Vandetanib (ZD6474)

Catalog No.S1046

Vandetanib (ZD6474) Chemical Structure

Molecular Weight(MW): 475.35

Vandetanib (ZD6474) is a potent inhibitor of VEGFR2 with IC50 of 40 nM in a cell-free assay.

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5 Customer Reviews

  • Cell, 2016, 165(1):234-46.. Vandetanib (ZD6474) purchased from Selleck.

    Vandetanib reduced extracellular nitrite levels in endothelial cells. MS1 endothelial cells (ECs) were incubated with 1 mol/L of vandetanib or matched vehicle (dimethyl sulfoxide [DMSO]), 50 ng/mL of vascular endothelial growth factor (VEGF) or matched vehicle (PBS; 0.5 hours), and L-arginine and soluble N-ethylmaleamide sensitive factor attachment protein (SNAP) added (1.5 hours). Vandetanib lowered nitrite levels in MS1 Ecs (*P0.0003). VEGF was used a positive control and increased nitrite levels (**P0.02). These findings indicate that vandetanib lowered endothelial cell NO levels.

    hypertension 2011 58, 85-92. Vandetanib (ZD6474) purchased from Selleck.

  • Vandetanib reduced phosphorylation of Akt in endothelial cells (ECs). MS1 ECs were incubated with 1 μmol/L of vandetanib or matched vehicle (dimethyl sulfoxide [DMSO]; 1 hour). Western blotting analysis showed that vandetanib decreased phosphorylation of Akt (S473) in MS1 ECs (*P<0.01; n=6 per group, studies done in triplicate). These findings show that vandetanib reduced Akt activity.

    hypertension 2011 58, 85-92. Vandetanib (ZD6474) purchased from Selleck.

    Vandetanib increases membrane localization of endothelial NO synthase (eNOS). MS1 endothelial cells (ECs) were incubated with 1 μmol/L of vandetanib or matched vehicle (dimethyl sulfoxide [DMSO]). Western blotting analysis showed that vandetanib increases membrane localization of eNOS compared with control (*P<0.04; n=4 per group, studies done in triplicate). These findings show that vandetanib increased the membrane localization of eNOS compared with control.

    hypertension 2011 58, 85-92. Vandetanib (ZD6474) purchased from Selleck.

  • Breast cancer cells were pretreated with 100ng/ml EGF for 15 min and then treated with the indicated concentrations of Vandetanib for 24 hours.

     

     

    Dr. Zhang of Tianjin Medical University. Vandetanib (ZD6474) purchased from Selleck.

Purity & Quality Control

Choose Selective VEGFR Inhibitors

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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

Biological Activity

Description Vandetanib (ZD6474) is a potent inhibitor of VEGFR2 with IC50 of 40 nM in a cell-free assay.
Targets
VEGFR2 [1]
(Cell-free assay)
40 nM
In vitro

Vandetanib also inhibits VEGFR3 and EGFR with IC50 of 110 nM and 500 nM, respectively. Vandetanib is not sensitive to PDGFRβ, Flt1, Tie-2 and FGFR1 with IC50 of 1.1-3.6 μM, while almost has no activity against MEK, CDK2, c-Kit, erbB2, FAK, PDK1, Akt and IGF-1R with IC50 above 10 μM. Vandetanib inhibits VEGF-, EGF- and bFGF-stimulated HUVEC proliferation with IC50 of 60 nM, 170 nM and 800 nM, with no effect on basal endothelial cell growth. Vandetanib inhibits tumor cell growth with IC50 of 2.7 μM (A549) to 13.5 μM (Calu-6). [1] Vandetanib displays an inhibitory effect on the basal ABCG2-ATPase. Parental and ABCG2-expressing A431 cells showed similar sensitivities toward Vandetanib. Exposure to EGFR inhibitors decreases pEGFR levels in A431 cells, with Vandetanib displaying only a moderate effect. Vandetanib displays a slight but measurable effect, whereas gefitinib, pelitinib and neratinib completely inhibit ABCG2-mediated efflux of mitoxantrone from A431/ABCG2 cells, similarly to the specific ABCG2 inhibitor Ko143. [2] Vandetanib inhibits both PC3wt and PC3R cell lines with similar IC50 of 13.3 μM and 11.5 μM, respectively. [3] Vandetanib suppresses phosphorylation of VEGFR2 in HUVEC and EGFR in hepatoma cells and inhibits cell proliferation. [4] Vandetanib causes an accumulation of cells in the G0-G1 phases in GEO and OVCAR-3 cells and increases apoptosis in OVCAR-3, ZR-75-1, MCF-10A ras, and GEO cells. Vandetanib causes a dose-dependent inhibition of EGFR phosphorylation in mouse NIH-EGFR fibroblasts and human MCF-10A ras breast cancer cells, two cell lines that overexpress the human EGFR. Vandetanib treatment results in a dose-dependent inhibition of soft agar growth in seven human cell lines (breast, colon, gastric, and ovarian) with functional EGFR but lacking VEGFR2. [5]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SN179  MmDrSpVv[3Srb36gRZN{[Xl? NEPtPVU2ODEkgJnuUeKh MWWxOkBp MmmzbY5kemWjc3XzJGNZS1J2IHX4dJJme3Orb36gd4lodmmoaXPhcpRtgQ>? M{G2WFI2Pjd4Nkmx
SN186 NGfoOZhHfW6ldHnvckBCe3OjeR?= M3XS[lUxOOLCiX7NxsA> MlXhNVYhcA>? M4nEb4lv[3KnYYPld{BEYEOUNDDlfJBz\XO|aX;uJJNq\26rZnnjZY51dHl? MWeyOVY4PjZ7MR?=
SN179  NEnnV|FHfW6ldHnvckBCe3OjeR?= MU[1NFDjiImwTdMg M1HVXFE3KGh? NVPpTHJ[\W6qYX7j[ZMhfGinIFPYR2wyOiCmaYLlZ5Rm\CCvaXfyZZRqd25? NXraOHp[OjV4N{[2PVE>
SN179  MormSpVv[3Srb36gRZN{[Xl? MmnzOVAx6oDLbl5CpC=> NVyzPGpSOTZiaB?= MUnpcoNz\WG|ZYOgZoF{[WxibXnndoF1cW:wwrC= MonWNlU3PzZ4OUG=
Jurkat MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHfpcJQ4OsLiaNMg MXrHTVUxRTFwNTFCtUAxNjJizszN MXeyOFY5OTJyNR?=
K-562 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYDOfGx1PzMEoHlCpC=> NYnxUWt1T0l3ME2xMlghyrFiMD6xJO69VQ>? MXuyOFY5OTJyNR?=
NCTC-2544 NIPjeoJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3L4V|czyqCqwrC= NVH5O2xNT0l3ME20MlYhyrFiMD6zJO69VQ>? M4XZU|I1PjhzMkC1
A-431 NHXpNoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEO3ZoU4OsLiaNMg MoLmS2k2OD1{LkSgxtEhOC5|IN88US=> M3;XT|I1PjhzMkC1
SK-N-SH NFSwdoFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXHKbYVmOC54MkWtNlAh|ryP NVrjVnZ2PDhiaB?= NYXSSFc5TE2VTx?= MYjpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NIjB[YszPDN7OUC3OC=>
SH-SY5Y M4j1eWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn3DNE43OjVvMkCg{txO NHPnWFM1QCCq M4nIZ2ROW09? NXvkU4xicW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NXXLZVN5OjR|OUmwO|Q>
SK-N-SH Mnn3RZBweHSxc3nzbUBCe3OjeR?= MYO1M|ExNzJyIN88US=> NFLSWWo1QCCq NYL3[YgxTE2VTx?= NXK2W3I{cW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> M3;yfFI1Ozl7MEe0
SH-SY5Y MkDXRZBweHSxc3nzbUBCe3OjeR?= MXi1M|ExNzJyIN88US=> M{fielQ5KGh? M33VR2ROW09? MojMbY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= MUGyOFM6QTB5NB?=
SK-N-SH M2\OSGZ2dmO2aX;uJGF{e2G7 MYC1M|ExNzJyIN88US=> MXO0PEBp NYL3OpE5TE2VTx?= MnuwbY5lfWOnczDHNUBxcGG|ZTDj[YxtKGO7Y3zlJIFzemW|dB?= NVT3cm1zOjR|OUmwO|Q>
SH-SY5Y MXLGeY5kfGmxbjDBd5NigQ>? M3:1TFUwOTBxMkCg{txO NGrJXJo1QCCq M4LBXmROW09? NIT4WJFqdmS3Y3XzJGcyKHCqYYPlJINmdGxiY4njcIUh[XK{ZYP0 NFvXcYwzPDN7OUC3OC=>
SK-N-SH MUDGeY5kfGmxbjDBd5NigQ>? NVnPToVpOS93L{GwJO69VQ>? NVr4PFZiPDhiaB?= MXfEUXNQ MoD4bY5pcWKrdIOgVmVVKHCqb4PwbI9zgWyjdHnvci=> NHuwdIgzPDN7OUC3OC=>
SH-SY5Y NEDZ[5RHfW6ldHnvckBCe3OjeR?= NYn0SYpzOS93L{GwJO69VQ>? NXrSPYxOPDhiaB?= MlnuSG1UVw>? NVfzcY9xcW6qaXLpeJMhWkWWIIDoc5NxcG:{eXzheIlwdg>? NIfJZ5IzPDN7OUC3OC=>
SK-N-SH NFHsTXpHfW6ldHnvckBCe3OjeR?= NYOxZ3hZPS9zMDFOwG0> NX\0U5ViPDhiaB?= M{HkPWROW09? M332XIlvcGmkaYTzJIh2dWGwIF7CJINmdGxibXnndoF1cW:w M4fQZVI1Ozl7MEe0
SH-SY5Y NXHmWZdZTnWwY4Tpc44hSXO|YYm= M{f5OlUwOTBizszN MmnMOFghcA>? NU[z[lE5TE2VTx?= NEDDfJVqdmirYnn0d{BpfW2jbjDORkBk\WyuIH3p[5JifGmxbh?= MmTZNlQ{QTlyN{S=
SK-N-SH NVHYTm1qTnWwY4Tpc44hSXO|YYm= MWm1M|ExKM7:TR?= M4jIVFQ5KGh? Mn3XSG1UVw>? Mo\pbY5pcWKrdIOgbJVu[W5iTlKgZ4VtdCCrbo\hd4lwdg>? NFjZ[o0zPDN7OUC3OC=>
SH-SY5Y Mn3RSpVv[3Srb36gRZN{[Xl? M3vZNlUwOTBizszN MofPOFghcA>? MVfEUXNQ NU\5OnZucW6qaXLpeJMhcHWvYX6gUmIh[2WubDDpcpZie2mxbh?= MWqyOFM6QTB5NB?=
SK-N-SH NYDrVoIzTnWwY4Tpc44hSXO|YYm= MYS1JO69VQ>? NY\pVHp[OjRxNEivO|IhcA>? NVGyPHVITE2VTx?= NIXle2R{fXCycnXzd4V{KHSqZTDlfJBz\XO|aX;uJI9nKEO[Q2K0JIFv\CCPTWCxOEBuWk6D NFP2OXgzPDN7OUC3OC=>
SH-SY5Y NEjmS5FHfW6ldHnvckBCe3OjeR?= NXPEToR7PSEQvF2= NETV[|kzPC92OD:3NkBp NHnLS3dFVVOR NEDoTIR{fXCycnXzd4V{KHSqZTDlfJBz\XO|aX;uJI9nKEO[Q2K0JIFv\CCPTWCxOEBuWk6D NX[zN2d2OjR|OUmwO|Q>
SK-N-SH M2XCN2Z2dmO2aX;uJGF{e2G7 NIHHemM2KM7:TR?= NE\6NHI1QC95MjDo NGP2bXlFVVOR NHPBZW5{fXCycnXzd4V{KGW6cILld5Nqd25ib3[geIhmKEO[Q2K0JIFv\CCPTWCxOEBxem:2ZXnu NVrhTVlUOjR|OUmwO|Q>
SH-SY5Y MmDtSpVv[3Srb36gRZN{[Xl? M{T2U|Uh|ryP MoGxOFgwPzJiaB?= MWDEUXNQ MUjzeZBxemW|c3XzJIV5eHKnc4Ppc44hd2ZidHjlJGNZS1J2IHHu[EBOVVBzNDDwdo91\Wmw NGHkVXAzPDN7OUC3OC=>
HMEpC NHu3T4hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUe3ZnNSOSCwTT2xNFAh|ryP NEPVcGY1QMLiaNMg M2DOeGROW09? NYnnO4hFcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M{D2W|I1OTN6OESz
MCF-7 NWf5XIF7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVOxJI5ONTFyMDFOwG0> MX20POKhcMLi M4XabGROW09? MUnpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NWGzO5ZROjRzM{i4OFM>
ZR-75-1 M{KxRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV;uPWJHOSCwTT2xNFAh|ryP Mlm2OFjDqGkEoB?= MUTEUXNQ MUDpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NHHm[2ozPDF|OEi0Ny=>
MDA-MB-231 MmewS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnPUNUBvVS1zMECg{txO NXTDdJc3PDkEoHlCpC=> NHH0cFNFVVOR MkKybY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M1zvXlI1OTN6OESz
MDA-MB-468 NHP6fFJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWqxJI5ONTFyMDFOwG0> M1rkdlQ5yqCqwrC= MX7EUXNQ NIHkVHFqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? Mm\lNlQyOzh6NEO=
T-47-D NWTSfXBzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXixJI5ONTFyMDFOwG0> MUe0POKhcMLi MnjBSG1UVw>? MmPSbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NE[1SJczPDF|OEi0Ny=>
U251  MkTESpVv[3Srb36gRZN{[Xl? NH;FVHkzNzRxOPMAje696oT|wrC= NG\HW3o3NzF{L{K0JIg> MlvySG1UVw>? NWfpW24{cW6lcnXhd4V{KHSqZTDMR|MuUUlibHX2[YwhcW5iYTD0bY1mNWSncHXu[IVvfCCjbnSg[I9{\S2mZYDlcoRmdnRibXHucoVz NXvsTIw1OjN5OUm4OVI>
U87MG NYjydlhyTnWwY4Tpc44hSXO|YYm= NFPI[FYzNzRxOPMAje696oT|wrC= MlmyOk8yOi9{NDDo M3PrOGROW09? NEXmTFVqdmO{ZXHz[ZMhfGinIFzDN{1KUSCuZY\lcEBqdiCjIITpcYUu\GWyZX7k[Y51KGGwZDDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> Mm\ENlM4QTl6NUK=
U251  NFLSPFBHfW6ldHnvckBCe3OjeR?= MWe05qCK|r{khMRCpC=> NFHrTWEzNzZxMUKgbC=> Mo\wSG1UVw>? NH7aT4Z{fXCycnXzd4V{KGKjc3HsJIxmfmWuczDv[kBxcG:|cHjvdplt[XSrb36gc4YhWzZiKGOyN|UwOjN4KTygOGUuSlBzIDjUN|cwPDZrLDDhcoQhSWu2IDjTOFc{MSCrbjDhJJRqdWVvZHXw[Y5l\W62IH3hco5mesLi NHnZcGozOzd7OUi1Ni=>
U87MG NGD6dXNHfW6ldHnvckBCe3OjeR?= NHq0bnE16oDLzs|iiNPDqA>? Ml\kNk83NzF{IHi= MmrmSG1UVw>? Mn[5d5VxeHKnc4Pld{Bj[XOjbDDs[ZZmdHNib3[gdIhwe3Cqb4L5cIF1cW:wIH;mJHM3KCiVMkO1M|I{PiluIETFMWJROSBqVEO3M|Q3MSxiYX7kJGFsfCBqU{S3N{khcW5iYTD0bY1mNWSncHXu[IVvfCCvYX7u[ZLDqA>? M1vpOFI{Pzl7OEWy
H1650  MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVO3[opFUUN3ME2zMlXDuTFwMjFOwG0> MX[yN|I4PDd3OB?=
HUVECs  MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIXjWmQ4OiCq NUXiNGQ5UUN3MNMgQUA4NjFizsztc4wwVA>? NUHUdXdOOjJ4MUGwNlc>
KYN-2  MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3\IVVczKGh? MnK3TWM2OMLiPTC4MlEh|ryvb3yvUC=> NIHMb|AzOjZzMUCyOy=>
HuH-7  M{jlU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUC3NkBp M4TXOWlEPTEEoE2gPU41KM7:bX;sM2w> MWqyNlYyOTB{Nx?=
HUVECs  Moe2SpVv[3Srb36gRZN{[Xl? M3GyN|EwPS9zMDFOwG0> NIX6boQyKGh? NF7udnl{cWewaX\pZ4FvfGy7IHnubIljcXS|IG\FS2ZTNTJicHjvd5Bpd3K7bHH0bY9v NE\SUJkzOjZzMUCyOy=>
HAK1-B MkL4SpVv[3Srb36gRZN{[Xl? MWCxM|UwOTBizszN MmW2NUBp MVjzeZBxemW|c3XzJGVITlJicHjvd5Bpd3K7bHH0bY9v NW\xfpV6OjJ4MUGwNlc>
UM-22A MoG4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{PyWFAuPiEQvF2= MoS3O|IhcA>? Mn\oSG1UVw>? MmLwbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NEXlTJkzOjNyN{ezOS=>
UM-22B MnLjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUiwMVYh|ryP NHPyeWg4OiCq NUfSSGdrTE2VTx?= NFHSOXRqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NGj0UY0zOjNyN{ezOS=>
PCI-37A MlK5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXKwMVYh|ryP MXO3NkBp MWTEUXNQ NH3VUHJqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NUX5XVJTOjJ|MEe3N|U>
PCI-37B M4\SO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4W0NFAuPiEQvF2= MnWyO|IhcA>? MnfOSG1UVw>? NHOxZoNqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NGLz[ZUzOjNyN{ezOS=>
PCI-15B MmHxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIPnO5oxNTZizszN NWDQWnMzPzJiaB?= MknOSG1UVw>? MoPIbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NYPFOIpPOjJ|MEe3N|U>
SCC-25 NEDFUplIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmPRNE03KM7:TR?= Ml7IO|IhcA>? M2D1XWROW09? MX\pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NH63dZgzOjNyN{ezOS=>
UM-22A M1PRfWZ2dmO2aX;uJGF{e2G7 Mnn1NE0yOCEQvF2= MXmyOEBp NIrXUGxFVVOR NWDMcJJicW6qaXLpeJMhfGinIHHjeIl3[XSrb36gc4YhfGinIFXHSnIhfHm{b4PpcoUhc2mwYYPlJIFv\CCjbIPvJIRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDv[kBxcG:|cHjvdplt[XSnZDDmc5JueyCxZjD0bIUh\G:5boP0doVidSC|aXfuZYxqdmdiZXzlcYVvfHNuIGPURXQ{KGGwZDDNRXBM Mlr2NlI{ODd5M{W=
UM-22B MlTKSpVv[3Srb36gRZN{[Xl? NH7TcmExNTFyIN88US=> M2rRb|I1KGh? NHHkcGtFVVOR NEXOfpBqdmirYnn0d{B1cGViYXP0bZZifGmxbjDv[kB1cGViRVfGVkB1gXKxc3nu[UBscW6jc3WgZY5lKGGuc3:g[IVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIH;mJJBpd3OyaH;yfYxifGWmIH\vdo1{KG:oIITo[UBld3ewc4Ty[YFuKHOrZ37hcIlv\yCnbHXt[Y51eyxiU2TBWFMh[W6mIF3BVGs> NHLTVWEzOjNyN{ezOS=>
PCI-15B MmTJSpVv[3Srb36gRZN{[Xl? Ml\DNE0yOCEQvF2= Ml3LNlQhcA>? MULEUXNQ M2jZPIlvcGmkaYTzJJRp\SCjY4TpeoF1cW:wIH;mJJRp\SCHR1\SJJR6em:|aX7lJItqdmG|ZTDhcoQh[Wy|bzDk[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ib3[gdIhwe3Cqb4L5cIF1\WRiZn;ycZMhd2ZidHjlJIRwf26|dILlZY0he2mpbnHsbY5oKGWuZX3lcpR{NCCVVFHUN{BidmRiTVHQTy=> NH:xUm0zOjNyN{ezOS=>
PCI-37A MY\GeY5kfGmxbjDBd5NigQ>? M{S0NlEh|ryP NXPuUmcyOjRiaB?= M4GzeWROW09? NF;rWlRld3ewcnXneYxifGW|IG\FS2YheHKxZIXjeIlwdg>? M2XDW|IzOzB5N{O1
UM-22A NEPSO29HfW6ldHnvckBCe3OjeR?= MVKxJO69VQ>? NFuxZ|QzPCCq NVLMfnlqTE2VTx?= MkPk[I94dnKnZ4XsZZRmeyCYRVfGJJBzd2S3Y4Tpc44> NGDmfFAzOjNyN{ezOS=>
PCI-15B M3zMV2Z2dmO2aX;uJGF{e2G7 MXyxJO69VQ>? MYCyOEBp MYTEUXNQ NVjaR5Zm\G:5boLl[5Vt[XSnczDWSWdHKHC{b3T1Z5Rqd25? MkH2NlI{ODd5M{W=
PCI-15B NEnSfWlKdn[jc3nvckBCe3OjeR?= M1HENFI1KGh? NXK2e5BFTE2VTx?= M{LESWVEPTB;NUW4JI5O NYjCbWROOjJ|MEe3N|U>
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201T  NXLTWHV[TnWwY4Tpc44hSXO|YYm= MnLQNU82NzFyIN88US=> NW\GOpZ[PDhiaB?= NGHmS2JFVVOR M{DpSYJtd2OtczD0bIUheGixc4Doc5J6dGG2aX;uJI9nKEGtdDDpcoR2[2WmIHL5JHZGT0[F M2fuRlIzOjV6NEe2
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ACCM M{D6eWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVzHdHZpOC1zMDFOwG0> NYnkcY02PzJiaB?= MYjpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M4P3c|E5Pjl6MEK1
ACC3 MkDKRZBweHSxc3nzbUBCe3OjeR?= Mk\CNE0yOCEQvF2= M3PISlczKGh? NYLs[mVTcW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> NVP0U3N{OTh4OUiwNlU>
ACC2 MofrRZBweHSxc3nzbUBCe3OjeR?= NFvIRpcxNTFyIN88US=> NVfVb5BKPzJiaB?= MVLpcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 Mor3NVg3QThyMkW=
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EHMES-10 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFrJSoc4OiCq NUfkfVZ[TE2VTx?= MWDJR|UxRTBwMzFOwG0> MXOxPFM3PDJ2OB?=
211H NWrIRY5yT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWG3NkBp NHvSZpdFVVOR NEPtNFhKSzVyPUKuNkDPxE1? MVqxPFM3PDJ2OB?=
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H2452 MmfuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV:3NkBp NE\Je5JFVVOR M3XZOmlEPTB;NT61JO69VQ>? MYCxPFM3PDJ2OB?=
CNE-1 NYfFe3hsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEfwTXkxNjFvMkWuOkDPxE1? M2\jflQ5KGh? NEfPUWpKSzVyPUOuOkDPxE1? Mn\3NVc3OzF4NE[=
CNE-2 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NInlSXoxNjFvMkWuOkDPxE1? NGjCd281QCCq MnnrTWM2OD14LkKg{txO MYixO|Y{OTZ2Nh?=
C666-1 M4m4bmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWr6WGdjOC5zLUK1MlYh|ryP NHXDeGw1QCCq NYPrRXRFUUN3ME2yN{41KM7:TR?= NFrPXmYyPzZ|MU[0Oi=>
CNE-1 NELGRZhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXewMlEuOjVwNjFOwG0> M1fQUlczKGh? MkHPTWM2OD1{LkOg{txO MVexO|Y{OTZ2Nh?=
CNE-2 NFS2[IdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlH1NE4yNTJ3Lk[g{txO MVS3NkBp NEjIflhKSzVyPUOuOkDPxE1? M1Hme|E4PjNzNkS2
C666-1 NXvnRlZoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M17pW|AvOS1{NT62JO69VQ>? NIKyR3M4OiCq M{TzXWlEPTB;ND64OkDPxE1? NW\MOY56OTd4M{G2OFY>
CNE-1 M2H3OGZ2dmO2aX;uJGF{e2G7 MlK1OkDPxE1? NYDYXGd4OjRiaB?= NIXKN5ll\WyjeYOgS|AwTzFiY3XscEBkgWOuZTDwdo9oemW|c3nvci=> NX3IZWZSOTd4M{G2OFY>
CNE-2 NYfMe5F2TnWwY4Tpc44hSXO|YYm= MoHVOkDPxE1? M2XxUFI1KGh? NYTDeZA6\GWuYYnzJGcxN0dzIHPlcIwh[3mlbHWgdJJw\3Knc4Ppc44> MVyxO|Y{OTZ2Nh?=
C666-1 NVfQe2puTnWwY4Tpc44hSXO|YYm= M4q5N|Yh|ryP MnPUNlQhcA>? MXPk[YxigXNiR{CvS|Eh[2WubDDjfYNt\SCycn;ndoV{e2mxbh?= M3S5T|E4PjNzNkS2

... Click to View More Cell Line Experimental Data

In vivo Vandetanib (2.5 mg/kg, i.v.), reverses a VEGF-induced hypotension by 63% but does not significantly affect a bFGF-induced hypotension. Vandetanib (100 mg/kg) inhibits the tumor-induced blood vessel formation by 79%. Vandetanib (12.5-100 mg/kg, orally) shows great tumor growth inhibition in human tumor xenografts including Calu-6, PC-3, MDA-MA-231, SKOV-3, SW620, A549, A431, B16-F10(AP3) and Lewis Lung, with little effects on body weight. [1] In PC3wt xenografts, administration of Vandetanib alone exerts paradoxical tumor growth stimulating effects. In PC3R xenografts, the low dose of Vandetanib (25 mg/kg) has no significant effect relative to control, whereas the high dose (50 mg/kg) significantly inhibits tumor growth compared with control. In contrast, the high-dose combination reveals a significant negative interaction between Vandetanib 50 mg/kg and docetaxel 30 mg/kg in PC3R cells. [3] In tumor-bearing mice, Vandetanib suppresses phosphorylation of VEGFR2 and EGFR in tumor tissues, significantly decreases tumor vessel density, enhances tumor cell apoptosis, suppresses tumor growth, improves survival, reduces number of intrahepatic metastases, and up-regulates VEGF, TGF-alpha and EGF in tumor tissues. Treatment with Vandetanib is not associated with serious adverse events, including ALT abnormality, bone marrow suppression or body weight loss. [4] Vandetanib treatment of nude mice bearing palpable GEO colon cancer xenografts (which are sensitive to inhibition of EGFR signaling) induces dose-dependent tumor growth inhibition. [5]

Protocol

Kinase Assay:[1]
+ Expand

Kinase inhibition:

Vandetanib is incubated with enzyme, 10 mM MnCl2, and 2 μM ATP in 96-well plates coated with a poly(Glu, Ala, Tyr) 6:3:1 random copolymer substrate. Phosphorylated tyrosine is then detected by sequential incubation with a mouse IgG anti-phosphotyrosine 4G10 antibody, a horseradish peroxidase-linked sheep antimouse immunoglobulin antibody, and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid). This methodology is adapted to examine selectivity versus tyrosine kinases associated with EGFR, PDGFRβ, Tie-2, FGFR1, c-kit, erbB2, IGF-1R, and FAK. All enzyme assays (tyrosine or serine-threonine) used appropriate ATP concentrations at or just below the respective Km (0.2–14 μM). Selectivity versus serine-threonine kinases (CDK2, AKT, and PDK1) is examined using a relevant scintillation proximity-assay (SPA) in 96-well plates. CDK2 assays contained 10 mM MnCl2, 4.5 μM ATP, 0.15 μCi of [γ-33 P]ATP/reaction, 50 mM HEPES (pH 7.5), 1 mM DTT, 0.1 mM sodium orthovanadate, 0.1 mM sodium fluoride, 10 mM sodium glycerophosphate, 1 mg/mL BSA fraction V, and a retinoblastoma substrate (part of the retinoblastoma gene, 792–928, expressed in a glutathione S-transferase expression system; 0.22 μM final concentration). Reactions are allowed to proceed at room temperature for 60 minutes before quenching for 2 hours with 150 μL of a solution containing EDTA (62 mM final concentration), 3 μg of a rabbit immunoglobulin anti-glutathione S-transferase antibody and protein A SPA-polyvinyltoluene beads (0.8 mg/reaction). Plates are then sealed, centrifuged (1200× g for 5 minutes), and counted on a Microplate scintillation counter for 30 seconds.
Cell Research:[1]
+ Expand
  • Cell lines: Calu-6, PC-3, MDA-MA-231, SKOV-3, SW620, A549, A431, B16-F10(AP3) and Lewis Lung cells
  • Concentrations: 0.1–100 μM
  • Incubation Time: 72 hours
  • Method: Tumor cells are plated in their respective media at predetermined densities that are known to enable logarithmic cell growth during the period of assay (PC-3, 500 cells/well; all others, 1000 cells/well). Plates are incubated for 24 hours (37 °C with CO2) before the addition of Vandetanib (0.1–100 μM) or vehicle (0.1% DMSO in medium). Plates are reincubated for an additional 72 hours before assessing cell proliferation by [3 H]thymidine incorporation by a beta counter.
    (Only for Reference)
Animal Research:[5]
+ Expand
  • Animal Models: Female athymic (nu/nu genotype) Swiss mice with PC-3, Calu-6, SKOV-3, and MDA-MB-231 tumors
  • Formulation: 1% (v/v) solution of polyoxyethylene
  • Dosages: 12.5 mg/kg/day, 25 mg/kg/day, 50 mg/kg/day, or 100 mg/kg/day
  • Administration: Oral administration
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 4 mg/mL (8.41 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 1% CMC Na 30mg/mL

* 1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 475.35
Formula

C22H24BrFN4O2

CAS No. 443913-73-3
Storage powder
in solvent
Synonyms N/A

Bio Calculators

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Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00514046 Active, not recruiting Medullary Thyroid Carcinoma|Multiple Endocrine Neoplasia Type 2A|Multiple Endocrine Neoplasia Type 2B National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) July 9, 2007 Phase 1|Phase 2
NCT02495103 Recruiting Renal Cell Carcinoma|Hereditary Leiomyomatosis and Renal Cell Cancer|Papillary Renal Cell Carcinoma, Sporadic National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) June 30, 2015 Phase 1|Phase 2
NCT00272350 Completed Recurrent High-Grade Gliomas|Progressive Low-Grade Gliomas|Malignant Gliomas National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) December 29, 2005 Phase 1
NCT02638428 Recruiting Relapsed Pediatric Solid Tumor|Refractory Pediatric Solid Tumor|Relapsed Pediatric AML|Refractory Pediatric AML Samsung Medical Center|Ministry of health & welfare, Republic of Korea December 2015 Phase 2
NCT02530411 Recruiting Neoplasms Velindre NHS Trust|Cancer Research UK|AstraZeneca April 2015 Phase 2
NCT02239952 Recruiting Cancer|High-grade Glioma VU University Medical Center November 2014 --

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID