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  MXnGeY5kfGmxbjDBd5NigQ>? M1;XcVUxOOLCiX7NxsA> MlqxNVYhcA>? MXTpcoNz\WG|ZYOgR3hEWjRiZYjwdoV{e2mxbjDzbYdvcW[rY3HueIx6 NH3sOWszPTZ5Nk[5NS=>
SN186 NXru[|lVTnWwY4Tpc44hSXO|YYm= NV2xfG14PTBy4pEJcm3DqA>? NES1T|cyPiCq Mn7zbY5kemWjc3XzJGNZS1J2IHX4dJJme3Orb36gd4lodmmoaXPhcpRtgQ>? MUeyOVY4PjZ7MR?=
SN179  M2TqVWZ2dmO2aX;uJGF{e2G7 MX[1NFDjiImwTdMg NGPkdI4yPiCq MV\lcohidmOnczD0bIUhS1iFTEGyJIRqemWldHXkJI1q\3KjdHnvci=> NGrtd4kzPTZ5Nk[5NS=>
SN179  M2DVTWZ2dmO2aX;uJGF{e2G7 MlKzOVAx6oDLbl5CpC=> M1LuO|E3KGh? NH;GXotqdmO{ZXHz[ZMh[mG|YXygcYloemG2aX;uxsA> NUS5TYpFOjV4N{[2PVE>
Jurkat M1f0TWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3jmb|czyqCqwrC= MmjOS2k2OD1zLkWgxtEhOC5{IN88US=> NWTNZo1uOjR4OEGyNFU>
K-562 NYrPNnlrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3v6NVczyqCqwrC= M{LBU2dKPTB;MT64JOKyKDBwMTFOwG0> MkPkNlQ3QDF{MEW=
NCTC-2544 NH7zWFRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX;DOXk6PzMEoHlCpC=> MoLtS2k2OD12Lk[gxtEhOC5|IN88US=> NG\hZWUzPDZ6MUKwOS=>
A-431 NVn1[442T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYr5[|BKPzMEoHlCpC=> NYHH[pRjT0l3ME2yMlQhyrFiMD6zJO69VQ>? M2jCelI1PjhzMkC1
SK-N-SH NV\4cGZ2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mmf5NE43OjVvMkCg{txO NFXVZm01QCCq NVH5W25oTE2VTx?= NIHkXGJqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M1u0bFI1Ozl7MEe0
SH-SY5Y NIq5XGZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3PLZlAvPjJ3LUKwJO69VQ>? NGLoR|k1QCCq MYfEUXNQ MkLsbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MmjjNlQ{QTlyN{S=
SK-N-SH MUfBdI9xfG:|aYPpJGF{e2G7 NW\GbWdsPS9zMD:yNEDPxE1? NHXhd4w1QCCq M3XGNmROW09? MkTLbY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= M2jSfVI1Ozl7MEe0
SH-SY5Y M4W4UmFxd3C2b4Ppd4khSXO|YYm= MXK1M|ExNzJyIN88US=> MlLXOFghcA>? M2TOUWROW09? Mo\DbY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= Mk\0NlQ{QTlyN{S=
SK-N-SH NXzOSJNJTnWwY4Tpc44hSXO|YYm= MkTYOU8yOC9{MDFOwG0> M16xVlQ5KGh? NVvSSlIzTE2VTx?= MoTybY5lfWOnczDHNUBxcGG|ZTDj[YxtKGO7Y3zlJIFzemW|dB?= MonTNlQ{QTlyN{S=
SH-SY5Y NEj0[pBHfW6ldHnvckBCe3OjeR?= NVfVSG9QPS9zMD:yNEDPxE1? MUm0PEBp NIDCSWpFVVOR NWn4fFR1cW6mdXPld{BIOSCyaHHz[UBk\WyuIHP5Z4xmKGG{cnXzeC=> NIDndZUzPDN7OUC3OC=>
SK-N-SH NILxbHhHfW6ldHnvckBCe3OjeR?= Mnm1NU82NzFyIN88US=> NFTrZlE1QCCq NWLN[2ZjTE2VTx?= MkXXbY5pcWKrdIOgVmVVKHCqb4PwbI9zgWyjdHnvci=> M1PLdlI1Ozl7MEe0
SH-SY5Y NVPiU|RoTnWwY4Tpc44hSXO|YYm= MYmxM|UwOTBizszN M4ToW|Q5KGh? Mn\vSG1UVw>? NF61UFZqdmirYnn0d{BTTVRicHjvd5Bpd3K7bHH0bY9v M{LtelI1Ozl7MEe0
SK-N-SH MYfGeY5kfGmxbjDBd5NigQ>? NILFOpI2NzFyIN88US=> MYi0PEBp MYDEUXNQ Ml3tbY5pcWKrdIOgbJVu[W5iTlKgZ4VtdCCvaXfyZZRqd25? NFzJc4QzPDN7OUC3OC=>
SH-SY5Y Mmr0SpVv[3Srb36gRZN{[Xl? NFPjOWU2NzFyIN88US=> NEHVWYU1QCCq NFH0SHRFVVOR Mmm0bY5pcWKrdIOgbJVu[W5iTlKgZ4VtdCCvaXfyZZRqd25? NEnsW4YzPDN7OUC3OC=>
SK-N-SH NEfvRlFHfW6ldHnvckBCe3OjeR?= MojIOU8yOCEQvF2= NIrMO3M1QCCq NUHCW4I3TE2VTx?= NV6xT3lDcW6qaXLpeJMhcHWvYX6gUmIh[2WubDDpcpZie2mxbh?= NHXDNY4zPDN7OUC3OC=>
SH-SY5Y NXja[HBtTnWwY4Tpc44hSXO|YYm= M4nGN|UwOTBizszN NH\DTXY1QCCq MWnEUXNQ NUH5Xo9PcW6qaXLpeJMhcHWvYX6gUmIh[2WubDDpcpZie2mxbh?= M2f1UFI1Ozl7MEe0
SK-N-SH Ml;USpVv[3Srb36gRZN{[Xl? NFTEOnk2KM7:TR?= Mm\INlQwPDhxN{KgbC=> MXfEUXNQ M{\ycpN2eHC{ZYPz[ZMhfGinIHX4dJJme3Orb36gc4YhS1iFUkSgZY5lKE2PUEG0JI1TVkF? NHfLSoQzPDN7OUC3OC=>
SH-SY5Y MYPGeY5kfGmxbjDBd5NigQ>? MlzhOUDPxE1? NUHUPXd{OjRxNEivO|IhcA>? NGf1NXlFVVOR M{fZO5N2eHC{ZYPz[ZMhfGinIHX4dJJme3Orb36gc4YhS1iFUkSgZY5lKE2PUEG0JI1TVkF? NF;Oe28zPDN7OUC3OC=>
SK-N-SH NH3IUHZHfW6ldHnvckBCe3OjeR?= Mn64OUDPxE1? NEfVW|Q1QC95MjDo NUSwR5lQTE2VTx?= MkHBd5VxeHKnc4Pld{BmgHC{ZYPzbY9vKG:oIITo[UBEYEOUNDDhcoQhVU2SMUSgdJJwfGWrbh?= NIT2bmwzPDN7OUC3OC=>
SH-SY5Y MXnGeY5kfGmxbjDBd5NigQ>? M{\MNFUh|ryP NGjjZ5Y1QC95MjDo MXXEUXNQ NX\w[pdse3WycILld5NmeyCneIDy[ZN{cW:wIH;mJJRp\SCFWFPSOEBidmRiTV3QNVQheHKxdHXpci=> MVSyOFM6QTB5NB?=
HMEpC MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmXPNUBvVS1zMECg{txO MlTpOFjDqGkEoB?= MXnEUXNQ NYP2ZpVPcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M{TvcVI1OTN6OESz
MCF-7 M2Ll[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1zpXlEhdk1vMUCwJO69VQ>? NI\FdYo1QMLiaNMg NUfZc49HTE2VTx?= M{HPSYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NFTqXJMzPDF|OEi0Ny=>
ZR-75-1 NXXXSVdYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnTWNUBvVS1zMECg{txO M{DVelQ5yqCqwrC= M3Pr[GROW09? NYG5OHA4cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MYGyOFE{QDh2Mx?=
MDA-MB-231 NF3FfWNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH3Sb48yKG6PLUGwNEDPxE1? M4HsTFQ5yqCqwrC= MkDiSG1UVw>? Ml7kbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M2m0V|I1OTN6OESz
MDA-MB-468 M1zVOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWWxJI5ONTFyMDFOwG0> NYnBOIJjPDkEoHlCpC=> M1HycWROW09? MYHpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> Mnu3NlQyOzh6NEO=
T-47-D NHLpPIpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Moe1NUBvVS1zMECg{txO M2G0WFQ5yqCqwrC= MUHEUXNQ Mm\lbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NFrOcFEzPDF|OEi0Ny=>
U251  M2jTV2Z2dmO2aX;uJGF{e2G7 M2ToclIwPC964pEJ{tzjjLQEoB?= NInKcYY3NzF{L{K0JIg> MmXxSG1UVw>? MknzbY5kemWjc3XzJJRp\SCOQ{OtTWkhdGW4ZXygbY4h[SC2aX3lMYRmeGWwZHXueEBidmRiZH;z[U1l\XCnbnTlcpQhdWGwbnXy MVyyN|c6QTh3Mh?=
U87MG M1[xO2Z2dmO2aX;uJGF{e2G7 M3;BflIwPC964pEJ{tzjjLQEoB?= NF3FdWQ3NzF{L{K0JIg> NV;zSmF{TE2VTx?= MWjpcoNz\WG|ZYOgeIhmKEyFMz3JTUBt\X[nbDDpckBiKHSrbXWt[IVx\W6mZX70JIFv\CCmb4PlMYRmeGWwZHXueEBu[W6wZYK= NEf0OVczOzd7OUi1Ni=>
U251  NWi5[lRDTnWwY4Tpc44hSXO|YYm= NG\pepk16oDLzs|iiNPDqA>? M1e3S|IwPi9zMjDo M1Pr[mROW09? M1iyN5N2eHC{ZYPz[ZMh[mG|YXygcIV3\Wy|IH;mJJBpd3OyaH;yfYxifGmxbjDv[kBUPiBqU{KzOU8zOzZrLDC0SU1DWDFiKGSzO{81PiluIHHu[EBCc3RiKGO0O|MqKGmwIHGgeIlu\S2mZYDlcoRmdnRibXHucoVzyqB? NWDHdY5nOjN5OUm4OVI>
U87MG NI[3clNHfW6ldHnvckBCe3OjeR?= NYTKZoJ{POLCid885qS{yqB? M2fwXFIwPi9zMjDo MlPpSG1UVw>? MV\zeZBxemW|c3XzJIJie2GuIHzleoVteyCxZjDwbI9{eGixconsZZRqd25ib3[gV|YhMFN{M{WvNlM3MSxiNFWtRnAyKCiWM{evOFYqNCCjbnSgRYt1KCiVNEezLUBqdiCjIITpcYUu\GWyZX7k[Y51KG2jbn7lduKh NXT6ZYZJOjN5OUm4OVI>
H1650  NY\XZm9sT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml3ZTWM2OD1|LkZCtVEvOiEQvF2= Mn22NlMzPzR5NUi=
HUVECs  NXnUOJdoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUPNeZJVPzJiaB?= Mk\5TWM2OMLiPTC3MlEh|ryvb3yvUC=> MkHMNlI3OTFyMke=
KYN-2  NHvUTXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXSyVYNIPzJiaB?= NXHHU2VYUUN3MNMgQUA5NjFizsztc4wwVA>? MWGyNlYyOTB{Nx?=
HuH-7  NHfr[pJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUS3NkBp MnHiTWM2OMLiPTC5MlQh|ryvb3yvUC=> MWSyNlYyOTB{Nx?=
HUVECs  MWrGeY5kfGmxbjDBd5NigQ>? NX;Mc4ZNOS93L{GwJO69VQ>? MVmxJIg> NHu3UJl{cWewaX\pZ4FvfGy7IHnubIljcXS|IG\FS2ZTNTJicHjvd5Bpd3K7bHH0bY9v NILMPXozOjZzMUCyOy=>
HAK1-B NUXXcHB1TnWwY4Tpc44hSXO|YYm= NX;Q[VZpOS93L{GwJO69VQ>? M2HFfVEhcA>? M{P5cZN2eHC{ZYPz[ZMhTUeIUjDwbI9{eGixconsZZRqd25? Mm\ONlI3OTFyMke=
UM-22A MmP3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVi2Nm5xOC14IN88US=> NXuxTnFyPzJiaB?= NGPvO21FVVOR NVnidYF6cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? Mo\nNlI{ODd5M{W=
UM-22B MmjFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWPJVnh6OC14IN88US=> M2TIdVczKGh? NEmwb4RFVVOR NYWwUoV3cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NH65RmwzOjNyN{ezOS=>
PCI-37A MnixS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYjmfmFzOC14IN88US=> MV23NkBp NEPlb3JFVVOR MVXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NXLVepZ2OjJ|MEe3N|U>
PCI-37B MoiwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYqwMVYh|ryP MYG3NkBp NG\DU5JFVVOR MXXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M123VFIzOzB5N{O1
PCI-15B NW\JPYdpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH3FSYsxNTZizszN M3The|czKGh? MmLoSG1UVw>? M2PkcYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NHu2bI4zOjNyN{ezOS=>
SCC-25 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY[5[ZRLOC14IN88US=> Mmj6O|IhcA>? M1HzWGROW09? MVfpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NYPRTGxCOjJ|MEe3N|U>
UM-22A MoK3SpVv[3Srb36gRZN{[Xl? MXmwMVExKM7:TR?= NFLWOHQzPCCq MmTMSG1UVw>? NUfaVmpucW6qaXLpeJMhfGinIHHjeIl3[XSrb36gc4YhfGinIFXHSnIhfHm{b4PpcoUhc2mwYYPlJIFv\CCjbIPvJIRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDv[kBxcG:|cHjvdplt[XSnZDDmc5JueyCxZjD0bIUh\G:5boP0doVidSC|aXfuZYxqdmdiZXzlcYVvfHNuIGPURXQ{KGGwZDDNRXBM Ml;2NlI{ODd5M{W=
UM-22B NHmxcVBHfW6ldHnvckBCe3OjeR?= M{ex[|AuOTBizszN MlfONlQhcA>? MmXWSG1UVw>? M{HQPIlvcGmkaYTzJJRp\SCjY4TpeoF1cW:wIH;mJJRp\SCHR1\SJJR6em:|aX7lJItqdmG|ZTDhcoQh[Wy|bzDk[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ib3[gdIhwe3Cqb4L5cIF1\WRiZn;ycZMhd2ZidHjlJIRwf26|dILlZY0he2mpbnHsbY5oKGWuZX3lcpR{NCCVVFHUN{BidmRiTVHQTy=> NVnkdmNjOjJ|MEe3N|U>
PCI-15B NYL4bFJmTnWwY4Tpc44hSXO|YYm= M1TFNlAuOTBizszN NFT1XGczPCCq MX;EUXNQ MnzHbY5pcWKrdIOgeIhmKGGldHn2ZZRqd25ib3[geIhmKEWJRmKgeJlzd3OrbnWgb4lv[XOnIHHu[EBidHOxIHTlZ5Jm[XOnczD0bIUh\XiycnXzd4lwdiCxZjDwbI9{eGixconsZZRm\CCob4Ltd{Bw\iC2aHWg[I94dnO2cnXhcUB{cWewYXzpcoch\WynbXXueJMtKFOWQWSzJIFv\CCPQWDL NEHtZ48zOjNyN{ezOS=>
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RT4 M360d2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3r2XlAuOjBizszN MXiyOOKhcA>? M4L6dolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MV6xPVIzODJ3Nh?=
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CRL1749 M3;XUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{fLTVAuOjBizszN NVjuOoE{OjUEoHi= NVjZVm4{cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M{jlW|E6OjJyMkW2
T24 NWPUSXlTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX:wMVIxKM7:TR?= M1K5c|I1yqCq M{PkNYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M4DrcVE6OjJyMkW2
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ACC3 NVvCOJNjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEnZ[24xNTFyIN88US=> MojxO|IhcA>? MmXJbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MWexPFY6QDB{NR?=
ACC2 M2PsfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHfvNIcxNTFyIN88US=> NEn2R3Q4OiCq M1;WZ4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NYfMOZFHOTh4OUiwNlU>
ACCM NHTme2FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1;kb|AuOTBizszN NXzONI9lPzJiaB?= MVPpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MYqxPFY6QDB{NR?=
ACC3 NWPaXFhSSXCxcITvd4l{cSCDc4PhfS=> NWjDXI5IOC1zMDFOwG0> M1vmV|czKGh? MW\pcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 M13RN|E5Pjl6MEK1
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EHMES-10 MontS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlfFO|IhcA>? M2X0OmROW09? NYfm[JJlUUN3ME2wMlMh|ryP NUmxUVF6OTh|NkSyOFg>
211H M1jOVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlzQO|IhcA>? MlPjSG1UVw>? M2O2VGlEPTB;Mj6yJO69VQ>? NGLuUlIyQDN4NEK0PC=>
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CNE-1 M4Hx[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHzwXWcxNjFvMkWuOkDPxE1? NXHab2FWPDhiaB?= NUS1ZY9kUUN3ME2zMlYh|ryP Mnq5NVc3OzF4NE[=
CNE-2 NVG1Z5FZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV:wMlEuOjVwNjFOwG0> NIqzV2E1QCCq M1\nb2lEPTB;Nj6yJO69VQ>? MX2xO|Y{OTZ2Nh?=
C666-1 NUDCW3ZuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX\COGNOOC5zLUK1MlYh|ryP NGfCbFY1QCCq NWP6ZYZIUUN3ME2yN{41KM7:TR?= NYKwRWZWOTd4M{G2OFY>
CNE-1 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mlm1NE4yNTJ3Lk[g{txO M3q0ZlczKGh? M1HxXWlEPTB;Mj6zJO69VQ>? NH71bmwyPzZ|MU[0Oi=>
CNE-2 NGLZe4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXzmNmtqOC5zLUK1MlYh|ryP M3HoW|czKGh? NXzDd3ZkUUN3ME2zMlYh|ryP MWCxO|Y{OTZ2Nh?=
C666-1 NFXKe2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGrUZY8xNjFvMkWuOkDPxE1? NIHwcYQ4OiCq MXLJR|UxRTRwOE[g{txO NIH3[WkyPzZ|MU[0Oi=>
CNE-1 NUnENZpUTnWwY4Tpc44hSXO|YYm= MkP3OkDPxE1? M{\NWlI1KGh? NEPnOG9l\WyjeYOgS|AwTzFiY3XscEBkgWOuZTDwdo9oemW|c3nvci=> NFu1eJUyPzZ|MU[0Oi=>
CNE-2 NELxNWZHfW6ldHnvckBCe3OjeR?= NGrGTGw3KM7:TR?= NVrHSJFJOjRiaB?= M3zmOYRmdGG7czDHNE9IOSClZXzsJIN6[2ynIIDyc4dz\XO|aX;u NY\uRZR7OTd4M{G2OFY>
C666-1 MnzlSpVv[3Srb36gRZN{[Xl? NYPDR4lMPiEQvF2= NEmw[HMzPCCq NVvFVVhH\GWuYYnzJGcxN0dzIHPlcIwh[3mlbHWgdJJw\3Knc4Ppc44> MUixO|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 Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
1% CMC Na
For best results, use promptly after mixing.
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

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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