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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7 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.

  • (H) Anti-pSTAT3Y705, total STAT3, pSRCy416 of RWPE-1 transfectants treated for 6 hours with vandetanib at the indicated concentrations. Actin was used as loading control.

    J Cancer, 2017, 8(1):140-145. Vandetanib (ZD6474) purchased from Selleck.

    LS-007 inhibits CDK1/CDK7/CDK9 activity in AL cells. HL-60 (A), CCRF-CEM (B) cells were treated with increasing concentrations of LS-007 or flavopiridol for 2 h, and cell lysates were collected and examined by immunoblotting with the indicated antibodies.

    Acta Pharmacol Sin, 2016, 37(11):1481-1489. 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  M4frcmZ2dmO2aX;uJGF{e2G7 NXzhe5R7PTBy4pEJcm3DqA>? NWD2bIU4OTZiaB?= MUXpcoNz\WG|ZYOgR3hEWjRiZYjwdoV{e2mxbjDzbYdvcW[rY3HueIx6 MW[yOVY4PjZ7MR?=
SN186 Mn\JSpVv[3Srb36gRZN{[Xl? MUK1NFDjiImwTdMg NGnzUGUyPiCq MXnpcoNz\WG|ZYOgR3hEWjRiZYjwdoV{e2mxbjDzbYdvcW[rY3HueIx6 M131dVI2Pjd4Nkmx
SN179  MlziSpVv[3Srb36gRZN{[Xl? MXW1NFDjiImwTdMg MkjONVYhcA>? NX;o[Ytb\W6qYX7j[ZMhfGinIFPYR2wyOiCmaYLlZ5Rm\CCvaXfyZZRqd25? M3jsfVI2Pjd4Nkmx
SN179  M1TLdmZ2dmO2aX;uJGF{e2G7 NEf3S4E2ODEkgJnuUeKh MoDSNVYhcA>? Ml3GbY5kemWjc3XzJIJie2GuIH3p[5JifGmxbtMg M1jWXlI2Pjd4Nkmx
Jurkat MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2W3SFczyqCqwrC= NFS2WJBIUTVyPUGuOUDDuSByLkKg{txO MXOyOFY5OTJyNR?=
K-562 MoPGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWHCcphpPzMEoHlCpC=> NXHKU5FVT0l3ME2xMlghyrFiMD6xJO69VQ>? NUD6TlhMOjR4OEGyNFU>
NCTC-2544 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NILFdVY4OsLiaNMg MXXHTVUxRTRwNjFCtUAxNjNizszN MUOyOFY5OTJyNR?=
A-431 NYCzWVdXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3\4VlczyqCqwrC= MnrOS2k2OD1{LkSgxtEhOC5|IN88US=> M4W5c|I1PjhzMkC1
SK-N-SH NIjaUVFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2DpT|AvPjJ3LUKwJO69VQ>? MX:0PEBp MULEUXNQ M1raV4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MlP1NlQ{QTlyN{S=
SH-SY5Y MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXXEZY53OC54MkWtNlAh|ryP MX60PEBp NXHRZ3NyTE2VTx?= NF;2NJlqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M33MXFI1Ozl7MEe0
SK-N-SH NYLFbld1SXCxcITvd4l{cSCDc4PhfS=> M1nidFUwOTBxMkCg{txO NHq2UYU1QCCq MoDoSG1UVw>? NHvWU3BqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 M3:yb|I1Ozl7MEe0
SH-SY5Y MlL6RZBweHSxc3nzbUBCe3OjeR?= NVfjbnBEPS9zMD:yNEDPxE1? MX[0PEBp MWfEUXNQ NEOwU4xqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 NF:4WYwzPDN7OUC3OC=>
SK-N-SH MWjGeY5kfGmxbjDBd5NigQ>? M{nsXVUwOTBxMkCg{txO MUi0PEBp MorqSG1UVw>? M{D1[olv\HWlZYOgS|EheGijc3WgZ4VtdCCleXPs[UBienKnc4S= NY\Qe2JoOjR|OUmwO|Q>
SH-SY5Y Ml\1SpVv[3Srb36gRZN{[Xl? NWrCPXk4PS9zMD:yNEDPxE1? MYW0PEBp NYj6bY5ETE2VTx?= MWjpcoR2[2W|IFexJJBp[XOnIHPlcIwh[3mlbHWgZZJz\XO2 M2roSVI1Ozl7MEe0
SK-N-SH Mo\XSpVv[3Srb36gRZN{[Xl? Mn7tNU82NzFyIN88US=> MYq0PEBp NE\sdIJFVVOR M{X2SolvcGmkaYTzJHJGXCCyaH;zdIhwenmuYYTpc44> NEnzfmkzPDN7OUC3OC=>
SH-SY5Y NYKwVGd{TnWwY4Tpc44hSXO|YYm= M{XKVlEwPS9zMDFOwG0> MnHEOFghcA>? NYm2epc{TE2VTx?= M3H4dolvcGmkaYTzJHJGXCCyaH;zdIhwenmuYYTpc44> M{TpVVI1Ozl7MEe0
SK-N-SH NYHDZpVlTnWwY4Tpc44hSXO|YYm= NYL3XIN2PS9zMDFOwG0> M3LQRVQ5KGh? MorPSG1UVw>? M2[0folvcGmkaYTzJIh2dWGwIF7CJINmdGxibXnndoF1cW:w NGjxfI4zPDN7OUC3OC=>
SH-SY5Y MX;GeY5kfGmxbjDBd5NigQ>? NGf4cZg2NzFyIN88US=> NE\XcpY1QCCq NYXuPFRRTE2VTx?= M{jmbYlvcGmkaYTzJIh2dWGwIF7CJINmdGxibXnndoF1cW:w MXqyOFM6QTB5NB?=
SK-N-SH NIXve41HfW6ldHnvckBCe3OjeR?= MVK1M|ExKM7:TR?= NWLCcINGPDhiaB?= MnnaSG1UVw>? MleybY5pcWKrdIOgbJVu[W5iTlKgZ4VtdCCrbo\hd4lwdg>? Ml\sNlQ{QTlyN{S=
SH-SY5Y NI[zfI1HfW6ldHnvckBCe3OjeR?= NIKxWJY2NzFyIN88US=> NHLhTHc1QCCq MoHySG1UVw>? MmXxbY5pcWKrdIOgbJVu[W5iTlKgZ4VtdCCrbo\hd4lwdg>? NF3Sc3AzPDN7OUC3OC=>
SK-N-SH M2\RW2Z2dmO2aX;uJGF{e2G7 NHyxTYo2KM7:TR?= Mmj3NlQwPDhxN{KgbC=> M1LzXWROW09? Mnrkd5VxeHKnc4Pld{B1cGViZYjwdoV{e2mxbjDv[kBEYEOUNDDhcoQhVU2SMUSgcXJPSQ>? NV7FWG1vOjR|OUmwO|Q>
SH-SY5Y MoHhSpVv[3Srb36gRZN{[Xl? NXX0VlhkPSEQvF2= NInjN48zPC92OD:3NkBp M{HLXmROW09? MnPCd5VxeHKnc4Pld{B1cGViZYjwdoV{e2mxbjDv[kBEYEOUNDDhcoQhVU2SMUSgcXJPSQ>? MlrXNlQ{QTlyN{S=
SK-N-SH MkftSpVv[3Srb36gRZN{[Xl? MUS1JO69VQ>? MnrYOFgwPzJiaB?= Mn\rSG1UVw>? NWTCcIxOe3WycILld5NmeyCneIDy[ZN{cW:wIH;mJJRp\SCFWFPSOEBidmRiTV3QNVQheHKxdHXpci=> NULXN3BYOjR|OUmwO|Q>
SH-SY5Y M2HDRmZ2dmO2aX;uJGF{e2G7 Mo\uOUDPxE1? NYq4TXF1PDhxN{KgbC=> M4fvV2ROW09? Mn\pd5VxeHKnc4Pld{BmgHC{ZYPzbY9vKG:oIITo[UBEYEOUNDDhcoQhVU2SMUSgdJJwfGWrbh?= M1zzOlI1Ozl7MEe0
HMEpC M{Hse2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFqzepgyKG6PLUGwNEDPxE1? NGTaW3c1QMLiaNMg NXG1[XAzTE2VTx?= M3H5[IlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NVfzRoZbOjRzM{i4OFM>
MCF-7 NYTwVm15T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1S2ZVEhdk1vMUCwJO69VQ>? NVPITI1HPDkEoHlCpC=> NHfNdW1FVVOR M1XoWIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NGrtd2szPDF|OEi0Ny=>
ZR-75-1 MnXlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnLXNUBvVS1zMECg{txO NYrB[GtIPDkEoHlCpC=> NFO1eWdFVVOR MUHpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MVmyOFE{QDh2Mx?=
MDA-MB-231 MlTXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2\IZlEhdk1vMUCwJO69VQ>? NFnFdZg1QMLiaNMg NXfYTmV7TE2VTx?= M4TOSolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NGHtS3czPDF|OEi0Ny=>
MDA-MB-468 NXvCOHltT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3eyO|Ehdk1vMUCwJO69VQ>? MV[0POKhcMLi NVjvb5hYTE2VTx?= MkXXbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MYCyOFE{QDh2Mx?=
T-47-D NYLa[4xpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{T6O|Ehdk1vMUCwJO69VQ>? MY[0POKhcMLi NIrnTmpFVVOR MnPubY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NFfjU3QzPDF|OEi0Ny=>
U251  M4PrN2Z2dmO2aX;uJGF{e2G7 MlH0Nk81NzkkgJpOwQKFu8Li NYW3WVRSPi9zMj:yOEBp M{fOe2ROW09? MYjpcoNz\WG|ZYOgeIhmKEyFMz3JTUBt\X[nbDDpckBiKHSrbXWt[IVx\W6mZX70JIFv\CCmb4PlMYRmeGWwZHXueEBu[W6wZYK= NWDXW3NLOjN5OUm4OVI>
U87MG MUDGeY5kfGmxbjDBd5NigQ>? NYKyR2VnOi92L{lihKnPxOLGs9Mg MX:2M|EzNzJ2IHi= NXG4T4s5TE2VTx?= NVzPO2V5cW6lcnXhd4V{KHSqZTDMR|MuUUlibHX2[YwhcW5iYTD0bY1mNWSncHXu[IVvfCCjbnSg[I9{\S2mZYDlcoRmdnRibXHucoVz M2rhXFI{Pzl7OEWy
U251  M{K5[mZ2dmO2aX;uJGF{e2G7 NVr3Z3dCPOLCid885qS{yqB? M1LmOVIwPi9zMjDo NFfoTo9FVVOR M4XCN5N2eHC{ZYPz[ZMh[mG|YXygcIV3\Wy|IH;mJJBpd3OyaH;yfYxifGmxbjDv[kBUPiBqU{KzOU8zOzZrLDC0SU1DWDFiKGSzO{81PiluIHHu[EBCc3RiKGO0O|MqKGmwIHGgeIlu\S2mZYDlcoRmdnRibXHucoVzyqB? NVfyXXZYOjN5OUm4OVI>
U87MG MnnoSpVv[3Srb36gRZN{[Xl? MUC05qCK|r{khMRCpC=> MojCNk83NzF{IHi= NWX6O5pQTE2VTx?= NX\YZm9Je3WycILld5NmeyCkYYPhcEBt\X[nbIOgc4YheGixc4Doc5J6dGG2aX;uJI9nKFN4IDjTNlM2NzJ|NjmsJFRGNUKSMTCoWFM4NzR4KTygZY5lKEGtdDCoV|Q4OyliaX6gZUB1cW2nLXTldIVv\GWwdDDtZY5v\XMEoB?= MnrvNlM4QTl6NUK=
H1650  M2Pofmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGTTRmRKSzVyPUOuOeKyOS5{IN88US=> NIPtN|czOzJ5NEe1PC=>
HUVECs  NFPVT|VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mkn0O|IhcA>? MYDJR|UxyqB;IEeuNUDPxG2xbD;M M4fMelIzPjFzMEK3
KYN-2  NXTQOnNGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYO3NkBp NEHTS49KSzVywrC9JFgvOSEQvH3vcE9N MlGxNlI3OTFyMke=
HuH-7  MnewS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYW3NkBp M4Dpc2lEPTEEoE2gPU41KM7:bX;sM2w> NHr3SXkzOjZzMUCyOy=>
HUVECs  NHrWcWtHfW6ldHnvckBCe3OjeR?= NFfafIEyNzVxMUCg{txO NIS1S5MyKGh? MVnzbYdvcW[rY3HueIx6KGmwaHnibZR{KF[HR1\SMVIheGixc4Doc5J6dGG2aX;u MX:yNlYyOTB{Nx?=
HAK1-B MnzNSpVv[3Srb36gRZN{[Xl? M3POSFEwPS9zMDFOwG0> NXLH[2VjOSCq MoT2d5VxeHKnc4Pld{BGT0[UIIDoc5NxcG:{eXzheIlwdg>? NGXwO5QzOjZzMUCyOy=>
UM-22A MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXvXcXNwOC14IN88US=> MVO3NkBp M4ri[WROW09? MXLpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NIPld44zOjNyN{ezOS=>
UM-22B NHe3XY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVL0[25OOC14IN88US=> NEDGeYI4OiCq M1HhfWROW09? NHX2SmxqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NHnJbYIzOjNyN{ezOS=>
PCI-37A MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoPBNE03KM7:TR?= MVy3NkBp MXTEUXNQ NF71[4FqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? Mny4NlI{ODd5M{W=
PCI-37B MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUmwMVYh|ryP NWrrSosxPzJiaB?= NGizN2ZFVVOR NWPSTFhocW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NGLpRpQzOjNyN{ezOS=>
PCI-15B NUDIUXFRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1zWO|AuPiEQvF2= MW[3NkBp NEXl[4FFVVOR MUHpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NViycYwyOjJ|MEe3N|U>
SCC-25 M1ThZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYrHSXZbOC14IN88US=> NWfsTmtJPzJiaB?= MmnkSG1UVw>? MnjSbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NEHweVgzOjNyN{ezOS=>
UM-22A NH63S2hHfW6ldHnvckBCe3OjeR?= MnKwNE0yOCEQvF2= M{fkclI1KGh? M1HndWROW09? MkL0bY5pcWKrdIOgeIhmKGGldHn2ZZRqd25ib3[geIhmKEWJRmKgeJlzd3OrbnWgb4lv[XOnIHHu[EBidHOxIHTlZ5Jm[XOnczD0bIUh\XiycnXzd4lwdiCxZjDwbI9{eGixconsZZRm\CCob4Ltd{Bw\iC2aHWg[I94dnO2cnXhcUB{cWewYXzpcoch\WynbXXueJMtKFOWQWSzJIFv\CCPQWDL M3mxSVIzOzB5N{O1
UM-22B M{frOGZ2dmO2aX;uJGF{e2G7 MlHLNE0yOCEQvF2= M3fUPFI1KGh? NX:xfXhPTE2VTx?= NUTxN2lzcW6qaXLpeJMhfGinIHHjeIl3[XSrb36gc4YhfGinIFXHSnIhfHm{b4PpcoUhc2mwYYPlJIFv\CCjbIPvJIRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDv[kBxcG:|cHjvdplt[XSnZDDmc5JueyCxZjD0bIUh\G:5boP0doVidSC|aXfuZYxqdmdiZXzlcYVvfHNuIGPURXQ{KGGwZDDNRXBM Mlu3NlI{ODd5M{W=
PCI-15B MlP6SpVv[3Srb36gRZN{[Xl? NFHDOFYxNTFyIN88US=> NXPHfGlxOjRiaB?= M2XSS2ROW09? NHfuZ|dqdmirYnn0d{B1cGViYXP0bZZifGmxbjDv[kB1cGViRVfGVkB1gXKxc3nu[UBscW6jc3WgZY5lKGGuc3:g[IVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIH;mJJBpd3OyaH;yfYxifGWmIH\vdo1{KG:oIITo[UBld3ewc4Ty[YFuKHOrZ37hcIlv\yCnbHXt[Y51eyxiU2TBWFMh[W6mIF3BVGs> NXrHcm41OjJ|MEe3N|U>
PCI-37A MYjGeY5kfGmxbjDBd5NigQ>? NYrhZoU5OSEQvF2= NGXLUHozPCCq M{\sS2ROW09? MkPq[I94dnKnZ4XsZZRmeyCYRVfGJJBzd2S3Y4Tpc44> NHy5W4UzOjNyN{ezOS=>
UM-22A NH;6ZlRHfW6ldHnvckBCe3OjeR?= M1Lu[FEh|ryP MWSyOEBp NEe2V4VFVVOR NEn1fm9ld3ewcnXneYxifGW|IG\FS2YheHKxZIXjeIlwdg>? NVv0SmNTOjJ|MEe3N|U>
PCI-15B M2DrfWZ2dmO2aX;uJGF{e2G7 NFfFcGsyKM7:TR?= MnS0NlQhcA>? NIHvNVRFVVOR NFPmeHBld3ewcnXneYxifGW|IG\FS2YheHKxZIXjeIlwdg>? NF3JSZYzOjNyN{ezOS=>
PCI-15B MYDJcpZie2mxbjDBd5NigQ>? MnyzNlQhcA>? NYj3UGYyTE2VTx?= NW\6TGRoTUN3ME21OVghdk1? MUmyNlMxPzd|NR?=
PCI-37A M4KwV2lvfmG|aX;uJGF{e2G7 MnniNlQhcA>? M1PQTmROW09? M{ja[mVEPTB;MU[5OUBvVQ>? NGnGfW4zOjNyN{ezOS=>
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UM-22B NXvFPXlNUW64YYPpc44hSXO|YYm= NEHCNWYzPCCq NYPUT2hyTE2VTx?= MV3FR|UxRTJ2MkSgcm0> NIG4SY0zOjNyN{ezOS=>
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201T MVHGeY5kfGmxbjDBd5NigQ>? M2TSRVIvPSEQvF2= NHXY[Jg1QCCq NYn5d4RkTE2VTx?= MXXpcohq[mm2czDwbI9{eGixLV3BVGsh\m:ubH;3bY5oKEWJRh?= MVGyNlI2QDR5Nh?=
273T  NFXUWHlHfW6ldHnvckBCe3OjeR?= NFXyNlkzNjVizszN M1v4WlQ5KGh? MmizSG1UVw>? NXfx[W5OcW6qaXLpeJMheGixc4Doc{1OSVCNIH\vcIxwf2mwZzDFS2Y> MU[yNlI2QDR5Nh?=
A549 NVHxSmpiTnWwY4Tpc44hSXO|YYm= MYKyMlUh|ryP NF7kUIw1QCCq M3fUV2ROW09? M4XETYlvcGmkaYTzJJBpd3OyaH:tUWFRUyCob3zsc5dqdmdiRVfG MlXLNlIzPTh2N{[=
201T  NHHvUGFHfW6ldHnvckBCe3OjeR?= MVOxM|UwOTBizszN NFz1T2E1QCCq MYnEUXNQ MlnjZoxw[2u|IITo[UBxcG:|cHjvdplt[XSrb36gc4YhSWu2IHnu[JVk\WRiYomgWmVITkN? NFrVXIIzOjJ3OES3Oi=>
H2052 MnPSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3jEWmlEPTB;MT6wO:KyOC5yNDFOwG0> MlToNlE6PzB6N{S=
H2452 MnTZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnLMTWM2OD1|LkWyxtEyNjF|IN88US=> M3K1blIyQTdyOEe0
H28 Mk[1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVO2V5VtUUN3ME2wMlMzyrFyLkC3JO69VQ>? MkDjNlE6PzB6N{S=
MSTO-211H NWLUcmlTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3T3U2lEPTB;MT60NuKyOC5yMzFOwG0> NUPueWFnOjF7N{C4O|Q>
Hth83 NFvteZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{\h[VczKGh? NIXRTGNFVVOR NULqdoU1UUN3ME2zMlMxKMLzIECuOlYh|ryP MmD3NlEzOjB2N{e=
C643 MnnzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUS3NkBp M4rNdGROW09? NWG0UVNWUUN3ME2zMlY2KMLzIEGuNlIh|ryP NY\SO|lxOjF{MkC0O|c>
8505C MneyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmPEO|IhcA>? MmPYSG1UVw>? NFfQSZlKSzVyPUeuOVYhyrFiMT6xN{DPxE1? M2qxWVIyOjJyNEe3
Hth74 NXriNWE4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnfTO|IhcA>? M3yxfWROW09? NYPXe|BSUUN3ME24MlU3KMLzIEGuNFEh|ryP NXvoNo85OjF{MkC0O|c>
SW1736 M1PJ[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIXMclI4OiCq NXvxU3FCTE2VTx?= NI\mRVNKSzVyPUmuNFUhyrFiMD61OUDPxE1? NWDs[nJEOjF{MkC0O|c>
Hth7 MoPUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV\MSG8zPzJiaB?= M{K5PGROW09? MXrJR|UxRTlwNk[gxtEhOC5|ODFOwG0> MX6yNVIzODR5Nx?=
Hth104 M1L1V2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF7HZ|Q4OiCq NE\IW2dFVVOR NVrudXM2UUN3ME5CtVE3Njl6INMxJG5CKM7:TR?= MWSyNVIzODR5Nx?=
HTB3 NFrx[odIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmLjNE0zOCEQvF2= MUCyOOKhcA>? MlTHbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MoTCNVkzOjB{NU[=
HT1376 Mlf5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXiwMVIxKM7:TR?= NHrxZYczPMLiaB?= NW[yc5RwcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NGm5epgyQTJ{MEK1Oi=>
RT4 NEDrZnNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIHtO4MxNTJyIN88US=> NGTMemwzPMLiaB?= NH;BcoZqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MXuxPVIzODJ3Nh?=
J82 M{LMUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX:wMVIxKM7:TR?= MUWyOOKhcA>? MWjpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M4jFUlE6OjJyMkW2
CRL1749 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHn4bHUxNTJyIN88US=> MV:yOOKhcA>? MUjpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MYCxPVIzODJ3Nh?=
T24 NIexVotIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIjSdWUxNTJyIN88US=> M1XKd|I1yqCq NWTSVI4zcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? Ml:wNVkzOjB{NU[=
SUP MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYfMRlVbOC1{MDFOwG0> MWWyOOKhcA>? MWjpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> Ml\yNVkzOjB{NU[=
HTB9 NX7WfoV[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYnFO|dsOC1{MDFOwG0> NIThcFkzPMLiaB?= MWPpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NIDSZY8yQTJ{MEK1Oi=>
ACC3 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnrTNE0yOCEQvF2= NE\6dXY4OiCq M1THeolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M{jEUlE5Pjl6MEK1
ACC2 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX7tcWt[OC1zMDFOwG0> M3O4O|czKGh? NIfITGxqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NH[0WlIyQDZ7OECyOS=>
ACCM MnrvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXewMVExKM7:TR?= M2f0NFczKGh? MWTpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NVrmenpJOTh4OUiwNlU>
ACC3 MnjnRZBweHSxc3nzbUBCe3OjeR?= MnOxNE0yOCEQvF2= Mn;LO|IhcA>? MmnPbY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= MVSxPFY6QDB{NR?=
ACC2 MoLuRZBweHSxc3nzbUBCe3OjeR?= MXOwMVExKM7:TR?= NFnIWnU4OiCq MYfpcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 NWTQXGYzOTh4OUiwNlU>
ACCM M1;q[GFxd3C2b4Ppd4khSXO|YYm= Mo\DNE0yOCEQvF2= M371S|czKGh? MX3pcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 NIHDNHkyQDZ7OECyOS=>
EHMES-1 Mm[1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NED4O5U4OiCq MnX3SG1UVw>? NHjUOplKSzVyPUGwMlYh|ryP NI\5SHYyQDN4NEK0PC=>
EHMES-10 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVe3NkBp NVvxSo03TE2VTx?= NHTSTJFKSzVyPUCuN{DPxE1? M3ftNlE5OzZ2MkS4
211H NWnjRmZMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHfa[m84OiCq MXLEUXNQ MX;JR|UxRTJwMjFOwG0> NFLHWnAyQDN4NEK0PC=>
H28 NVHyTohvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4j3[VczKGh? MWnEUXNQ Mk\mTWM2OD1zLkig{txO NXXKbnp6OTh|NkSyOFg>
H2052 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYe3NkBp MVrEUXNQ NVvwNGZpUUN3ME24MlAh|ryP NUHtcZZwOTh|NkSyOFg>
H2452 NFvuUGhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV[3NkBp M4HFOGROW09? MoPCTWM2OD13LkWg{txO MlrFNVg{PjR{NEi=
CNE-1 M2f0Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUOwMlEuOjVwNjFOwG0> NFf3dnE1QCCq Mn;RTWM2OD1|Lk[g{txO NIPwWVkyPzZ|MU[0Oi=>
CNE-2 MkK1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV6wMlEuOjVwNjFOwG0> NHr1V|U1QCCq MX\JR|UxRTZwMjFOwG0> NYX4[ZUxOTd4M{G2OFY>
C666-1 NXnzeXB[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NW\pb3dEOC5zLUK1MlYh|ryP M2rhclQ5KGh? M4KwZmlEPTB;MkOuOEDPxE1? M1T6VVE4PjNzNkS2
CNE-1 MkP5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUThVYZsOC5zLUK1MlYh|ryP NH7XcIM4OiCq MX3JR|UxRTJwMzFOwG0> NFHHO|MyPzZ|MU[0Oi=>
CNE-2 NXTCZoZmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NILWcW0xNjFvMkWuOkDPxE1? NUT5NlBQPzJiaB?= NHHHW2dKSzVyPUOuOkDPxE1? MkTlNVc3OzF4NE[=
C666-1 M{jOUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{LoT|AvOS1{NT62JO69VQ>? MWW3NkBp MljPTWM2OD12Lki2JO69VQ>? NVjSWZN[OTd4M{G2OFY>
CNE-1 M2PMe2Z2dmO2aX;uJGF{e2G7 M{LL[|Yh|ryP MmXxNlQhcA>? M1S3V4RmdGG7czDHNE9IOSClZXzsJIN6[2ynIIDyc4dz\XO|aX;u MkTlNVc3OzF4NE[=
CNE-2 NV6ySG4xTnWwY4Tpc44hSXO|YYm= MVO2JO69VQ>? MV2yOEBp MXHk[YxigXNiR{CvS|Eh[2WubDDjfYNt\SCycn;ndoV{e2mxbh?= NV3FWnI1OTd4M{G2OFY>
C666-1 NHXWPJdHfW6ldHnvckBCe3OjeR?= MVG2JO69VQ>? NXn4VZRlOjRiaB?= NVTHXW8{\GWuYYnzJGcxN0dzIHPlcIwh[3mlbHWgdJJw\3Knc4Ppc44> MUKxO|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 slightly soluble or insoluble
Ethanol slightly soluble or insoluble
In vivo Add solvents individually and in order:
1% CMC Na
30mg/mL

* 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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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.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID