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Vandetanib/凡德他尼 {[allProObj[0].p_purity_real_show]}

货号:A126372 同义名: 凡德他尼(ZD6474) / ZD6474; CH 331

Vandetanib(D6474)是一种有效的口服活性VEGFR2/KDR酪氨酸激酶抑制剂,IC50为40 nM。凡德他尼还抑制VEGFR3/FLT4(IC50=110 nM)和EGFR/HER1(IC50=500 nM)的酪氨酸激酶活性。

Vandetanib/凡德他尼 化学结构 CAS号:443913-73-3
Vandetanib/凡德他尼 化学结构
CAS号:443913-73-3
Vandetanib/凡德他尼 3D分子结构
CAS号:443913-73-3
Vandetanib/凡德他尼 化学结构 CAS号:443913-73-3
Vandetanib/凡德他尼 3D分子结构 CAS号:443913-73-3
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Vandetanib/凡德他尼 纯度/质量文件 产品仅供科研

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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

RET,PDGFR 97%
Tivozanib ++

VEGFR1, IC50: 30 nM

+++

VEGFR2, IC50: 6.5 nM

++

VEGFR3, IC50: 15 nM

99%+
Brivanib +

VEGFR1, IC50: 380 nM

++

Flk1, IC50: 25 nM

VEGFR2, 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

c-Kit,PDGFR,FGFR 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

c-Kit,FLT3 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/Flk1, IC50: 270 nM

VEGFR2/KDR, IC50: 37 nM

+

VEGFR3/FLT4, IC50: 660 nM

c-Kit,c-Fms/CSF1R 99%+
Axitinib ++++

VEGFR1/FLT1, IC50: 0.1 nM

++++

VEGFR2/Flk1, IC50: 0.18 nM

VEGFR2/KDR, IC50: 0.2 nM

98%
Dovitinib +++

VEGFR1/FLT1, IC50: 10 nM

+++

VEGFR2/Flk1, IC50: 13 nM

+++

VEGFR3/FLT4, IC50: 8 nM

c-Kit,FLT3 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

+++

hVEGFR2, IC50: 9 nM

mVEGF2, IC50: 165 nM

+

hVEGFR3, IC50: 420 nM

99%
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

99%
Cabozantinib S-malate ++++

VEGFR2/KDR, IC50: 0.035 nM

99+%
Ki8751 ++++

VEGFR2, IC50: 0.9 nM

c-Kit 99%
SU 5402 ++

VEGFR2, IC50: 20 nM

98%
Apatinib 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 99%
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 99%
SAR131675 ++

VEGFR3, IC50: 23 nM

99%+
ENMD-2076 +

VEGFR2/KDR, IC50: 58.2 nM

++

VEGFR3/FLT4, IC50: 15.9 nM

RET,FLT3 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。

Vandetanib/凡德他尼 生物活性

靶点
  • EGFR/ErbB1

    EGFR, IC50:500 nM

  • VEGFR3

    VEGFR3, IC50:110 nM

  • VEGFR2

    VEGFR2, IC50:40 nM

描述 VEGF/VEGFR (vascular endothelial growth factor vascular endothelial growth factor receptor) pathway plays a key role in tumor angiogenesis by promotion of vascular and lymphatic endothelial, as well as survival, and invasion, thus resulting in neovascularization, tumor growth and metastasis. Vandetanib is a selective VEGFR2 inhibitor with IC50 value of 40nM versus IC50 of 110nM/1600nM for VEGFR3/VEGFR1, also show inhibitory potency to EGFR, PDGFRβ, Tie-2 and FGFR1 with IC50 values of 0.5μM, 1.1μM, 2.5μM and 3.6μM, respectively, in kinase activity assays. Consistent with the selectivity for inhibition of the different RTKs, Vandetanib showed most potency to VEGF-stimulated HUVEC proliferation with IC50 value of 60nM, versus IC50 values of 170 and 800nM for EGF- and bFGF-stimulated cell growth, respectively[1]. The inactivation by Vandetanib on kinase activity of its targets was confirmed by the cellular studies as exposure to Vandetanib at concentration of 1, 5 and 10μM caused inhibition of VEGF-induced p-VEGFR2 in HUVECs, as well as suppressed EGF-induced p-EGFR in the hepatoma cell lines[2]. Vandetanib showed anti-proliferative effect on A549 tumor cells at concentration ranging in 2.7±0.5μM and Calu-6 tumor cells at concentration ranging in 13.5±1.5μM, 45- and 225-fold more than those to inhibit VEGF-stimulated HUVEC proliferation. As prediction of its effect on VEGFR, the significant anti-angiogenesis by Vandetanib can be observed in mice intradermally implanted A549 tumor cells with reduction of tumor-induced blood vessel formation by 63%/79% at dose of 50/100mg/kg/day, orally, for 5 days. Oral administration of Vandetanib once daily produced anti-tumor effect in a dose-dependent manner in all tested models from different origins, including Calu-6 (lung), PC-3 (prostate), MDA-MB-231 (breast), SKOV-3 (ovary), SW620 (colon), A549 (lung), A431 (vulva), B16-F10(AP3) (murine melanoma) and Lewis Lung (murine lung) xenografts, at dose of 12.5, 25, 50 and 100mg/kg[1].
作用机制 Vandetanib is an ATP-competitive inhibitor of VEGFR, EGFR and RET kinases.[3]

Vandetanib/凡德他尼 细胞实验

Cell Line
Concentration Treated Time Description References
A2780 cells 500, 750, 1000, 2000, 5000 nM 72 h To test the inhibitory effect of Vandetanib on A2780 cells expressing RET mutants, the results showed that Vandetanib significantly reduced cell viability in a dose-dependent manner. J Exp Clin Cancer Res. 2020 Mar 23;39(1):53.
CALU-3 cells 1 μM 12 months To study the acquired resistance mechanisms of CALU-3 cells to Vandetanib, results showed that CALU-3 cells developed acquired resistance after long-term exposure to Vandetanib, accompanied by epithelial-mesenchymal transition (EMT) features. Br J Cancer. 2011 Jul 26;105(3):382-92.
HEK293T cells 10 μM 44 h Vandetanib remarkably reduced SARS-CoV-2 propagation and restored SARS-CoV-2-induced aberrant OXPHOS process and ATP generation. Signal Transduct Target Ther. 2024 May 11;9(1):125.
8505C 0.59-150 μM 72 h Vandetanib significantly inhibited the proliferation of 8505C cells, with a GI50 value of 7.56 μM. Clin Cancer Res. 2011 Apr 15;17(8):2281-91.
Hth83 0.59-150 μM 72 h Vandetanib significantly inhibited the proliferation of Hth83 cells, with a GI50 value of 3.30 μM. Clin Cancer Res. 2011 Apr 15;17(8):2281-91.
K562 cells 0.78, 1.56, 3.12 μM 48 h Vandetanib downregulated EPHB4 protein via the ubiquitin-proteasome pathway and inhibited PI3K/AKT and MAPK/ERK signaling pathways in K562 cells. Mol Oncol. 2022 Jul;16(14):2747-2765.
H9 cells 0.78, 1.56, 3.12 μM 48 h Vandetanib significantly inhibited the growth of H9 cells, and its effect was correlated with the expression level of EPHB4. Mol Oncol. 2022 Jul;16(14):2747-2765.
MEG-01 cells 0.30, 0.60, 1.20 μM 48 h Vandetanib significantly inhibited the growth of MEG-01 cells and induced apoptosis. Mol Oncol. 2022 Jul;16(14):2747-2765.
MCF-7 10 μM 48 h To evaluate the effect of Vandetanib on RET signaling pathway in hormone-sensitive MCF-7 cells and its impact on cell viability. Results showed that Vandetanib significantly reduced phosphorylated RET levels and cell viability without altering total RET expression. Additionally, Vandetanib enhanced the inhibitory effect of Tamoxifen. Clin Cancer Res. 2014 Apr 15;20(8):2115-25.
BT-474 10 μM 48 h To evaluate the effect of Vandetanib on RET signaling pathway in hormone-resistant BT-474 cells and its impact on cell viability. Results showed that Vandetanib significantly reduced phosphorylated RET levels and cell viability without altering total RET expression. Additionally, Vandetanib enhanced the inhibitory effect of Tamoxifen. Clin Cancer Res. 2014 Apr 15;20(8):2115-25.
HCC827 cells 1 μM Vandetanib almost completely diminished EGFR phosphorylation in HCC827 cells. Clin Cancer Res. 2009 May 15;15(10):3484-94.
A549 cells 1 μM Vandetanib caused only a partial reduction in EGFR activation in A549 cells. Clin Cancer Res. 2009 May 15;15(10):3484-94.
H1975 cells 1 μM Neither erlotinib nor vandetanib treatment resulted in significant decreases in EGFR phosphorylation in H1975 cells. Clin Cancer Res. 2009 May 15;15(10):3484-94.

Vandetanib/凡德他尼 动物实验

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice CALU-3 cell xenograft model Oral 15 mg/kg Twice daily, 5 days per week, for 5 weeks To evaluate the antitumour efficacy of the MEK inhibitor MSC19363669B in the CALU-3 cell xenograft model, results showed that MSC19363669B significantly inhibited tumour growth. Br J Cancer. 2011 Jul 26;105(3):382-92.
HACE2 transgenic mice SARS-CoV-2 infection model Oral 25 mg/kg Once daily for 6 days Vandetanib significantly reduced SARS-CoV-2 propagation in lung tissue and mitigated SARS-CoV-2-induced lung inflammation. Signal Transduct Target Ther. 2024 May 11;9(1):125.
Nude mice ATC xenograft model Oral gavage 50 mg/kg, 25 mg/kg Daily for 3-4 weeks Vandetanib significantly inhibited the growth of ATC xenograft tumors, with tumor volume reductions of 69.32% and 66.56% for Hth83 and 8505C, respectively. Clin Cancer Res. 2011 Apr 15;17(8):2281-91.
BALB/c-nu mice K562 xenograft model Oral 40 mg/kg Once daily for 14 days Vandetanib significantly inhibited tumor growth in the K562 xenograft model and induced tumor cell apoptosis. Mol Oncol. 2022 Jul;16(14):2747-2765.
Mice MCF-7 xenograft model Oral 25 mg/kg Daily for 3 weeks To evaluate the effect of Vandetanib on tumor growth and metastasis in the MCF-7 xenograft model. Results showed that Vandetanib significantly inhibited tumor growth and reduced tumor cells in the lung. Additionally, Vandetanib reduced activation of ERK1/2 and AKT and increased tumor cell apoptosis. Clin Cancer Res. 2014 Apr 15;20(8):2115-25.
Nude mice NSCLC xenograft models Oral 50 mg/kg Daily Vandetanib significantly inhibited tumor growth in the HCC827 xenograft model, even showing complete tumor regression in larger tumors. In the HCC827-T790M model, vandetanib delayed the emergence of resistance. In the A549 model, vandetanib and bevacizumab/erlotinib combination therapy were more effective than erlotinib or bevacizumab alone. In the H1975 model, both vandetanib and bevacizumab significantly inhibited tumor growth. Clin Cancer Res. 2009 May 15;15(10):3484-94.
Mice MYCN/AlkF1178L neuroblastoma model Oral 30 mg/kg Daily treatment To evaluate the inhibitory effect of the combination of crizotinib and vandetanib on MYCN/AlkF1178L neuroblastoma, the results showed that the combination therapy was more effective than crizotinib alone, significantly inhibiting tumor growth and prolonging the survival of mice. Oncogene. 2018 Mar;37(11):1417-1429.

Vandetanib/凡德他尼 动物研究

Dose Rat: 30.8 mg/kg[5] (p.o.) Mice: 25 mg/kg[6] (o.g., i.p.), 12.5 mg/kg- 50 mg/kg[4] (p.o.)
Administration p.o., o.g., i.p.
Pharmacokinetics
Animal Rats[7]
Dose 5 mg/kg (male)
Administration i.v. or p.o.
F 91.8% (p.o.)
T1/2 15.6 h (i.v.)
19.6 h (p.o.)
AUC0→36h 2920 ng·h/ml (i.v.)
2680 ng·h/ml (p.o.)
Tmax 3.0 h (p.o.)
Cmax 142 ng/ml (p.o.)
AUC 3560 ng·h/ml (i.v.)
3530 ng·h/ml (p.o.)

Vandetanib/凡德他尼 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
NCT02142036 Metastatic Cancer Phase 2 Active, not recruiting January 2022 Norway ... 展开 >> Akershus University Hospital Lillestrøm, Norway, 1478 The Norwegian Radium Hospital Oslo, Norway, 0379 收起 <<
NCT03413176 - Completed - France ... 展开 >> AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM. Paris, France, 75013 收起 <<
NCT02788201 Urothelial Carcinoma ... 展开 >> Bladder Cancer Urinary Bladder Neoplasms 收起 << Phase 2 Recruiting July 1, 2020 United States, Maryland ... 展开 >> National Institutes of Health Clinical Center Recruiting Bethesda, Maryland, United States, 20892 Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937 收起 <<

Vandetanib/凡德他尼 参考文献

[1]Vitagliano D, De Falco V, et al. The tyrosine kinase inhibitor ZD6474 blocks proliferation of RET mutant medullary thyroid carcinoma cells. Endocr Relat Cancer. 2010 Nov 30;18(1):1-11.

[2]Wedge SR, Ogilvie DJ, et al. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res. 2002 Aug 15;62(16):4645-55.

[3]Inoue K, Torimura T, et al. Vandetanib, an inhibitor of VEGF receptor-2 and EGF receptor, suppresses tumor development and improves prognosis of liver cancer in mice. Clin Cancer Res. 2012 Jul 15;18(14):3924-33.

[4]Yoshikawa D, Ojima H, et al. Vandetanib (ZD6474), an inhibitor of VEGFR and EGFR signalling, as a novel molecular-targeted therapy against cholangiocarcinoma. Br J Cancer. 2009;100(8):1257-66.

[5]Attwa MW, Kadi AA, et al. Identification and characterization of in vivo, in vitro and reactive metabolites of vandetanib using LC-ESI-MS/MS. Chem Cent J. 2018 Sep 24;12(1):99.

[6]Pozo K, Zahler S, et al. Preclinical characterization of tyrosine kinase inhibitor-based targeted therapies for neuroendocrine thyroid cancer. Oncotarget. 2018 Dec 28;9(102):37662-37675.

[7]ZD6474

Vandetanib/凡德他尼 实验方案

计算器
存储液制备 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.10mL

0.42mL

0.21mL

10.52mL

2.10mL

1.05mL

21.04mL

4.21mL

2.10mL

Vandetanib/凡德他尼 技术信息

CAS号443913-73-3
分子式C22H24BrFN4O2
分子量 475.35
SMILES Code CN1CCC(COC2=CC3=NC=NC(NC4=CC=C(Br)C=C4F)=C3C=C2OC)CC1
MDL No. MFCD07772346
别名 凡德他尼(ZD6474) ;ZD6474; CH 331; Zactima
运输蓝冰
InChI Key UHTHHESEBZOYNR-UHFFFAOYSA-N
Pubchem ID 3081361
存储条件

In solvent -20°C: 3-6个月 -80°C: 12个月

Pure form Keep in dark place, inert atmosphere, store in freezer, under -20°C

溶解方案

DMSO: 20 mg/mL(42.07 mM),配合低频超声,并水浴加热至45℃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

请根据您的动物给药指南选择适当的溶解方案。
以下溶解方案都请先按照体外实验的方式配制澄清的储备液,再依次添加助溶剂:
——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议现用现配,当天使用; 以下溶剂前显示的百分比是指该溶剂在终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶
方案 一
方案 二
配制的工作液建议现用现配,短期内尽快用完。 以下溶剂前显示的百分比是指该溶剂在终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶
方案 一
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