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。


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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。 | |||||||||||||||||||
| 靶点 |
|
| 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] |
| 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. | |
| 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. |
| 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 |
|
| 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 << |
| 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 |
|
| 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 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
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