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  Ml7LSpVv[3Srb36gRZN{[Xl? MVS1NFDjiImwTdMg M3;3NFE3KGh? MlzwbY5kemWjc3XzJGNZS1J2IHX4dJJme3Orb36gd4lodmmoaXPhcpRtgQ>? Ml3xNlU3PzZ4OUG=
SN186 MnXtSpVv[3Srb36gRZN{[Xl? MYm1NFDjiImwTdMg Ml6zNVYhcA>? MnSybY5kemWjc3XzJGNZS1J2IHX4dJJme3Orb36gd4lodmmoaXPhcpRtgQ>? NV\Rdnp{OjV4N{[2PVE>
SN179  NHftWoNHfW6ldHnvckBCe3OjeR?= M4PDU|UxOOLCiX7NxsA> MYqxOkBp M3:1XYVvcGGwY3XzJJRp\SCFWFPMNVIh\Gm{ZXP0[YQhdWmpcnH0bY9v MUGyOVY4PjZ7MR?=
SN179  NFrLfXJHfW6ldHnvckBCe3OjeR?= MYO1NFDjiImwTdMg MXOxOkBp MofCbY5kemWjc3XzJIJie2GuIH3p[5JifGmxbtMg MlTqNlU3PzZ4OUG=
Jurkat MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUPObpNMPzMEoHlCpC=> NIXHXotIUTVyPUGuOUDDuSByLkKg{txO NX3uVJJkOjR4OEGyNFU>
K-562 Mk\GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYP1[nM1PzMEoHlCpC=> NY[xdpZTT0l3ME2xMlghyrFiMD6xJO69VQ>? MlvvNlQ3QDF{MEW=
NCTC-2544 NFLqem5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH[1R5I4OsLiaNMg MVPHTVUxRTRwNjFCtUAxNjNizszN M{ntV|I1PjhzMkC1
A-431 NUDJe45IT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7tNI04OsLiaNMg M4n2XWdKPTB;Mj60JOKyKDBwMzFOwG0> MWiyOFY5OTJyNR?=
SK-N-SH MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkXXNE43OjVvMkCg{txO MYO0PEBp NETLRXdFVVOR NHrjcXpqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MWCyOFM6QTB5NB?=
SH-SY5Y M1PoS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmPTNE43OjVvMkCg{txO MUW0PEBp NHy4[VNFVVOR MVnpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NVjzO4NuOjR|OUmwO|Q>
SK-N-SH NVXSdpRLSXCxcITvd4l{cSCDc4PhfS=> NFPZZok2NzFyL{KwJO69VQ>? MVK0PEBp M4rXdGROW09? MmnBbY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= NFPEcHIzPDN7OUC3OC=>
SH-SY5Y NFrrNGhCeG:ydH;zbZNqKEG|c3H5 NIPqWIE2NzFyL{KwJO69VQ>? MYK0PEBp Mmn4SG1UVw>? MmHsbY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= NXzO[WpuOjR|OUmwO|Q>
SK-N-SH M4fMcGZ2dmO2aX;uJGF{e2G7 M3\DXFUwOTBxMkCg{txO MV20PEBp MoXzSG1UVw>? NYHOZ|JlcW6mdXPld{BIOSCyaHHz[UBk\WyuIHP5Z4xmKGG{cnXzeC=> M3jXd|I1Ozl7MEe0
SH-SY5Y M4S0WWZ2dmO2aX;uJGF{e2G7 Mnz1OU8yOC9{MDFOwG0> MX[0PEBp NI\4[IxFVVOR MmHkbY5lfWOnczDHNUBxcGG|ZTDj[YxtKGO7Y3zlJIFzemW|dB?= NVXxSJMxOjR|OUmwO|Q>
SK-N-SH NWmye4FqTnWwY4Tpc44hSXO|YYm= NHi2VGgyNzVxMUCg{txO M1exR|Q5KGh? NX;zbVdKTE2VTx?= NXzpdpJrcW6qaXLpeJMhWkWWIIDoc5NxcG:{eXzheIlwdg>? NFfUOFUzPDN7OUC3OC=>
SH-SY5Y MWPGeY5kfGmxbjDBd5NigQ>? MWCxM|UwOTBizszN MWW0PEBp MoSxSG1UVw>? MoH1bY5pcWKrdIOgVmVVKHCqb4PwbI9zgWyjdHnvci=> MoDsNlQ{QTlyN{S=
SK-N-SH NEXISVlHfW6ldHnvckBCe3OjeR?= NFTpV5U2NzFyIN88US=> MUO0PEBp NHTTbZFFVVOR NVLjcHFXcW6qaXLpeJMhcHWvYX6gUmIh[2WubDDtbYdz[XSrb36= MmDQNlQ{QTlyN{S=
SH-SY5Y NF3mXZhHfW6ldHnvckBCe3OjeR?= NWe1bVBVPS9zMDFOwG0> NVy1cGM3PDhiaB?= MkHMSG1UVw>? M3rTUYlvcGmkaYTzJIh2dWGwIF7CJINmdGxibXnndoF1cW:w M{fFS|I1Ozl7MEe0
SK-N-SH Mkj6SpVv[3Srb36gRZN{[Xl? NEDXUpM2NzFyIN88US=> NGnKZZo1QCCq NULyR3IzTE2VTx?= NUX5O4JxcW6qaXLpeJMhcHWvYX6gUmIh[2WubDDpcpZie2mxbh?= MYmyOFM6QTB5NB?=
SH-SY5Y NVq2RW04TnWwY4Tpc44hSXO|YYm= M2eyVFUwOTBizszN MkPCOFghcA>? NHKwe29FVVOR M1;ldYlvcGmkaYTzJIh2dWGwIF7CJINmdGxiaX72ZZNqd25? MV[yOFM6QTB5NB?=
SK-N-SH MoXuSpVv[3Srb36gRZN{[Xl? M{HzZ|Uh|ryP NUnmbldwOjRxNEivO|IhcA>? NXfGNlNyTE2VTx?= Mn\Yd5VxeHKnc4Pld{B1cGViZYjwdoV{e2mxbjDv[kBEYEOUNDDhcoQhVU2SMUSgcXJPSQ>? Ml7pNlQ{QTlyN{S=
SH-SY5Y M37IbWZ2dmO2aX;uJGF{e2G7 MkXaOUDPxE1? MUOyOE81QC95MjDo MXTEUXNQ Mmfxd5VxeHKnc4Pld{B1cGViZYjwdoV{e2mxbjDv[kBEYEOUNDDhcoQhVU2SMUSgcXJPSQ>? NIXsSXEzPDN7OUC3OC=>
SK-N-SH MYDGeY5kfGmxbjDBd5NigQ>? NVfJU|FpPSEQvF2= M4mxWFQ5Nzd{IHi= MmXYSG1UVw>? M2\R[JN2eHC{ZYPz[ZMh\XiycnXzd4lwdiCxZjD0bIUhS1iFUkSgZY5lKE2PUEG0JJBzd3SnaX6= NVf6SGh3OjR|OUmwO|Q>
SH-SY5Y MY\GeY5kfGmxbjDBd5NigQ>? NFHGNJg2KM7:TR?= MWS0PE84OiCq NG\HS25FVVOR NVXQXphCe3WycILld5NmeyCneIDy[ZN{cW:wIH;mJJRp\SCFWFPSOEBidmRiTV3QNVQheHKxdHXpci=> NEjNUlgzPDN7OUC3OC=>
HMEpC MoP0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlXxNUBvVS1zMECg{txO MV60POKhcMLi M1ewOGROW09? M4K4SYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MmrTNlQyOzh6NEO=
MCF-7 NIrwXGtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHvV[YoyKG6PLUGwNEDPxE1? MUm0POKhcMLi MYLEUXNQ MWrpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MWGyOFE{QDh2Mx?=
ZR-75-1 M2PHXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoT3NUBvVS1zMECg{txO NXj2ToVCPDkEoHlCpC=> MmPmSG1UVw>? NYjOPZVHcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? Mo[1NlQyOzh6NEO=
MDA-MB-231 M3PyNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGLNdmwyKG6PLUGwNEDPxE1? NFTqVpQ1QMLiaNMg NWm3d5duTE2VTx?= NYPkS3pycW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M3\wO|I1OTN6OESz
MDA-MB-468 NIX3eldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIK2e24yKG6PLUGwNEDPxE1? MYS0POKhcMLi MVTEUXNQ MW\pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NFfu[|UzPDF|OEi0Ny=>
T-47-D NVO5cFZoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX7kO|Z4OSCwTT2xNFAh|ryP NVzuenQ2PDkEoHlCpC=> NISye4RFVVOR M2Dk[IlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M3vLRVI1OTN6OESz
U251  MWnGeY5kfGmxbjDBd5NigQ>? NUDvfJBiOi92L{lihKnPxOLGs9Mg M3vGPVYwOTJxMkSgbC=> M3T4[GROW09? NHqzdoJqdmO{ZXHz[ZMhfGinIFzDN{1KUSCuZY\lcEBqdiCjIITpcYUu\GWyZX7k[Y51KGGwZDDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> NYTvfGZZOjN5OUm4OVI>
U87MG NXXxcXdUTnWwY4Tpc44hSXO|YYm= M3jmSFIwPC964pEJ{tzjjLQEoB?= MYO2M|EzNzJ2IHi= NYnwV|V1TE2VTx?= MlG0bY5kemWjc3XzJJRp\SCOQ{OtTWkhdGW4ZXygbY4h[SC2aX3lMYRmeGWwZHXueEBidmRiZH;z[U1l\XCnbnTlcpQhdWGwbnXy NFHjXGUzOzd7OUi1Ni=>
U251  MlrCSpVv[3Srb36gRZN{[Xl? MXq05qCK|r{khMRCpC=> MWCyM|YwOTJiaB?= NX75PIh7TE2VTx?= NEKybnh{fXCycnXzd4V{KGKjc3HsJIxmfmWuczDv[kBxcG:|cHjvdplt[XSrb36gc4YhWzZiKGOyN|UwOjN4KTygOGUuSlBzIDjUN|cwPDZrLDDhcoQhSWu2IDjTOFc{MSCrbjDhJJRqdWVvZHXw[Y5l\W62IH3hco5mesLi M17xcVI{Pzl7OEWy
U87MG M2nBdGZ2dmO2aX;uJGF{e2G7 MXi05qCK|r{khMRCpC=> Mlr1Nk83NzF{IHi= NFzFfWZFVVOR NWXqXlJ6e3WycILld5NmeyCkYYPhcEBt\X[nbIOgc4YheGixc4Doc5J6dGG2aX;uJI9nKFN4IDjTNlM2NzJ|NjmsJFRGNUKSMTCoWFM4NzR4KTygZY5lKEGtdDCoV|Q4OyliaX6gZUB1cW2nLXTldIVv\GWwdDDtZY5v\XMEoB?= MkjWNlM4QTl6NUK=
H1650  NXXnbWgyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmH3TWM2OD1|LkZCtVEvOiEQvF2= NXPGVm81OjN{N{S3OVg>
HUVECs  NUTUc3VQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWf2U5IyPzJiaB?= Mln3TWM2OMLiPTC3MlEh|ryvb3yvUC=> NWHH[oJ{OjJ4MUGwNlc>
KYN-2  NGLxWmRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEKzU284OiCq MkW1TWM2OMLiPTC4MlEh|ryvb3yvUC=> MYCyNlYyOTB{Nx?=
HuH-7  MoP0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIPT[284OiCq MUfJR|UxyqB;IEmuOEDPxG2xbD;M M1Xv[|IzPjFzMEK3
HUVECs  M1TuRWZ2dmO2aX;uJGF{e2G7 MoTWNU82NzFyIN88US=> NWrLb2h{OSCq MYTzbYdvcW[rY3HueIx6KGmwaHnibZR{KF[HR1\SMVIheGixc4Doc5J6dGG2aX;u MXeyNlYyOTB{Nx?=
HAK1-B M37hWmZ2dmO2aX;uJGF{e2G7 MormNU82NzFyIN88US=> NWLFXnZuOSCq Ml;hd5VxeHKnc4Pld{BGT0[UIIDoc5NxcG:{eXzheIlwdg>? M33K[FIzPjFzMEK3
UM-22A NHriPWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnrlNE03KM7:TR?= MkXXO|IhcA>? NH;JeFBFVVOR NUS0ZYRicW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NWrHSpI3OjJ|MEe3N|U>
UM-22B MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoLKNE03KM7:TR?= MYG3NkBp NXy2PVF1TE2VTx?= M4D5PYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NVjDNIZmOjJ|MEe3N|U>
PCI-37A Mn;zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEDQTYMxNTZizszN NY\4[Jp6PzJiaB?= NVHVcpVGTE2VTx?= MUXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MkThNlI{ODd5M{W=
PCI-37B M1nycWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWD1[YN2OC14IN88US=> NYfvSFRXPzJiaB?= NIjUPIFFVVOR NVHFdoNrcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NV24e4lGOjJ|MEe3N|U>
PCI-15B M3Tycmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGTC[5UxNTZizszN M33GdFczKGh? M{\3OWROW09? MXrpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NWH0SGhiOjJ|MEe3N|U>
SCC-25 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoTSNE03KM7:TR?= Mn24O|IhcA>? M4nJN2ROW09? MVvpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NYTGSYM1OjJ|MEe3N|U>
UM-22A NV:4NXQ1TnWwY4Tpc44hSXO|YYm= NHXNTWIxNTFyIN88US=> MmK4NlQhcA>? M3;hfWROW09? NG[5NZlqdmirYnn0d{B1cGViYXP0bZZifGmxbjDv[kB1cGViRVfGVkB1gXKxc3nu[UBscW6jc3WgZY5lKGGuc3:g[IVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIH;mJJBpd3OyaH;yfYxifGWmIH\vdo1{KG:oIITo[UBld3ewc4Ty[YFuKHOrZ37hcIlv\yCnbHXt[Y51eyxiU2TBWFMh[W6mIF3BVGs> MVeyNlMxPzd|NR?=
UM-22B M4j1cGZ2dmO2aX;uJGF{e2G7 NXK5U|FoOC1zMDFOwG0> NUS2O21xOjRiaB?= MYfEUXNQ M{ftXolvcGmkaYTzJJRp\SCjY4TpeoF1cW:wIH;mJJRp\SCHR1\SJJR6em:|aX7lJItqdmG|ZTDhcoQh[Wy|bzDk[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ib3[gdIhwe3Cqb4L5cIF1\WRiZn;ycZMhd2ZidHjlJIRwf26|dILlZY0he2mpbnHsbY5oKGWuZX3lcpR{NCCVVFHUN{BidmRiTVHQTy=> NWTrN3c5OjJ|MEe3N|U>
PCI-15B NFj5SolHfW6ldHnvckBCe3OjeR?= Mm\xNE0yOCEQvF2= NUfs[FgxOjRiaB?= MWLEUXNQ M3vUc4lvcGmkaYTzJJRp\SCjY4TpeoF1cW:wIH;mJJRp\SCHR1\SJJR6em:|aX7lJItqdmG|ZTDhcoQh[Wy|bzDk[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ib3[gdIhwe3Cqb4L5cIF1\WRiZn;ycZMhd2ZidHjlJIRwf26|dILlZY0he2mpbnHsbY5oKGWuZX3lcpR{NCCVVFHUN{BidmRiTVHQTy=> MUWyNlMxPzd|NR?=
PCI-37A M4HTO2Z2dmO2aX;uJGF{e2G7 MXSxJO69VQ>? NInqWY4zPCCq M2HiSGROW09? M2nOTIRwf26{ZXf1cIF1\XNiVlXHSkBxem:mdXP0bY9v NUPIeJdIOjJ|MEe3N|U>
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A549 MmfKSpVv[3Srb36gRZN{[Xl? NGOxd|UzNjVizszN NEftOpM1QCCq NXP3NJN2TE2VTx?= MVvpcohq[mm2czDwbI9{eGixLV3BVGsh\m:ubH;3bY5oKEWJRh?= MV[yNlI2QDR5Nh?=
201T  Mm\mSpVv[3Srb36gRZN{[Xl? MkmzNU82NzFyIN88US=> NFvNVmw1QCCq NGXnXGpFVVOR NWnxZ4tR[myxY3vzJJRp\SCyaH;zdIhwenmuYYTpc44hd2ZiQXv0JIlv\HWlZXSgZpkhXkWJRlO= M17SV|IzOjV6NEe2
H2052 M{fQWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoXWTWM2OD1zLkC3xtExNjB2IN88US=> NUjsVFhjOjF7N{C4O|Q>
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MSTO-211H MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGiwTG1KSzVyPUGuOFLDuTBwMEOg{txO NULSXopxOjF7N{C4O|Q>
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C643 M1TOSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1Xo[FczKGh? MknFSG1UVw>? NEjKVJJKSzVyPUOuOlUhyrFiMT6yNkDPxE1? NIP5d4kzOTJ{MES3Oy=>
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SW1736 NE\HPHBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGPISGU4OiCq NH;MXmNFVVOR NIqwbYZKSzVyPUmuNFUhyrFiMD61OUDPxE1? NG\0d2ozOTJ{MES3Oy=>
Hth7 MkO2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVvSUZl3PzJiaB?= NXPsdJRwTE2VTx?= M3zTV2lEPTB;OT62OkDDuSByLkO4JO69VQ>? M2fhRVIyOjJyNEe3
Hth104 M17LTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV:3NkBp MXHEUXNQ Ml;hTWM2OD4EsUG2Mlk5KMLzIF7BJO69VQ>? NEjmUGIzOTJ{MES3Oy=>
HTB3 NIH4VWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYfUOY9tOC1{MDFOwG0> NHLk[FUzPMLiaB?= NV3TW4t3cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MkLmNVkzOjB{NU[=
HT1376 NV6yW|RHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1jzTFAuOjBizszN MXeyOOKhcA>? MYjpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NWq4S3RQOTl{MkCyOVY>
RT4 NYrrc3dwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVHNVHZROC1{MDFOwG0> NH7iNZkzPMLiaB?= M2jKb4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MVqxPVIzODJ3Nh?=
J82 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVnrV4NLOC1{MDFOwG0> MVGyOOKhcA>? NImwPXlqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M2LNblE6OjJyMkW2
CRL1749 MnfXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVTxPXg{OC1{MDFOwG0> MkjMNlTDqGh? MkDvbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MX2xPVIzODJ3Nh?=
T24 NWjqVGg5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7aZ2IxNTJyIN88US=> NGXIeHAzPMLiaB?= NX75eWVRcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MXKxPVIzODJ3Nh?=
SUP NGjrV5dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXfFVW1JOC1{MDFOwG0> MkToNlTDqGh? NELC[Y1qdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NWfoXGxFOTl{MkCyOVY>
HTB9 NV3JOY1ET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mki3NE0zOCEQvF2= NF;pNoczPMLiaB?= MoLabY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MkjKNVkzOjB{NU[=
ACC3 NX\SbJFwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkfQNE0yOCEQvF2= MUO3NkBp NVq1cIlTcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MkWxNVg3QThyMkW=
ACC2 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmX1NE0yOCEQvF2= M1zEOFczKGh? M2nmWIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MVGxPFY6QDB{NR?=
ACCM MoPhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkK5NE0yOCEQvF2= MUC3NkBp MoT2bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NE\Meo0yQDZ7OECyOS=>
ACC3 NH\vbJFCeG:ydH;zbZNqKEG|c3H5 NFr5fo0xNTFyIN88US=> NWPxXJNOPzJiaB?= M2[xfYlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= MWKxPFY6QDB{NR?=
ACC2 M36zPWFxd3C2b4Ppd4khSXO|YYm= NXnTOYNqOC1zMDFOwG0> NFXBbZg4OiCq MWLpcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 MUKxPFY6QDB{NR?=
ACCM MVnBdI9xfG:|aYPpJGF{e2G7 MWmwMVExKM7:TR?= NIHqVHQ4OiCq NHjEOHJqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 MnH6NVg3QThyMkW=
EHMES-1 NG\3UZdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHzRZnQ4OiCq NUfYflhiTE2VTx?= M322d2lEPTB;MUCuOkDPxE1? NUntc2JVOTh|NkSyOFg>
EHMES-10 NHrvVYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoXHO|IhcA>? NXK2TJZCTE2VTx?= M2TkZWlEPTB;MD6zJO69VQ>? NWq2WYhJOTh|NkSyOFg>
211H MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIPZVpY4OiCq NEnmcFdFVVOR M4PzSWlEPTB;Mj6yJO69VQ>? Mk\5NVg{PjR{NEi=
H28 Ml6wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnPsO|IhcA>? M{jHbmROW09? M13R[GlEPTB;MT64JO69VQ>? NWf3OY51OTh|NkSyOFg>
H2052 MnHNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4XXdVczKGh? NH3Y[pFFVVOR MoPFTWM2OD16LkCg{txO NX3FPY9qOTh|NkSyOFg>
H2452 NXPZe2VpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUnZcVZtPzJiaB?= NGjxN|FFVVOR MV7JR|UxRTVwNTFOwG0> M13GXVE5OzZ2MkS4
CNE-1 NUXBenVnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWLyeXZYOC5zLUK1MlYh|ryP NWXnR5h6PDhiaB?= NUnMS2E1UUN3ME2zMlYh|ryP NF7hZ4MyPzZ|MU[0Oi=>
CNE-2 NGP0RoRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkH5NE4yNTJ3Lk[g{txO Ml3WOFghcA>? Mo\3TWM2OD14LkKg{txO NYXLeVdrOTd4M{G2OFY>
C666-1 NF3aNFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVuwMlEuOjVwNjFOwG0> NHrEUG81QCCq NUDXXGtyUUN3ME2yN{41KM7:TR?= M{jESlE4PjNzNkS2
CNE-1 M3fyRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUGwMlEuOjVwNjFOwG0> NFHQboQ4OiCq M3nxW2lEPTB;Mj6zJO69VQ>? MUOxO|Y{OTZ2Nh?=
CNE-2 NEHyUJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn\BNE4yNTJ3Lk[g{txO NXvISWhIPzJiaB?= NImyeHBKSzVyPUOuOkDPxE1? M3u3NVE4PjNzNkS2
C666-1 MmjlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXKwMlEuOjVwNjFOwG0> NIfwbmg4OiCq MYnJR|UxRTRwOE[g{txO M3L1RlE4PjNzNkS2
CNE-1 MkfiSpVv[3Srb36gRZN{[Xl? NXGyTXd4PiEQvF2= NXPvWXppOjRiaB?= MWTk[YxigXNiR{CvS|Eh[2WubDDjfYNt\SCycn;ndoV{e2mxbh?= M{\GWFE4PjNzNkS2
CNE-2 NVX0TVRYTnWwY4Tpc44hSXO|YYm= Mnz0OkDPxE1? MkPFNlQhcA>? NI\WdVdl\WyjeYOgS|AwTzFiY3XscEBkgWOuZTDwdo9oemW|c3nvci=> NG\SS24yPzZ|MU[0Oi=>
C666-1 MVvGeY5kfGmxbjDBd5NigQ>? NXXsUpNpPiEQvF2= MXmyOEBp Mn\O[IVt[Xm|IFewM2cyKGOnbHygZ5lkdGVicILv[5Jme3Orb36= M2D2bVE4PjNzNkS2

... 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

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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Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

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Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

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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
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) July 8 2015 Phase 1|Phase 2
NCT00410761 Active not recruiting Thyroid Cancer Genzyme a Sanofi Company|Sanofi November 30 2006 Phase 3
NCT00537095 Active not recruiting Thyroid Neoplasms Genzyme a Sanofi Company|Sanofi September 29 2007 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
NCT01298323 Active not recruiting Locally Advanced or Metastatic Medullary Thyroid Cancer|Medullary Thyroid Cancer Genzyme a Sanofi Company|Sanofi February 25 2011 Phase 3
NCT02530411 Recruiting Neoplasms Velindre NHS Trust|Cancer Research UK|AstraZeneca April 2015 Phase 2

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