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

  • (A) Representative in vivo bioluminescence of mice at and during time of treatment. Derived cell lines with either BCR-ABL1 WT or V299L was tail-vein injected into immunocompetent recipient mice. Initial imaging was performed at day 10 post-transplantation. Mice were subsequently treated once daily with vehicle, 10 mg/kg dasatinib, 50 mg/kg imatinib, 50 mg/kg vandetanib, or 50 mg/kg foretinib.
    (B) Fold change in total whole-mouse bioluminescence signal between post- and pre-treatment. Mice bearing BCR-ABL1 V299L ALLs showed significant tumor burden reduction upon treatment with foretinib or vandetanib. Statistical significance determined by Mann-Whitney test. *p < 0.05, **p < 0.01.

    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]
(Cell-free assay)
EGFR [1]
(Cell-free assay)
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  NVHtR45RTnWwY4Tpc44hSXO|YYm= MmnrOVAx6oDLbl5CpC=> M1rxRVE3KGh? NGjhWZRqdmO{ZXHz[ZMhS1iFUkSg[ZhxemW|c3nvckB{cWewaX\pZ4FvfGy7 M2S3fVI2Pjd4Nkmx
SN186 NFu5U21HfW6ldHnvckBCe3OjeR?= MWG1NFDjiImwTdMg NUnrOYFZOTZiaB?= NETMUFdqdmO{ZXHz[ZMhS1iFUkSg[ZhxemW|c3nvckB{cWewaX\pZ4FvfGy7 NWPQbpBoOjV4N{[2PVE>
SN179  Ml3VSpVv[3Srb36gRZN{[Xl? MV[1NFDjiImwTdMg NE\UdlEyPiCq NW\HcoNS\W6qYX7j[ZMhfGinIFPYR2wyOiCmaYLlZ5Rm\CCvaXfyZZRqd25? MVGyOVY4PjZ7MR?=
SN179  NFnx[2dHfW6ldHnvckBCe3OjeR?= NY\WPYlkPTBy4pEJcm3DqA>? NF7VXI8yPiCq MlrHbY5kemWjc3XzJIJie2GuIH3p[5JifGmxbtMg MlnJNlU3PzZ4OUG=
Jurkat M{nOV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{LRR|czyqCqwrC= M4e3NWdKPTB;MT61JOKyKDBwMjFOwG0> NHr1dpczPDZ6MUKwOS=>
K-562 M4PoTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUHJVHZsPzMEoHlCpC=> M3jjeGdKPTB;MT64JOKyKDBwMTFOwG0> NWS3U|RzOjR4OEGyNFU>
NCTC-2544 NI\0UplIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWG0XWZPPzMEoHlCpC=> M{fENGdKPTB;ND62JOKyKDBwMzFOwG0> M{XJVlI1PjhzMkC1
A-431 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2LlUFczyqCqwrC= MVzHTVUxRTJwNDFCtUAxNjNizszN MlH0NlQ3QDF{MEW=
SK-N-SH MmfTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFrpU3AxNjZ{NT2yNEDPxE1? MkTQOFghcA>? NEjXVFJFVVOR NIfPNG1qdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M3\PO|I1Ozl7MEe0
SH-SY5Y NF3mZmdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmPsNE43OjVvMkCg{txO MVe0PEBp M1PkWmROW09? MULpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M4\YVVI1Ozl7MEe0
SK-N-SH NYPTdZlxSXCxcITvd4l{cSCDc4PhfS=> NVLkUYJmPS9zMD:yNEDPxE1? MkTMOFghcA>? MXnEUXNQ NFrT[21qdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 NWO0UVRFOjR|OUmwO|Q>
SH-SY5Y MYnBdI9xfG:|aYPpJGF{e2G7 NF7xemg2NzFyL{KwJO69VQ>? NGDkTmM1QCCq NFfCUlRFVVOR MW\pcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 MVqyOFM6QTB5NB?=
SK-N-SH NUD4c|RETnWwY4Tpc44hSXO|YYm= MUK1M|ExNzJyIN88US=> NV\wSG03PDhiaB?= NH3E[XVFVVOR M3T2WIlv\HWlZYOgS|EheGijc3WgZ4VtdCCleXPs[UBienKnc4S= NG\0OVUzPDN7OUC3OC=>
SH-SY5Y MnHYSpVv[3Srb36gRZN{[Xl? Mk\GOU8yOC9{MDFOwG0> M{L6Z|Q5KGh? NX3W[ppnTE2VTx?= M{XiPIlv\HWlZYOgS|EheGijc3WgZ4VtdCCleXPs[UBienKnc4S= NHTmOYMzPDN7OUC3OC=>
SK-N-SH NVnJO2pQTnWwY4Tpc44hSXO|YYm= M1jOVFEwPS9zMDFOwG0> NF7uU4k1QCCq NUPXc3ZiTE2VTx?= Mnu1bY5pcWKrdIOgVmVVKHCqb4PwbI9zgWyjdHnvci=> NWKwfFQ5OjR|OUmwO|Q>
SH-SY5Y MkeySpVv[3Srb36gRZN{[Xl? M2TWSlEwPS9zMDFOwG0> MmC1OFghcA>? M1vFUmROW09? MnfRbY5pcWKrdIOgVmVVKHCqb4PwbI9zgWyjdHnvci=> M{\C[lI1Ozl7MEe0
SK-N-SH NVHCPG9tTnWwY4Tpc44hSXO|YYm= MlrXOU8yOCEQvF2= M4rHPVQ5KGh? MkjMSG1UVw>? NFe4OZVqdmirYnn0d{BpfW2jbjDORkBk\WyuIH3p[5JifGmxbh?= NVPQRm1WOjR|OUmwO|Q>
SH-SY5Y NX62OGZGTnWwY4Tpc44hSXO|YYm= MVi1M|ExKM7:TR?= MXm0PEBp MorsSG1UVw>? MorsbY5pcWKrdIOgbJVu[W5iTlKgZ4VtdCCvaXfyZZRqd25? MoezNlQ{QTlyN{S=
SK-N-SH NEnNWW5HfW6ldHnvckBCe3OjeR?= NWflNHZUPS9zMDFOwG0> NXHLXo92PDhiaB?= MnLxSG1UVw>? M4rOeYlvcGmkaYTzJIh2dWGwIF7CJINmdGxiaX72ZZNqd25? M3\wO|I1Ozl7MEe0
SH-SY5Y MlqxSpVv[3Srb36gRZN{[Xl? M3TydlUwOTBizszN NF3nfY01QCCq MlzySG1UVw>? MUHpcohq[mm2czDoeY1idiCQQjDj[YxtKGmwdnHzbY9v NHrFd|czPDN7OUC3OC=>
SK-N-SH NFvyXoRHfW6ldHnvckBCe3OjeR?= NV;xXm1JPSEQvF2= Mm\WNlQwPDhxN{KgbC=> NYfiN5N5TE2VTx?= M2nQWJN2eHC{ZYPz[ZMhfGinIHX4dJJme3Orb36gc4YhS1iFUkSgZY5lKE2PUEG0JI1TVkF? M4[4dFI1Ozl7MEe0
SH-SY5Y NEPJZ5FHfW6ldHnvckBCe3OjeR?= MV[1JO69VQ>? NU\RSHFsOjRxNEivO|IhcA>? NHzqdJlFVVOR M2nPfJN2eHC{ZYPz[ZMhfGinIHX4dJJme3Orb36gc4YhS1iFUkSgZY5lKE2PUEG0JI1TVkF? MVeyOFM6QTB5NB?=
SK-N-SH NFLHT4lHfW6ldHnvckBCe3OjeR?= MWK1JO69VQ>? M4LQXVQ5Nzd{IHi= MkjJSG1UVw>? M374O5N2eHC{ZYPz[ZMh\XiycnXzd4lwdiCxZjD0bIUhS1iFUkSgZY5lKE2PUEG0JJBzd3SnaX6= NGG1U5IzPDN7OUC3OC=>
SH-SY5Y NVP2[WZ7TnWwY4Tpc44hSXO|YYm= NWjMR3N7PSEQvF2= M{j1b|Q5Nzd{IHi= NUi5b3ZWTE2VTx?= NE\QUJh{fXCycnXzd4V{KGW6cILld5Nqd25ib3[geIhmKEO[Q2K0JIFv\CCPTWCxOEBxem:2ZXnu NVLzWWFkOjR|OUmwO|Q>
HMEpC MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUX0cpVoOSCwTT2xNFAh|ryP MkXQOFjDqGkEoB?= MX3EUXNQ NEDLc5lqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NEXafmozPDF|OEi0Ny=>
MCF-7 NFXrfIpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGeybYIyKG6PLUGwNEDPxE1? NU\TeY5{PDkEoHlCpC=> MXvEUXNQ MW\pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MU[yOFE{QDh2Mx?=
ZR-75-1 NEfzUIVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEK2WlIyKG6PLUGwNEDPxE1? MoD6OFjDqGkEoB?= NYXON4ZGTE2VTx?= NX;3[HpFcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M2LZ[lI1OTN6OESz
MDA-MB-231 M{nD[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIWwbIoyKG6PLUGwNEDPxE1? MWW0POKhcMLi Mkf1SG1UVw>? MXnpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NXfUTJdkOjRzM{i4OFM>
MDA-MB-468 MlL4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4Gxb|Ehdk1vMUCwJO69VQ>? NV\NW|N7PDkEoHlCpC=> M3[4V2ROW09? Ml[xbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MWeyOFE{QDh2Mx?=
T-47-D NFXuXIFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWmxJI5ONTFyMDFOwG0> NXP5N3VnPDkEoHlCpC=> M4fTZ2ROW09? MlHZbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NV7wSFJuOjRzM{i4OFM>
U251  M2\1PWZ2dmO2aX;uJGF{e2G7 NYLSTGlMOi92L{lihKnPxOLGs9Mg M3vr[FYwOTJxMkSgbC=> NGXGcI9FVVOR MX;pcoNz\WG|ZYOgeIhmKEyFMz3JTUBt\X[nbDDpckBiKHSrbXWt[IVx\W6mZX70JIFv\CCmb4PlMYRmeGWwZHXueEBu[W6wZYK= NWjrT4VxOjN5OUm4OVI>
U87MG MWHGeY5kfGmxbjDBd5NigQ>? M4G2WlIwPC964pEJ{tzjjLQEoB?= M4[0clYwOTJxMkSgbC=> Ml7wSG1UVw>? Mn70bY5kemWjc3XzJJRp\SCOQ{OtTWkhdGW4ZXygbY4h[SC2aX3lMYRmeGWwZHXueEBidmRiZH;z[U1l\XCnbnTlcpQhdWGwbnXy MmjqNlM4QTl6NUK=
U251  MWPGeY5kfGmxbjDBd5NigQ>? MmGzOQKBkc7:4pUzxsA> NHHYOpQzNzZxMUKgbC=> NF:xU2lFVVOR MnLrd5VxeHKnc4Pld{Bj[XOjbDDs[ZZmdHNib3[gdIhwe3Cqb4L5cIF1cW:wIH;mJHM3KCiVMkO1M|I{PiluIETFMWJROSBqVEO3M|Q3MSxiYX7kJGFsfCBqU{S3N{khcW5iYTD0bY1mNWSncHXu[IVvfCCvYX7u[ZLDqA>? MkTFNlM4QTl6NUK=
U87MG NWLFeZlJTnWwY4Tpc44hSXO|YYm= M3L1SVTjiIoQvPMEt:Kh MkmyNk83NzF{IHi= M2\X[GROW09? MlfBd5VxeHKnc4Pld{Bj[XOjbDDs[ZZmdHNib3[gdIhwe3Cqb4L5cIF1cW:wIH;mJHM3KCiVMkO1M|I{PiluIETFMWJROSBqVEO3M|Q3MSxiYX7kJGFsfCBqU{S3N{khcW5iYTD0bY1mNWSncHXu[IVvfCCvYX7u[ZLDqA>? NH\KZXMzOzd7OUi1Ni=>
H1650  NVPtNYNOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmTPTWM2OD1|LkZCtVEvOiEQvF2= NXLsbINTOjN{N{S3OVg>
HUVECs  MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX:3NkBp NGfPfFZKSzVywrC9JFcvOSEQvH3vcE9N NIjqeWwzOjZzMUCyOy=>
KYN-2  M2DwU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2LHfVczKGh? NEfBSodKSzVywrC9JFgvOSEQvH3vcE9N MXGyNlYyOTB{Nx?=
HuH-7  Ml;RS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmHSO|IhcA>? M2TPZ2lEPTEEoE2gPU41KM7:bX;sM2w> MoTINlI3OTFyMke=
HUVECs  NWf2TnRRTnWwY4Tpc44hSXO|YYm= M2rvclEwPS9zMDFOwG0> M{faflEhcA>? M1XZTpNq\26rZnnjZY51dHliaX7obYJqfHNiVlXHSnIuOiCyaH;zdIhwenmuYYTpc44> M1\5PVIzPjFzMEK3
HAK1-B NVzwUFdxTnWwY4Tpc44hSXO|YYm= NEHGS3QyNzVxMUCg{txO M2K1OVEhcA>? NH3WSnh{fXCycnXzd4V{KEWJRmKgdIhwe3Cqb4L5cIF1cW:w MU[yNlYyOTB{Nx?=
UM-22A MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXe4VIo{OC14IN88US=> MonzO|IhcA>? MVjEUXNQ MVvpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M1HUW|IzOzB5N{O1
UM-22B M4jOWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYWwMVYh|ryP MVO3NkBp M4LSemROW09? MnWxbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M1PSOFIzOzB5N{O1
PCI-37A NFHITmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYKwMVYh|ryP MYK3NkBp M1zWW2ROW09? M1zpPIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz Ml;INlI{ODd5M{W=
PCI-37B NVG2XpZbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX[wMVYh|ryP Ml\HO|IhcA>? M{Dve2ROW09? M3\VbIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M3e5RVIzOzB5N{O1
PCI-15B NGHVV|lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXP3RnRqOC14IN88US=> NHXKRWg4OiCq MUfEUXNQ M1GwfIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MX2yNlMxPzd|NR?=
SCC-25 NELpb|JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{\odFAuPiEQvF2= NH\XRWM4OiCq MorFSG1UVw>? MXXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MVyyNlMxPzd|NR?=
UM-22A NXGxdVBTTnWwY4Tpc44hSXO|YYm= NYfzcWFjOC1zMDFOwG0> MlfmNlQhcA>? M2r4[mROW09? M1\0N4lvcGmkaYTzJJRp\SCjY4TpeoF1cW:wIH;mJJRp\SCHR1\SJJR6em:|aX7lJItqdmG|ZTDhcoQh[Wy|bzDk[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ib3[gdIhwe3Cqb4L5cIF1\WRiZn;ycZMhd2ZidHjlJIRwf26|dILlZY0he2mpbnHsbY5oKGWuZX3lcpR{NCCVVFHUN{BidmRiTVHQTy=> NXTleoRNOjJ|MEe3N|U>
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PCI-15B MX7GeY5kfGmxbjDBd5NigQ>? M3LHUVAuOTBizszN MkTUNlQhcA>? NYDhe4F5TE2VTx?= MYnpcohq[mm2czD0bIUh[WO2aY\heIlwdiCxZjD0bIUhTUeIUjD0fZJwe2mwZTDrbY5ie2ViYX7kJIFte29iZHXjdoVie2W|IITo[UBmgHC{ZYPzbY9vKG:oIIDoc5NxcG:{eXzheIVlKG[xcn3zJI9nKHSqZTDkc5dve3S{ZXHtJJNq\26jbHnu[{BmdGWvZX70d{whW1SDVEOgZY5lKE2DUFu= NW\2RpZ1OjJ|MEe3N|U>
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201T  NUPYOWVDTnWwY4Tpc44hSXO|YYm= NIi0OGUyNzVxMUCg{txO NWnRdXc1PDhiaB?= MmKySG1UVw>? MkHUZoxw[2u|IITo[UBxcG:|cHjvdplt[XSrb36gc4YhSWu2IHnu[JVk\WRiYomgWmVITkN? NVjM[21pOjJ{NUi0O|Y>
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RT4 NIfCRm1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXP6VHlJOC1{MDFOwG0> NIrUSIwzPMLiaB?= NH7jOnlqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MnvUNVkzOjB{NU[=
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CRL1749 M4XVSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2[4RlAuOjBizszN NHHEOFAzPMLiaB?= MV;pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MX6xPVIzODJ3Nh?=
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ACC3 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUf6SVJnOC1zMDFOwG0> NX7IT4wzPzJiaB?= M1nFNYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz Ml\ONVg3QThyMkW=
ACC2 NVHp[457T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Moq4NE0yOCEQvF2= M{PidVczKGh? M1;udIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MVexPFY6QDB{NR?=
ACCM MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnXMNE0yOCEQvF2= MXq3NkBp M4DQ[4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M1\adlE5Pjl6MEK1
ACC3 MlThRZBweHSxc3nzbUBCe3OjeR?= NELMXmMxNTFyIN88US=> M4TqXFczKGh? MlfvbY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= NXLlVZF2OTh4OUiwNlU>
ACC2 MVjBdI9xfG:|aYPpJGF{e2G7 MWKwMVExKM7:TR?= M1rmTVczKGh? NIfiV2tqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 NG\XZm0yQDZ7OECyOS=>
ACCM MW\BdI9xfG:|aYPpJGF{e2G7 M3\QW|AuOTBizszN MlfqO|IhcA>? Mk\SbY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= MnewNVg3QThyMkW=
EHMES-1 MkPkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlfQO|IhcA>? NX;6c|hbTE2VTx?= Ml3PTWM2OD1zMD62JO69VQ>? NU\3WI1iOTh|NkSyOFg>
EHMES-10 M4TSRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NESzPIQ4OiCq Mo\oSG1UVw>? NH\PZ5FKSzVyPUCuN{DPxE1? MUOxPFM3PDJ2OB?=
211H MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWPZcXMxPzJiaB?= NH61eFdFVVOR NWfQbJJTUUN3ME2yMlIh|ryP M4jkcFE5OzZ2MkS4
H28 MkT1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkTQO|IhcA>? MoWxSG1UVw>? MVzJR|UxRTFwODFOwG0> M2nLPFE5OzZ2MkS4
H2052 Ml3NS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFvxcoQ4OiCq NFq5SXJFVVOR NFXtTGRKSzVyPUiuNEDPxE1? MYKxPFM3PDJ2OB?=
H2452 NX7OTod{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3rseFczKGh? NVSxcpp[TE2VTx?= M3u0UmlEPTB;NT61JO69VQ>? NVzvbJdEOTh|NkSyOFg>
CNE-1 Mnv5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF32S3gxNjFvMkWuOkDPxE1? MYC0PEBp NXrkUWp2UUN3ME2zMlYh|ryP NHHUO2oyPzZ|MU[0Oi=>
CNE-2 M1Owb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NU\iOYk{OC5zLUK1MlYh|ryP NVvpN3MxPDhiaB?= NV61V5c5UUN3ME22MlIh|ryP MluxNVc3OzF4NE[=
C666-1 NIC1TJhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWSwMlEuOjVwNjFOwG0> NW\iZlA{PDhiaB?= M1HIVGlEPTB;MkOuOEDPxE1? MoftNVc3OzF4NE[=
CNE-1 M{foN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUmwMlEuOjVwNjFOwG0> M2nobFczKGh? NU\uSlhvUUN3ME2yMlMh|ryP MXexO|Y{OTZ2Nh?=
CNE-2 NWTBXIR5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHLRW2gxNjFvMkWuOkDPxE1? NFrl[4Y4OiCq NW[wfWJTUUN3ME2zMlYh|ryP NVGzboVjOTd4M{G2OFY>
C666-1 NHexPYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4fOblAvOS1{NT62JO69VQ>? MorNO|IhcA>? NUTjc3dzUUN3ME20Mlg3KM7:TR?= MWOxO|Y{OTZ2Nh?=
CNE-1 M3q2O2Z2dmO2aX;uJGF{e2G7 NHXG[ng3KM7:TR?= MWiyOEBp MUDk[YxigXNiR{CvS|Eh[2WubDDjfYNt\SCycn;ndoV{e2mxbh?= M{nlXFE4PjNzNkS2
CNE-2 M4eyWmZ2dmO2aX;uJGF{e2G7 Mk\pOkDPxE1? M4XpUlI1KGh? NGD0[opl\WyjeYOgS|AwTzFiY3XscEBkgWOuZTDwdo9oemW|c3nvci=> M3LjVlE4PjNzNkS2
C666-1 MojqSpVv[3Srb36gRZN{[Xl? NUXxbnk6PiEQvF2= MknBNlQhcA>? NWD2cGY4\GWuYYnzJGcxN0dzIHPlcIwh[3mlbHWgdJJw\3Knc4Ppc44> M{W0flE4PjNzNkS2

... 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 Insoluble
Ethanol 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
Synonyms N/A

Bio Calculators

Molarity Calculator

Molarity Calculator

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

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*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

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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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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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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