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. It also inhibits VEGFR3 and EGFR with IC50 of 110 nM and 500 nM, respectively. Not sensitive to PDGFRβ, Flt1, Tie-2 and FGFR1 with IC50 of 1.1-3.6 μM. No activity against MEK, CDK2, c-Kit, erbB2, FAK, PDK1, Akt and IGF-1R with IC50 above 10 μM.

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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

Biological Activity

Description Vandetanib (ZD6474) is a potent inhibitor of VEGFR2 with IC50 of 40 nM in a cell-free assay. It also inhibits VEGFR3 and EGFR with IC50 of 110 nM and 500 nM, respectively. Not sensitive to PDGFRβ, Flt1, Tie-2 and FGFR1 with IC50 of 1.1-3.6 μM. No activity against MEK, CDK2, c-Kit, erbB2, FAK, PDK1, Akt and IGF-1R with IC50 above 10 μM.
Targets
VEGFR2 [1]
(Cell-free assay)
VEGFR3 [1] EGFR [1]
40 nM 110 nM 500 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  NH;meYhHfW6ldHnvckBCe3OjeR?= NH[wcYM2ODEkgJnuUeKh MVGxOkBp MmjLbY5kemWjc3XzJGNZS1J2IHX4dJJme3Orb36gd4lodmmoaXPhcpRtgQ>? Mmn0NlU3PzZ4OUG=
SN186 Mly2SpVv[3Srb36gRZN{[Xl? NIDj[3k2ODEkgJnuUeKh NX74bXJrOTZiaB?= NGjYeo5qdmO{ZXHz[ZMhS1iFUkSg[ZhxemW|c3nvckB{cWewaX\pZ4FvfGy7 NVfYR5poOjV4N{[2PVE>
SN179  MoTNSpVv[3Srb36gRZN{[Xl? MYK1NFDjiImwTdMg MYmxOkBp M33mZYVvcGGwY3XzJJRp\SCFWFPMNVIh\Gm{ZXP0[YQhdWmpcnH0bY9v NIn2eIMzPTZ5Nk[5NS=>
SN179  M2LOZ2Z2dmO2aX;uJGF{e2G7 NHzuSoc2ODEkgJnuUeKh M37UblE3KGh? NEPSbnlqdmO{ZXHz[ZMh[mG|YXygcYloemG2aX;uxsA> NE\4c4EzPTZ5Nk[5NS=>
Jurkat NV3TVZFMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWO3NuKhcMLi NXXpOJo{T0l3ME2xMlUhyrFiMD6yJO69VQ>? NWLrfJdFOjR4OEGyNFU>
K-562 MlfhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmjaO|LDqGkEoB?= MVvHTVUxRTFwODFCtUAxNjFizszN M3jRRlI1PjhzMkC1
NCTC-2544 NHT1dXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M336OlczyqCqwrC= NIG1Uo5IUTVyPUSuOkDDuSByLkOg{txO MYCyOFY5OTJyNR?=
A-431 NFu4SGlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX7LcWtTPzMEoHlCpC=> NYm3SWp3T0l3ME2yMlQhyrFiMD6zJO69VQ>? NVLhWG1YOjR4OEGyNFU>
SK-N-SH NWfCPWx6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFP5T2cxNjZ{NT2yNEDPxE1? MWS0PEBp MXLEUXNQ NVy1fWxJcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MXmyOFM6QTB5NB?=
SH-SY5Y NHq4d2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3fGTVAvPjJ3LUKwJO69VQ>? MVO0PEBp NHjTRo1FVVOR NX\TfnVDcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NYrDd|hmOjR|OUmwO|Q>
SK-N-SH NWLpVlVQSXCxcITvd4l{cSCDc4PhfS=> NGPsdlQ2NzFyL{KwJO69VQ>? NHvGbVE1QCCq NV\YZZJPTE2VTx?= NXXOPWcycW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> MViyOFM6QTB5NB?=
SH-SY5Y MVTBdI9xfG:|aYPpJGF{e2G7 M1f3S|UwOTBxMkCg{txO NEXEfmU1QCCq M2TwU2ROW09? M{HMUYlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= NFPCZVIzPDN7OUC3OC=>
SK-N-SH MVLGeY5kfGmxbjDBd5NigQ>? NU\vdml5PS9zMD:yNEDPxE1? M3G1eFQ5KGh? MYfEUXNQ MkW2bY5lfWOnczDHNUBxcGG|ZTDj[YxtKGO7Y3zlJIFzemW|dB?= M13J[VI1Ozl7MEe0
SH-SY5Y NEHTN|VHfW6ldHnvckBCe3OjeR?= M3OxVlUwOTBxMkCg{txO M3z5PVQ5KGh? M3j4emROW09? MmXWbY5lfWOnczDHNUBxcGG|ZTDj[YxtKGO7Y3zlJIFzemW|dB?= NEjXbGwzPDN7OUC3OC=>
SK-N-SH MojmSpVv[3Srb36gRZN{[Xl? NYTwfZliOS93L{GwJO69VQ>? NYrrUZRGPDhiaB?= NVzHPHhzTE2VTx?= NIPrOFdqdmirYnn0d{BTTVRicHjvd5Bpd3K7bHH0bY9v MWGyOFM6QTB5NB?=
SH-SY5Y MXrGeY5kfGmxbjDBd5NigQ>? MkXLNU82NzFyIN88US=> MnnsOFghcA>? NEDQT3RFVVOR NH7nXplqdmirYnn0d{BTTVRicHjvd5Bpd3K7bHH0bY9v MUmyOFM6QTB5NB?=
SK-N-SH MlnTSpVv[3Srb36gRZN{[Xl? NV3hfGlUPS9zMDFOwG0> M3XXTlQ5KGh? MnTFSG1UVw>? M2TDS4lvcGmkaYTzJIh2dWGwIF7CJINmdGxibXnndoF1cW:w M4nqWVI1Ozl7MEe0
SH-SY5Y NUO1OYpDTnWwY4Tpc44hSXO|YYm= NYK5dFI2PS9zMDFOwG0> NEfMeWE1QCCq MVrEUXNQ NGjDSmlqdmirYnn0d{BpfW2jbjDORkBk\WyuIH3p[5JifGmxbh?= M{S5OlI1Ozl7MEe0
SK-N-SH MoXiSpVv[3Srb36gRZN{[Xl? MWW1M|ExKM7:TR?= MlS5OFghcA>? M3HpTGROW09? NGXJSYpqdmirYnn0d{BpfW2jbjDORkBk\WyuIHnueoF{cW:w M1rvbVI1Ozl7MEe0
SH-SY5Y NXvsVGNKTnWwY4Tpc44hSXO|YYm= NETNVnY2NzFyIN88US=> NXr3cppmPDhiaB?= NYizdJRjTE2VTx?= MlrLbY5pcWKrdIOgbJVu[W5iTlKgZ4VtdCCrbo\hd4lwdg>? NIfJSJczPDN7OUC3OC=>
SK-N-SH NF;nW5lHfW6ldHnvckBCe3OjeR?= NYnMRWhWPSEQvF2= NG\EbpgzPC92OD:3NkBp NXTk[m1iTE2VTx?= NEP4dmJ{fXCycnXzd4V{KHSqZTDlfJBz\XO|aX;uJI9nKEO[Q2K0JIFv\CCPTWCxOEBuWk6D MoDQNlQ{QTlyN{S=
SH-SY5Y M4C2ZWZ2dmO2aX;uJGF{e2G7 NHTWNIk2KM7:TR?= MUCyOE81QC95MjDo NWmxWItvTE2VTx?= NXnpeZhHe3WycILld5NmeyC2aHWg[ZhxemW|c3nvckBw\iCFWFPSOEBidmRiTV3QNVQhdVKQQR?= MY[yOFM6QTB5NB?=
SK-N-SH MkHBSpVv[3Srb36gRZN{[Xl? NILKdZk2KM7:TR?= MoLsOFgwPzJiaB?= M1PwTmROW09? Mly1d5VxeHKnc4Pld{BmgHC{ZYPzbY9vKG:oIITo[UBEYEOUNDDhcoQhVU2SMUSgdJJwfGWrbh?= MU[yOFM6QTB5NB?=
SH-SY5Y MnHBSpVv[3Srb36gRZN{[Xl? M3fVbFUh|ryP M33ySlQ5Nzd{IHi= M3jHcGROW09? MWDzeZBxemW|c3XzJIV5eHKnc4Ppc44hd2ZidHjlJGNZS1J2IHHu[EBOVVBzNDDwdo91\Wmw MVqyOFM6QTB5NB?=
HMEpC NGnlWoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWHGUIhVOSCwTT2xNFAh|ryP MkLxOFjDqGkEoB?= NIrjcVhFVVOR MWjpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NYrOO5F{OjRzM{i4OFM>
MCF-7 M4LCS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWOxJI5ONTFyMDFOwG0> MmKwOFjDqGkEoB?= M1[x[mROW09? MYPpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> Mn;0NlQyOzh6NEO=
ZR-75-1 NHXzS5JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXSxJI5ONTFyMDFOwG0> M2fudVQ5yqCqwrC= MnrjSG1UVw>? NWW2bYd4cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NYXncXVpOjRzM{i4OFM>
MDA-MB-231 NF\1eGVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4nFd|Ehdk1vMUCwJO69VQ>? MkfXOFjDqGkEoB?= NFP0Zo9FVVOR NIf5WJNqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? Mn3RNlQyOzh6NEO=
MDA-MB-468 MkHhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NITYOXMyKG6PLUGwNEDPxE1? NGrw[ZE1QMLiaNMg NHXqWZFFVVOR NYTDW21wcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MX:yOFE{QDh2Mx?=
T-47-D M3mwNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH7jZ2YyKG6PLUGwNEDPxE1? MXq0POKhcMLi M3rGWWROW09? NVP2eJpkcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NVOyNmZpOjRzM{i4OFM>
U251  M4XydGZ2dmO2aX;uJGF{e2G7 MnqyNk81NzkkgJpOwQKFu8Li NVvZR25bPi9zMj:yOEBp NI\KPI5FVVOR NUTBR4M1cW6lcnXhd4V{KHSqZTDMR|MuUUlibHX2[YwhcW5iYTD0bY1mNWSncHXu[IVvfCCjbnSg[I9{\S2mZYDlcoRmdnRibXHucoVz M3Wyb|I{Pzl7OEWy
U87MG MXXGeY5kfGmxbjDBd5NigQ>? NILuTZQzNzRxOPMAje696oT|wrC= M{PPPVYwOTJxMkSgbC=> NILOendFVVOR M17VdYlv[3KnYYPld{B1cGViTFOzMWlKKGyndnXsJIlvKGFidHnt[U1l\XCnbnTlcpQh[W6mIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> NF:wfWgzOzd7OUi1Ni=>
U251  MkXsSpVv[3Srb36gRZN{[Xl? NEHlelU16oDLzs|iiNPDqA>? NEjLSnkzNzZxMUKgbC=> M4rncGROW09? NW\tO|hLe3WycILld5NmeyCkYYPhcEBt\X[nbIOgc4YheGixc4Doc5J6dGG2aX;uJI9nKFN4IDjTNlM2NzJ|NjmsJFRGNUKSMTCoWFM4NzR4KTygZY5lKEGtdDCoV|Q4OyliaX6gZUB1cW2nLXTldIVv\GWwdDDtZY5v\XMEoB?= NWHY[m5ZOjN5OUm4OVI>
U87MG NV71cGxbTnWwY4Tpc44hSXO|YYm= Ml:4OQKBkc7:4pUzxsA> NVuzdm5IOi94L{GyJIg> M2DFcWROW09? MlPId5VxeHKnc4Pld{Bj[XOjbDDs[ZZmdHNib3[gdIhwe3Cqb4L5cIF1cW:wIH;mJHM3KCiVMkO1M|I{PiluIETFMWJROSBqVEO3M|Q3MSxiYX7kJGFsfCBqU{S3N{khcW5iYTD0bY1mNWSncHXu[IVvfCCvYX7u[ZLDqA>? NIXXZo0zOzd7OUi1Ni=>
H1650  NGDpboJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXXJR|UxRTNwNdMxNU4zKM7:TR?= MV[yN|I4PDd3OB?=
HUVECs  M2TIR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1zacVczKGh? M3HuW2lEPTEEoE2gO{4yKM7:bX;sM2w> MlHSNlI3OTFyMke=
KYN-2  MnLMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NITvT3g4OiCq NGTU[3VKSzVywrC9JFgvOSEQvH3vcE9N MWiyNlYyOTB{Nx?=
HuH-7  MkL6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX23NkBp MofmTWM2OMLiPTC5MlQh|ryvb3yvUC=> M3HrN|IzPjFzMEK3
HUVECs  NVTnN41JTnWwY4Tpc44hSXO|YYm= M1i2UlEwPS9zMDFOwG0> NXXvZ3BNOSCq MXjzbYdvcW[rY3HueIx6KGmwaHnibZR{KF[HR1\SMVIheGixc4Doc5J6dGG2aX;u M2rnflIzPjFzMEK3
HAK1-B NUfXRYxbTnWwY4Tpc44hSXO|YYm= MnXVNU82NzFyIN88US=> MYCxJIg> NGXrPJh{fXCycnXzd4V{KEWJRmKgdIhwe3Cqb4L5cIF1cW:w NXXpWXljOjJ4MUGwNlc>
UM-22A MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoDiNE03KM7:TR?= NGHUbmI4OiCq NXnqTHVoTE2VTx?= MoPwbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MXmyNlMxPzd|NR?=
UM-22B NIf6S3hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkLkNE03KM7:TR?= NVfBR|N[PzJiaB?= NFXUVIZFVVOR NI\le4NqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M3f3[|IzOzB5N{O1
PCI-37A Ml7CS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1zqOFAuPiEQvF2= M1XyW|czKGh? NWTl[ppGTE2VTx?= Mn6ybY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> Ml\wNlI{ODd5M{W=
PCI-37B NIPvTZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIj3O3AxNTZizszN M3\GO|czKGh? M1v1VWROW09? M1LYNYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M{POd|IzOzB5N{O1
PCI-15B NVP2WXJmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{DocVAuPiEQvF2= NXTSNWlCPzJiaB?= NHTNZldFVVOR NXPxd4lkcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M{ThR|IzOzB5N{O1
SCC-25 Ml35S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn3FNE03KM7:TR?= MX[3NkBp MkPLSG1UVw>? NUHyNo9XcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NXfISVhPOjJ|MEe3N|U>
UM-22A Mne2SpVv[3Srb36gRZN{[Xl? Mle5NE0yOCEQvF2= NFHWfFYzPCCq MUfEUXNQ MXvpcohq[mm2czD0bIUh[WO2aY\heIlwdiCxZjD0bIUhTUeIUjD0fZJwe2mwZTDrbY5ie2ViYX7kJIFte29iZHXjdoVie2W|IITo[UBmgHC{ZYPzbY9vKG:oIIDoc5NxcG:{eXzheIVlKG[xcn3zJI9nKHSqZTDkc5dve3S{ZXHtJJNq\26jbHnu[{BmdGWvZX70d{whW1SDVEOgZY5lKE2DUFu= MlflNlI{ODd5M{W=
UM-22B MUfGeY5kfGmxbjDBd5NigQ>? MkDENE0yOCEQvF2= NUTISZg1OjRiaB?= NF3ySmdFVVOR MmDpbY5pcWKrdIOgeIhmKGGldHn2ZZRqd25ib3[geIhmKEWJRmKgeJlzd3OrbnWgb4lv[XOnIHHu[EBidHOxIHTlZ5Jm[XOnczD0bIUh\XiycnXzd4lwdiCxZjDwbI9{eGixconsZZRm\CCob4Ltd{Bw\iC2aHWg[I94dnO2cnXhcUB{cWewYXzpcoch\WynbXXueJMtKFOWQWSzJIFv\CCPQWDL M3WyeVIzOzB5N{O1
PCI-15B NFP2bJBHfW6ldHnvckBCe3OjeR?= NGXiW|AxNTFyIN88US=> MlPXNlQhcA>? M1jEOGROW09? MXjpcohq[mm2czD0bIUh[WO2aY\heIlwdiCxZjD0bIUhTUeIUjD0fZJwe2mwZTDrbY5ie2ViYX7kJIFte29iZHXjdoVie2W|IITo[UBmgHC{ZYPzbY9vKG:oIIDoc5NxcG:{eXzheIVlKG[xcn3zJI9nKHSqZTDkc5dve3S{ZXHtJJNq\26jbHnu[{BmdGWvZX70d{whW1SDVEOgZY5lKE2DUFu= NVXETIJ[OjJ|MEe3N|U>
PCI-37A M1HBWWZ2dmO2aX;uJGF{e2G7 MlnWNUDPxE1? M1nJelI1KGh? MX7EUXNQ NELmeWxld3ewcnXneYxifGW|IG\FS2YheHKxZIXjeIlwdg>? NWf1bpVWOjJ|MEe3N|U>
UM-22A NGHFdmNHfW6ldHnvckBCe3OjeR?= Mnf5NUDPxE1? NILxfpQzPCCq M3XqWWROW09? Mkn0[I94dnKnZ4XsZZRmeyCYRVfGJJBzd2S3Y4Tpc44> NFnrOG4zOjNyN{ezOS=>
PCI-15B NVXHWFFUTnWwY4Tpc44hSXO|YYm= M37ybFEh|ryP NFzJd24zPCCq NYPxS5gzTE2VTx?= Mmrz[I94dnKnZ4XsZZRmeyCYRVfGJJBzd2S3Y4Tpc44> MX[yNlMxPzd|NR?=
PCI-15B MYXJcpZie2mxbjDBd5NigQ>? MUmyOEBp NXqyeWZjTE2VTx?= NVKxWoZRTUN3ME21OVghdk1? NIjKPIwzOjNyN{ezOS=>
PCI-37A MmjYTY53[XOrb36gRZN{[Xl? M{f3flI1KGh? MXvEUXNQ MU\FR|UxRTF4OUWgcm0> Mn3QNlI{ODd5M{W=
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201T  NFjFWJBHfW6ldHnvckBCe3OjeR?= NELMTZIyNzVxMUCg{txO NEH6Opg1QCCq NHP5eWNFVVOR MmLmZoxw[2u|IITo[UBxcG:|cHjvdplt[XSrb36gc4YhSWu2IHnu[JVk\WRiYomgWmVITkN? Mm[xNlIzPTh2N{[=
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ACC2 NH3RbZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUfwT4RKOC1zMDFOwG0> MVu3NkBp MkO2bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NHLDT2UyQDZ7OECyOS=>
ACCM Ml\GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MW[wMVExKM7:TR?= MVq3NkBp MnexbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MWCxPFY6QDB{NR?=
ACC3 NV;NcGJJSXCxcITvd4l{cSCDc4PhfS=> NUDhTmx7OC1zMDFOwG0> NEjQZXg4OiCq NFjze4ZqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 Mn\CNVg3QThyMkW=
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EHMES-1 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH7xWG44OiCq MmPRSG1UVw>? MoLPTWM2OD1zMD62JO69VQ>? Mn7CNVg{PjR{NEi=
EHMES-10 Mo\5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2\0WVczKGh? MVHEUXNQ NUPq[W9wUUN3ME2wMlMh|ryP M2izWFE5OzZ2MkS4
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H2452 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NICyTZU4OiCq Mke2SG1UVw>? NYK1NXNbUUN3ME21MlUh|ryP NEnaZpYyQDN4NEK0PC=>
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CNE-2 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX7xOphoOC5zLUK1MlYh|ryP NH\OU3g1QCCq NVv0[W1FUUN3ME22MlIh|ryP MV:xO|Y{OTZ2Nh?=
C666-1 M2XlUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHzZN|IxNjFvMkWuOkDPxE1? M3jmPFQ5KGh? M3G1R2lEPTB;MkOuOEDPxE1? MlS4NVc3OzF4NE[=
CNE-1 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkD0NE4yNTJ3Lk[g{txO NGrZdHY4OiCq MmfPTWM2OD1{LkOg{txO M3;vUFE4PjNzNkS2
CNE-2 MlrSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MknvNE4yNTJ3Lk[g{txO NWm4WYFTPzJiaB?= NX;lU3FnUUN3ME2zMlYh|ryP NVzPdYlCOTd4M{G2OFY>
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CNE-1 M13xPWZ2dmO2aX;uJGF{e2G7 NVHGdXdiPiEQvF2= MlvTNlQhcA>? Mmnh[IVt[Xm|IFewM2cyKGOnbHygZ5lkdGVicILv[5Jme3Orb36= M{TqXlE4PjNzNkS2
CNE-2 NEi4d3BHfW6ldHnvckBCe3OjeR?= NV7jdVl2PiEQvF2= MXyyOEBp NYH6fo1U\GWuYYnzJGcxN0dzIHPlcIwh[3mlbHWgdJJw\3Knc4Ppc44> NGDoWnMyPzZ|MU[0Oi=>
C666-1 MWXGeY5kfGmxbjDBd5NigQ>? M4T6OVYh|ryP Mof3NlQhcA>? MXLk[YxigXNiR{CvS|Eh[2WubDDjfYNt\SCycn;ndoV{e2mxbh?= MYSxO|Y{OTZ2Nh?=

... 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

Molarity Calculator

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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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Calculate the dilution required to prepare a stock solution. The Selleck dilution 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