Vandetanib (ZD6474)

Catalog No.S1046

For research use only.

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. Vandetanib (ZD6474) increases apoptosis and induces autophagy by increasing the level of reactive oxygen species (ROS).

Vandetanib (ZD6474) Chemical Structure

CAS No. 443913-73-3

Selleck's Vandetanib (ZD6474) has been cited by 97 publications

Purity & Quality Control

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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. Vandetanib (ZD6474) increases apoptosis and induces autophagy by increasing the level of reactive oxygen species (ROS).
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  NWPiUXVuTnWwY4Tpc44hSXO|YYm= MlHZOVAx6oDLbl5CpC=> M3HmUlE3KGh? Mn7mbY5kemWjc3XzJGNZS1J2IHX4dJJme3Orb36gd4lodmmoaXPhcpRtgQ>? NInD[2Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[3OlY6OSd-MkW2O|Y3QTF:L3G+
SN186 MkjRSpVv[3Srb36gRZN{[Xl? MlrFOVAx6oDLbl5CpC=> M{D1RlE3KGh? NHTrWlJqdmO{ZXHz[ZMhS1iFUkSg[ZhxemW|c3nvckB{cWewaX\pZ4FvfGy7 M{TwPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3Nke2OlkyLz5{NU[3OlY6OTxxYU6=
SN179  NV22blVyTnWwY4Tpc44hSXO|YYm= NUHhT3Q6PTBy4pEJcm3DqA>? Mn2yNVYhcA>? NVPzOo1I\W6qYX7j[ZMhfGinIFPYR2wyOiCmaYLlZ5Rm\CCvaXfyZZRqd25? NXHHO|F5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2O|Y3QTFpPkK1Olc3PjlzPD;hQi=>
SN179  NVvqc3BETnWwY4Tpc44hSXO|YYm= M2j2VlUxOOLCiX7NxsA> Mn3LNVYhcA>? NXOzdXRScW6lcnXhd4V{KGKjc3HsJI1q\3KjdHnvcuKh M3zpV|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3Nke2OlkyLz5{NU[3OlY6OTxxYU6=
Jurkat Mk\QS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF\EOZQ4OsLiaNMg NV75O|UyT0l3ME2xMlUhyrFiMD6yJO69VQ>? M2HFTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NkixNlA2Lz5{NE[4NVIxPTxxYU6=
K-562 MmP2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXH4UJZSPzMEoHlCpC=> M3W0PGdKPTB;MT64JOKyKDBwMTFOwG0> NHXNeJM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NE[4NVIxPSd-MkS2PFEzODV:L3G+
NCTC-2544 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{nw[FczyqCqwrC= MmXmS2k2OD12Lk[gxtEhOC5|IN88US=> MoPTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4OEGyNFUoRjJ2NkixNlA2RC:jPh?=
A-431 NY\1e41bT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2XxS|czyqCqwrC= Mki5S2k2OD1{LkSgxtEhOC5|IN88US=> M4Hud|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NkixNlA2Lz5{NE[4NVIxPTxxYU6=
SK-N-SH M3\CZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MojmNE43OjVvMkCg{txO MoHQOFghcA>? MXHEUXNQ MV\pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NWPBeG8zRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzPVkxPzRpPkK0N|k6ODd2PD;hQi=>
SH-SY5Y NF3CZ|VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoLrNE43OjVvMkCg{txO MYG0PEBp NECyO4JFVVOR MmrKbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> Mk\WQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR|OUmwO|QoRjJ2M{m5NFc1RC:jPh?=
SK-N-SH MVXBdI9xfG:|aYPpJGF{e2G7 M2XjT|UwOTBxMkCg{txO MXW0PEBp MWjEUXNQ NWnFR49scW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN7OUC3OEc,OjR|OUmwO|Q9N2F-
SH-SY5Y Mlq5RZBweHSxc3nzbUBCe3OjeR?= M1\Eb|UwOTBxMkCg{txO MUO0PEBp NXPoSHhYTE2VTx?= M4jrb4lv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= NYn6NnpWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzPVkxPzRpPkK0N|k6ODd2PD;hQi=>
SK-N-SH MmHDSpVv[3Srb36gRZN{[Xl? NHHLbGQ2NzFyL{KwJO69VQ>? NV\J[pFiPDhiaB?= NXvLe5ViTE2VTx?= MkfQbY5lfWOnczDHNUBxcGG|ZTDj[YxtKGO7Y3zlJIFzemW|dB?= NICzRnY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO5PVA4PCd-MkSzPVkxPzR:L3G+
SH-SY5Y NFn4RZNHfW6ldHnvckBCe3OjeR?= MonBOU8yOC9{MDFOwG0> MXG0PEBp MnrFSG1UVw>? M3TCbIlv\HWlZYOgS|EheGijc3WgZ4VtdCCleXPs[UBienKnc4S= MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN7OUC3OEc,OjR|OUmwO|Q9N2F-
SK-N-SH MmX4SpVv[3Srb36gRZN{[Xl? MlHvNU82NzFyIN88US=> NVO5UI1vPDhiaB?= MnL4SG1UVw>? NUDSfJppcW6qaXLpeJMhWkWWIIDoc5NxcG:{eXzheIlwdg>? M3[4cVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{m5NFc1Lz5{NEO5PVA4PDxxYU6=
SH-SY5Y Ml\vSpVv[3Srb36gRZN{[Xl? MmXJNU82NzFyIN88US=> Moj1OFghcA>? NXLONZl4TE2VTx?= MnyzbY5pcWKrdIOgVmVVKHCqb4PwbI9zgWyjdHnvci=> NIPKfWg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO5PVA4PCd-MkSzPVkxPzR:L3G+
SK-N-SH MlTKSpVv[3Srb36gRZN{[Xl? NYnqO5llPS9zMDFOwG0> NEPmR2Q1QCCq MX;EUXNQ MlGxbY5pcWKrdIOgbJVu[W5iTlKgZ4VtdCCvaXfyZZRqd25? NEX1OGE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO5PVA4PCd-MkSzPVkxPzR:L3G+
SH-SY5Y NYj6SIgxTnWwY4Tpc44hSXO|YYm= NIL1enc2NzFyIN88US=> NHjEXZg1QCCq NE\pZWNFVVOR NUDHd3RDcW6qaXLpeJMhcHWvYX6gUmIh[2WubDDtbYdz[XSrb36= NIHjVZE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO5PVA4PCd-MkSzPVkxPzR:L3G+
SK-N-SH NIqwcIZHfW6ldHnvckBCe3OjeR?= MnnROU8yOCEQvF2= MX[0PEBp M3vPeGROW09? NULLZmdHcW6qaXLpeJMhcHWvYX6gUmIh[2WubDDpcpZie2mxbh?= M1;4SFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{m5NFc1Lz5{NEO5PVA4PDxxYU6=
SH-SY5Y MlywSpVv[3Srb36gRZN{[Xl? M3vYbVUwOTBizszN NWXiTINNPDhiaB?= NEj5ZoxFVVOR MUnpcohq[mm2czDoeY1idiCQQjDj[YxtKGmwdnHzbY9v NVT3T5JMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzPVkxPzRpPkK0N|k6ODd2PD;hQi=>
SK-N-SH Mn\iSpVv[3Srb36gRZN{[Xl? M4jBOlUh|ryP NW[2fpRROjRxNEivO|IhcA>? MXnEUXNQ MorVd5VxeHKnc4Pld{B1cGViZYjwdoV{e2mxbjDv[kBEYEOUNDDhcoQhVU2SMUSgcXJPSQ>? NVr5bGs{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzPVkxPzRpPkK0N|k6ODd2PD;hQi=>
SH-SY5Y MUnGeY5kfGmxbjDBd5NigQ>? NYD2fWR6PSEQvF2= M1zzSlI1NzR6L{eyJIg> MUPEUXNQ NVvQWFZMe3WycILld5NmeyC2aHWg[ZhxemW|c3nvckBw\iCFWFPSOEBidmRiTV3QNVQhdVKQQR?= NG[zb4c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO5PVA4PCd-MkSzPVkxPzR:L3G+
SK-N-SH MVrGeY5kfGmxbjDBd5NigQ>? NVjmPFFzPSEQvF2= M33N[|Q5Nzd{IHi= NYrSNHFWTE2VTx?= M4rsPZN2eHC{ZYPz[ZMh\XiycnXzd4lwdiCxZjD0bIUhS1iFUkSgZY5lKE2PUEG0JJBzd3SnaX6= NH7qbpE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO5PVA4PCd-MkSzPVkxPzR:L3G+
SH-SY5Y NFSxVppHfW6ldHnvckBCe3OjeR?= NHfPR5k2KM7:TR?= MXm0PE84OiCq MUfEUXNQ MUnzeZBxemW|c3XzJIV5eHKnc4Ppc44hd2ZidHjlJGNZS1J2IHHu[EBOVVBzNDDwdo91\Wmw M2fYSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{m5NFc1Lz5{NEO5PVA4PDxxYU6=
HMEpC MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnvwNUBvVS1zMECg{txO M2HPO|Q5yqCqwrC= MmHRSG1UVw>? M1GzcIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M2XPblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUO4PFQ{Lz5{NEGzPFg1OzxxYU6=
MCF-7 MlHkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFrERnoyKG6PLUGwNEDPxE1? NVLM[pBXPDkEoHlCpC=> NYKwe|c2TE2VTx?= Mn;LbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MkPDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzM{i4OFMoRjJ2MUO4PFQ{RC:jPh?=
ZR-75-1 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYj0NW9XOSCwTT2xNFAh|ryP Ml;NOFjDqGkEoB?= NETPWJFFVVOR MYTpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF|OEi0N{c,OjRzM{i4OFM9N2F-
MDA-MB-231 MofhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXnDT25OOSCwTT2xNFAh|ryP MWS0POKhcMLi MXzEUXNQ NXjhXmt{cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF|OEi0N{c,OjRzM{i4OFM9N2F-
MDA-MB-468 Mk\3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml\SNUBvVS1zMECg{txO MUC0POKhcMLi NIL2cWZFVVOR MUDpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF|OEi0N{c,OjRzM{i4OFM9N2F-
T-47-D M{W0eWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHLnenAyKG6PLUGwNEDPxE1? M4\yRlQ5yqCqwrC= NVq2[IxITE2VTx?= MYLpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF|OEi0N{c,OjRzM{i4OFM9N2F-
U251  Mn;jSpVv[3Srb36gRZN{[Xl? Mme2Nk81NzkkgJpOwQKFu8Li NHnwcGY3NzF{L{K0JIg> MlrISG1UVw>? NFzIdIpqdmO{ZXHz[ZMhfGinIFzDN{1KUSCuZY\lcEBqdiCjIITpcYUu\GWyZX7k[Y51KGGwZDDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> NEWxSZE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5PVg2Oid-MkO3PVk5PTJ:L3G+
U87MG M{HDd2Z2dmO2aX;uJGF{e2G7 M{HsUFIwPC964pEJ{tzjjLQEoB?= NX3EO|RSPi9zMj:yOEBp Mo[1SG1UVw>? MmjubY5kemWjc3XzJJRp\SCOQ{OtTWkhdGW4ZXygbY4h[SC2aX3lMYRmeGWwZHXueEBidmRiZH;z[U1l\XCnbnTlcpQhdWGwbnXy NW\QOYppRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3PVk5PTJpPkKzO|k6QDV{PD;hQi=>
U251  NXjHfJg5TnWwY4Tpc44hSXO|YYm= NV3PV5pJPOLCid885qS{yqB? NXjNRo45Oi94L{GyJIg> M3vRN2ROW09? Mnfud5VxeHKnc4Pld{Bj[XOjbDDs[ZZmdHNib3[gdIhwe3Cqb4L5cIF1cW:wIH;mJHM3KCiVMkO1M|I{PiluIETFMWJROSBqVEO3M|Q3MSxiYX7kJGFsfCBqU{S3N{khcW5iYTD0bY1mNWSncHXu[IVvfCCvYX7u[ZLDqA>? NYPFNXpNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3PVk5PTJpPkKzO|k6QDV{PD;hQi=>
U87MG NHfycmZHfW6ldHnvckBCe3OjeR?= M4OxO|TjiIoQvPMEt:Kh MkT2Nk83NzF{IHi= M{W1[mROW09? M2DTepN2eHC{ZYPz[ZMh[mG|YXygcIV3\Wy|IH;mJJBpd3OyaH;yfYxifGmxbjDv[kBUPiBqU{KzOU8zOzZrLDC0SU1DWDFiKGSzO{81PiluIHHu[EBCc3RiKGO0O|MqKGmwIHGgeIlu\S2mZYDlcoRmdnRibXHucoVzyqB? MlHhQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUm4OVIoRjJ|N{m5PFUzRC:jPh?=
H1650  MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MULJR|UxRTNwNdMxNU4zKM7:TR?= NIrBdXA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{K3OFc2QCd-MkOyO|Q4PTh:L3G+
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KYN-2  NVrUXWJPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYTL[3FzPzJiaB?= M17qcGlEPTEEoE2gPE4yKM7:bX;sM2w> MkXyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ4MUGwNlcoRjJ{NkGxNFI4RC:jPh?=
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Assay
Methods Test Index PMID
Western blot p-EGFR / EGFR ; p-ERK / ERK / p-AKT / AKT 20629091 19622715
Growth inhibition assay Cell viability 24261856
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 (from reference)

Kinase Assay:

[1]

  • 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]

  • 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.

Animal Research:

[5]

  • Animal Models: Female athymic (nu/nu genotype) Swiss mice with PC-3, Calu-6, SKOV-3, and MDA-MB-231 tumors
  • Dosages: 12.5 mg/kg/day, 25 mg/kg/day, 50 mg/kg/day, or 100 mg/kg/day
  • Administration: Oral administration

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

Chemical Information

Molecular Weight 475.35
Formula

C22H24BrFN4O2

CAS No. 443913-73-3
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CN1CCC(CC1)COC2=C(C=C3C(=C2)N=CN=C3NC4=C(C=C(C=C4)Br)F)OC

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03291379 Completed Drug: BTG-002814 Carcinoma Hepatocellular|Metastatic Colorectal Cancer Boston Scientific Corporation|Biocompatibles UK Ltd May 17 2017 Early Phase 1
NCT02495103 Terminated Drug: Vandetanib|Drug: Metformin|Drug: Vandetanib/Metformin Renal Cell Carcinoma|Hereditary Leiomyomatosis|Renal Cell Cancer National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) August 26 2015 Phase 1|Phase 2
NCT02530411 Unknown status Drug: Fulvestrant|Drug: Vandetanib Neoplasms Velindre NHS Trust|Cancer Research UK|AstraZeneca April 2015 Phase 2
NCT02268734 Completed -- Metastatic Sporadic Medullary Thyroid Cancer Fondazione IRCCS Istituto Nazionale dei Tumori Milano April 2014 --
NCT01876784 Active not recruiting Drug: Vandetanib (SAR390530)|Drug: Placebo Differentiated Thyroid Cancer Genzyme a Sanofi Company|Sanofi September 17 2013 Phase 3
NCT01661179 Completed Drug: Vandetanib 300mg Unresectable Locally Advanced or Metastatic Medullary Thyroid Carcinoma Genzyme a Sanofi Company|Sanofi November 2012 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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

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