 nM

RET 98%
Pazopanib +++

VEGFR1, IC50: 10 nM

++

VEGFR2, IC50: 30 nM

+

VEGFR3, IC50: 47 nM

FGFR,PDGFR,c-Kit 99%
Sitravatinib +++

VEGFR1 (FLT1), IC50: 6 nM

+++

VEGFR2 (KDR), IC50: 5 nM

++++

VEGFR3 (FLT4), IC50: 2 nM

99%+
Foretinib +++

VEGFR1/FLT1, IC50: 6.8 nM

++++

KDR, IC50: 0.86 nM

++++

VEGFR3/FLT4, IC50: 2.8 nM

Tie-2 99%+
MGCD-265 analog ++++

VEGFR1, IC50: 3 nM

++++

VEGFR2, IC50: 3 nM

++++

VEGFR3, IC50: 4 nM

Tie-2 99%+
Lactate +++

VEGFR1/FLT1, IC50: 10 nM

+++

VEGFR2/Flk1, IC50: 13 nM

+++

VEGFR3/FLT4, IC50: 8 nM

FLT3,c-Kit 85%
AEE788 +

FLT1, IC50: 59 nM

+

KDR, IC50: 77 nM

EGFR 98+%
Linifanib ++++

VEGFR1/FLT1, IC50: 3 nM

++++

VEGFR2/KDR, IC50: 4 nM

+

VEGFR3/FLT4, IC50: 190 nM

FLT3 99%+
Vatalanib 2HCl +

VEGFR1/FLT1, IC50: 77 nM

++

VEGFR2/KDR, IC50: 37 nM

VEGFR2/Flk1, IC50: 270 nM

+

VEGFR3/FLT4, IC50: 660 nM

c-Kit,c-Fms 99%+
Axitinib ++++

VEGFR1/FLT1, IC50: 0.1 nM

++++

VEGFR2/KDR, IC50: 0.2 nM

VEGFR2/Flk1, IC50: 0.18 nM

98%
Dovitinib +++

VEGFR1/FLT1, IC50: 10 nM

+++

VEGFR2/Flk1, IC50: 13 nM

+++

VEGFR3/FLT4, IC50: 8 nM

FLT3,c-Kit 99%+
ZM 306416 +

VEGFR1, IC50: 0.33 μM

Src 99%+
KRN-633 +

VEGFR1, IC50: 170 nM

+

VEGFR2, IC50: 160 nM

+

VEGFR3, IC50: 125 nM

c-Kit,BTK 98%
OSI-930 +++

FLT1, IC50: 8 nM

+++

KDR, IC50: 9 nM

99%+
Lenvatinib ++

VEGFR1/FLT1, IC50: 22 nM

++++

VEGFR2/KDR, IC50: 4.0 nM

+++

VEGFR3/FLT4, IC50: 5.2 nM

98%
NVP-BAW2881 +

hVEGFR1, IC50: 820 nM

+++

mVEGF2, IC50: 165 nM

hVEGFR2, IC50: 9 nM

+

hVEGFR3, IC50: 420 nM

98%
Cediranib +++

VEGFR1/FLT1, IC50: 5 nM

++++

VEGFR2/KDR, IC50: 0.5 nM

c-Kit 99%+
Nintedanib ++

VEGFR1, IC50: 34 nM

+++

VEGFR2, IC50: 13 nM

+++

VEGFR3, IC50: 13 nM

FLT3 99+%
BMS-794833 ++

VEGFR2, IC50: 15 nM

99%+
SKLB1002 ++

VEGFR2, IC50: 32 nM

98%
Cabozantinib S-malate ++++

VEGFR2/KDR, IC50: 0.035 nM

99+%
Ki8751 ++++

VEGFR2, IC50: 0.9 nM

c-Kit 98+%
SU 5402 ++

VEGFR2, IC50: 20 nM

98%
Rivoceranib Mesylate ++++

VEGFR2, IC50: 1 nM

RET 98+%
Ponatinib ++++

VEGFR2, IC50: 1.5 nM

98%
LY2874455 +++

VEGFR2, IC50: 7 nM

99%+
ZM323881 HCl ++++

VEGFR2, IC50: <2 nM

98%
AZD2932 +++

VEGFR-2, IC50: 8 nM

c-Kit 98%
Cabozantinib ++++

VEGFR2/KDR, IC50: 0.035 nM

98%
Sorafenib ++

VEGFR2, IC50: 90 nM

VEGFR2/Flk1, IC50: 90 nM

99%
CYC-116 ++

VEGFR2, Ki: 44 nM

FLT3 99%+
Golvatinib ++

VEGFR2, IC50: 16 nM

99%+
Sunitinib +

VEGFR2 , IC50: 80 nM

FLT3 98%
RAF265 ++

VEGFR2, EC50: 30 nM

99%+
PD173074 99%+
BFH772 ++++

VEGFR2, IC50: 3 nM

98%
Semaxinib +

VEGFR2/Flk1, IC50: 1.23 μM

98%
Vandetanib ++

VEGFR2, IC50: 40 nM

+

VEGFR3, IC50: 110 nM

EGFR 98%
SAR131675 ++

VEGFR3, IC50: 23 nM

99%+
ENMD-2076 +

VEGFR2/KDR, IC50: 58.2 nM

++

VEGFR3/FLT4, IC50: 15.9 nM

FLT3,RET 98%
Telatinib +++

VEGFR2, IC50: 6 nM

++++

VEGFR3, IC50: 4 nM

c-Kit 99%+
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。

Linifanib 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]

Linifanib 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
mouse 3T3 cells Function assay Inhibition of VEGF-induced human KDR phosphorylation in mouse 3T3 cells by ELISA, IC50=0.004 μM 17343372

Linifanib 动物研究

Dose Mice: 25 mg/kg[3] (p.o., BID), 1.5 mg/kg - 15 mg/kg[1] (p.o.)
Administration p.o.
Pharmacokinetics
Animal Rats[4] Dogs[4] Monkeys[4]
Dose 5 mg/kg (i.v./p.o.) 2.5 mg/kg (i.v./p.o.) 2.5 mg/kg (i.v./p.o.)
Administration i.v.
p.o.
i.v.
p.o.
i.v.
p.o.
F 27% (p.o.) 47% (p.o.) 10.6% (p.o.)
Vd 1.1 L/kg (i.v.) 1.2 L/kg (i.v.) 2.2 L/kg (i.v.)
T1/2 3.6 h (i.v.) 2.0 h (i.v.) 3.1 h (i.v.)
AUC 6.8 µg·h/ml (p.o.) 1.5 µg·h/ml (p.o.) 0.6 µg·h/ml (p.o.)
CL 3.3 ml/min·kg (i.v.) 7.2 ml/min·kg (i.v.) 8.2 ml/min·kg (i.v.)

Linifanib 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 - -

Linifanib 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.

Linifanib 实验方案

计算器
存储液制备 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

Linifanib 技术信息

CAS号796967-16-3
分子式C21H18FN5O
分子量 375.399
别名 ABT-869;AL-39324
运输蓝冰
存储条件

液体 -20°C:3-6个月-80°C:12个月

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

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

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