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  MWnGeY5kfGmxbjDBd5NigQ>? Ml\FOVAx6oDLbl5CpC=> M4DHbVE3KGh? MW\pcoNz\WG|ZYOgR3hEWjRiZYjwdoV{e2mxbjDzbYdvcW[rY3HueIx6 NV7CSJJnOjV4N{[2PVE>
SN186 NX35eFdsTnWwY4Tpc44hSXO|YYm= NVG2ZpJ[PTBy4pEJcm3DqA>? NXu1NZhNOTZiaB?= Mln3bY5kemWjc3XzJGNZS1J2IHX4dJJme3Orb36gd4lodmmoaXPhcpRtgQ>? NHvMNGMzPTZ5Nk[5NS=>
SN179  M1\OZWZ2dmO2aX;uJGF{e2G7 M1LjVVUxOOLCiX7NxsA> NUf3SY43OTZiaB?= MX3lcohidmOnczD0bIUhS1iFTEGyJIRqemWldHXkJI1q\3KjdHnvci=> M2HjWlI2Pjd4Nkmx
SN179  NGXUW5ZHfW6ldHnvckBCe3OjeR?= M33S[|UxOOLCiX7NxsA> NHzVW2MyPiCq NWfpT2lrcW6lcnXhd4V{KGKjc3HsJI1q\3KjdHnvcuKh NFvxdpIzPTZ5Nk[5NS=>
Jurkat MlTJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoC0O|LDqGkEoB?= M4jydWdKPTB;MT61JOKyKDBwMjFOwG0> MUiyOFY5OTJyNR?=
K-562 NWfBU5VlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHPUfHA4OsLiaNMg MXzHTVUxRTFwODFCtUAxNjFizszN NXW2UYRGOjR4OEGyNFU>
NCTC-2544 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MW[3NuKhcMLi NUj1cJJsT0l3ME20MlYhyrFiMD6zJO69VQ>? MVeyOFY5OTJyNR?=
A-431 NVXJW5J2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3rMN|czyqCqwrC= MXfHTVUxRTJwNDFCtUAxNjNizszN MUKyOFY5OTJyNR?=
SK-N-SH Mnz4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1Xpd|AvPjJ3LUKwJO69VQ>? MUG0PEBp NXXvRYVMTE2VTx?= NHzRfHFqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NVzv[XljOjR|OUmwO|Q>
SH-SY5Y MnPzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2faS|AvPjJ3LUKwJO69VQ>? MUC0PEBp NVWxW2R{TE2VTx?= NHr5U|NqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NF;ydGUzPDN7OUC3OC=>
SK-N-SH NX;ETlB4SXCxcITvd4l{cSCDc4PhfS=> NV;YdW9JPS9zMD:yNEDPxE1? MmfqOFghcA>? NYnsdIt1TE2VTx?= MWHpcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 NGfmNVgzPDN7OUC3OC=>
SH-SY5Y NVHPbXNWSXCxcITvd4l{cSCDc4PhfS=> MmP6OU8yOC9{MDFOwG0> NWHEeY1IPDhiaB?= NGC1bY5FVVOR NXOxT4xJcW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> Mlu5NlQ{QTlyN{S=
SK-N-SH M3TkUGZ2dmO2aX;uJGF{e2G7 NYe1NXNmPS9zMD:yNEDPxE1? NEX6NVg1QCCq MYrEUXNQ MYLpcoR2[2W|IFexJJBp[XOnIHPlcIwh[3mlbHWgZZJz\XO2 NUf4eI1pOjR|OUmwO|Q>
SH-SY5Y MV\GeY5kfGmxbjDBd5NigQ>? MmHxOU8yOC9{MDFOwG0> M3fB[|Q5KGh? M{XQOGROW09? NIXWNoJqdmS3Y3XzJGcyKHCqYYPlJINmdGxiY4njcIUh[XK{ZYP0 Mlm5NlQ{QTlyN{S=
SK-N-SH NXTmVIxRTnWwY4Tpc44hSXO|YYm= MmSyNU82NzFyIN88US=> MlTiOFghcA>? M{HtZmROW09? MWHpcohq[mm2czDSSXQheGixc4Doc5J6dGG2aX;u M3L0fVI1Ozl7MEe0
SH-SY5Y NXzDc3plTnWwY4Tpc44hSXO|YYm= NH7LTVEyNzVxMUCg{txO M{m4Z|Q5KGh? NVzoXo9nTE2VTx?= MoS0bY5pcWKrdIOgVmVVKHCqb4PwbI9zgWyjdHnvci=> MW[yOFM6QTB5NB?=
SK-N-SH M4jmWmZ2dmO2aX;uJGF{e2G7 MojrOU8yOCEQvF2= NFLRXHI1QCCq M4TKXWROW09? NYrLOJl1cW6qaXLpeJMhcHWvYX6gUmIh[2WubDDtbYdz[XSrb36= MljJNlQ{QTlyN{S=
SH-SY5Y NHLqW4tHfW6ldHnvckBCe3OjeR?= NUPLd5BXPS9zMDFOwG0> NIflWXc1QCCq M4DIfmROW09? NWT6RXBTcW6qaXLpeJMhcHWvYX6gUmIh[2WubDDtbYdz[XSrb36= MX6yOFM6QTB5NB?=
SK-N-SH NWnVOIdrTnWwY4Tpc44hSXO|YYm= MU[1M|ExKM7:TR?= MUK0PEBp NFToT5JFVVOR MXjpcohq[mm2czDoeY1idiCQQjDj[YxtKGmwdnHzbY9v NUDNdZhCOjR|OUmwO|Q>
SH-SY5Y NH\JTY5HfW6ldHnvckBCe3OjeR?= NHHKNpY2NzFyIN88US=> MlnvOFghcA>? M17RNGROW09? MUPpcohq[mm2czDoeY1idiCQQjDj[YxtKGmwdnHzbY9v MkHjNlQ{QTlyN{S=
SK-N-SH M2C2d2Z2dmO2aX;uJGF{e2G7 MnHJOUDPxE1? NVHWTINiOjRxNEivO|IhcA>? M3PHTWROW09? Mkf4d5VxeHKnc4Pld{B1cGViZYjwdoV{e2mxbjDv[kBEYEOUNDDhcoQhVU2SMUSgcXJPSQ>? NGeydnQzPDN7OUC3OC=>
SH-SY5Y MVnGeY5kfGmxbjDBd5NigQ>? MX[1JO69VQ>? NFvVeXAzPC92OD:3NkBp M1j2V2ROW09? MVrzeZBxemW|c3XzJJRp\SCneIDy[ZN{cW:wIH;mJGNZS1J2IHHu[EBOVVBzNDDtVm5C M1Tab|I1Ozl7MEe0
SK-N-SH NUPwZVdqTnWwY4Tpc44hSXO|YYm= M1G5OlUh|ryP MX[0PE84OiCq MYnEUXNQ NUfmSIVPe3WycILld5NmeyCneIDy[ZN{cW:wIH;mJJRp\SCFWFPSOEBidmRiTV3QNVQheHKxdHXpci=> NFLvblczPDN7OUC3OC=>
SH-SY5Y M3vQRmZ2dmO2aX;uJGF{e2G7 MV21JO69VQ>? M321SlQ5Nzd{IHi= NGT3VVVFVVOR MkXMd5VxeHKnc4Pld{BmgHC{ZYPzbY9vKG:oIITo[UBEYEOUNDDhcoQhVU2SMUSgdJJwfGWrbh?= NWjCcpF[OjR|OUmwO|Q>
HMEpC M3vNdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYD3T|c2OSCwTT2xNFAh|ryP NV;k[GtwPDkEoHlCpC=> MVfEUXNQ MULpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M{LtclI1OTN6OESz
MCF-7 NGnhUZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M173T|Ehdk1vMUCwJO69VQ>? NEH6ZYw1QMLiaNMg NIj5eIRFVVOR MnXTbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NFntcYozPDF|OEi0Ny=>
ZR-75-1 M1LxbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWKxTFJDOSCwTT2xNFAh|ryP Mmm5OFjDqGkEoB?= NVLWO2JQTE2VTx?= M4rafYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NEjrU4EzPDF|OEi0Ny=>
MDA-MB-231 NF3kVpVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUnY[pQ6OSCwTT2xNFAh|ryP MoO1OFjDqGkEoB?= M1\ybWROW09? NWroV|BVcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NILwVG8zPDF|OEi0Ny=>
MDA-MB-468 M1vQS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEfj[G4yKG6PLUGwNEDPxE1? M4q0cVQ5yqCqwrC= M{jnUGROW09? NXTOVFFxcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? Mn\rNlQyOzh6NEO=
T-47-D NU\PeJNwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXz5XZhJOSCwTT2xNFAh|ryP MlnCOFjDqGkEoB?= NYixSYhjTE2VTx?= MX\pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NWL0TlZCOjRzM{i4OFM>
U251  MnuySpVv[3Srb36gRZN{[Xl? NVi2ZXJmOi92L{lihKnPxOLGs9Mg NUjKcpJbPi9zMj:yOEBp MXjEUXNQ NVf3OotbcW6lcnXhd4V{KHSqZTDMR|MuUUlibHX2[YwhcW5iYTD0bY1mNWSncHXu[IVvfCCjbnSg[I9{\S2mZYDlcoRmdnRibXHucoVz MWiyN|c6QTh3Mh?=
U87MG M{\wcGZ2dmO2aX;uJGF{e2G7 NVjOb5RpOi92L{lihKnPxOLGs9Mg NVu2ZZdWPi9zMj:yOEBp M1ywTWROW09? MnLVbY5kemWjc3XzJJRp\SCOQ{OtTWkhdGW4ZXygbY4h[SC2aX3lMYRmeGWwZHXueEBidmRiZH;z[U1l\XCnbnTlcpQhdWGwbnXy M12yWFI{Pzl7OEWy
U251  NHXLWpVHfW6ldHnvckBCe3OjeR?= Ml;ROQKBkc7:4pUzxsA> MlnXNk83NzF{IHi= M13ueGROW09? NI\sbnJ{fXCycnXzd4V{KGKjc3HsJIxmfmWuczDv[kBxcG:|cHjvdplt[XSrb36gc4YhWzZiKGOyN|UwOjN4KTygOGUuSlBzIDjUN|cwPDZrLDDhcoQhSWu2IDjTOFc{MSCrbjDhJJRqdWVvZHXw[Y5l\W62IH3hco5mesLi NXjvZVFJOjN5OUm4OVI>
U87MG MlTZSpVv[3Srb36gRZN{[Xl? MmHvOQKBkc7:4pUzxsA> NVLP[pM3Oi94L{GyJIg> M4fEOGROW09? MX7zeZBxemW|c3XzJIJie2GuIHzleoVteyCxZjDwbI9{eGixconsZZRqd25ib3[gV|YhMFN{M{WvNlM3MSxiNFWtRnAyKCiWM{evOFYqNCCjbnSgRYt1KCiVNEezLUBqdiCjIITpcYUu\GWyZX7k[Y51KG2jbn7lduKh NW\6TYpHOjN5OUm4OVI>
H1650  M17CTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIPGfIFKSzVyPUOuOeKyOS5{IN88US=> MmrsNlMzPzR5NUi=
HUVECs  M{mwUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV23cHpkPzJiaB?= NEDLb3hKSzVywrC9JFcvOSEQvH3vcE9N NWG4WmVqOjJ4MUGwNlc>
KYN-2  NFrTTItIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MW[3NkBp MULJR|UxyqB;IEiuNUDPxG2xbD;M MlXRNlI3OTFyMke=
HuH-7  MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVi3NkBp M4GzdGlEPTEEoE2gPU41KM7:bX;sM2w> MnzJNlI3OTFyMke=
HUVECs  NHf2Z3NHfW6ldHnvckBCe3OjeR?= MVuxM|UwOTBizszN MXKxJIg> MV3zbYdvcW[rY3HueIx6KGmwaHnibZR{KF[HR1\SMVIheGixc4Doc5J6dGG2aX;u M{jQRlIzPjFzMEK3
HAK1-B MVrGeY5kfGmxbjDBd5NigQ>? M1;BVlEwPS9zMDFOwG0> NFr5[FgyKGh? MXnzeZBxemW|c3XzJGVITlJicHjvd5Bpd3K7bHH0bY9v MmXkNlI3OTFyMke=
UM-22A Mne2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4TaXFAuPiEQvF2= NWPGSYg1PzJiaB?= MkD2SG1UVw>? M3TFcolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NFy5XXgzOjNyN{ezOS=>
UM-22B M3;kOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NG\QOo8xNTZizszN NVS5b|ZlPzJiaB?= MV\EUXNQ M{\GWYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MoftNlI{ODd5M{W=
PCI-37A NVK4[mp{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnfGNE03KM7:TR?= M3fpe|czKGh? M{HZ[WROW09? NEi1eoNqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M2fuXlIzOzB5N{O1
PCI-37B NHLWSYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvWNE03KM7:TR?= Mly1O|IhcA>? MkjISG1UVw>? NIrSZWNqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NW[3d2QxOjJ|MEe3N|U>
PCI-15B MknGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1nE[VAuPiEQvF2= NXztcHl7PzJiaB?= NYG4e4FmTE2VTx?= NVX0TXB1cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M1:3d|IzOzB5N{O1
SCC-25 M3foemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NU[2OFI5OC14IN88US=> NEfG[o84OiCq NW\2dpB3TE2VTx?= M{nN[YlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NGTqVnozOjNyN{ezOS=>
UM-22A MY\GeY5kfGmxbjDBd5NigQ>? NWrqNlVbOC1zMDFOwG0> M4j5PVI1KGh? MnzISG1UVw>? NUPyc|hOcW6qaXLpeJMhfGinIHHjeIl3[XSrb36gc4YhfGinIFXHSnIhfHm{b4PpcoUhc2mwYYPlJIFv\CCjbIPvJIRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDv[kBxcG:|cHjvdplt[XSnZDDmc5JueyCxZjD0bIUh\G:5boP0doVidSC|aXfuZYxqdmdiZXzlcYVvfHNuIGPURXQ{KGGwZDDNRXBM M4W4U|IzOzB5N{O1
UM-22B NH:ySoNHfW6ldHnvckBCe3OjeR?= MXGwMVExKM7:TR?= NE\4d4gzPCCq NY\vTnVsTE2VTx?= NFH4SnpqdmirYnn0d{B1cGViYXP0bZZifGmxbjDv[kB1cGViRVfGVkB1gXKxc3nu[UBscW6jc3WgZY5lKGGuc3:g[IVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIH;mJJBpd3OyaH;yfYxifGWmIH\vdo1{KG:oIITo[UBld3ewc4Ty[YFuKHOrZ37hcIlv\yCnbHXt[Y51eyxiU2TBWFMh[W6mIF3BVGs> MlfwNlI{ODd5M{W=
PCI-15B NGCwN4ZHfW6ldHnvckBCe3OjeR?= M{HLZ|AuOTBizszN MmfpNlQhcA>? NX\Hd2RxTE2VTx?= MmTCbY5pcWKrdIOgeIhmKGGldHn2ZZRqd25ib3[geIhmKEWJRmKgeJlzd3OrbnWgb4lv[XOnIHHu[EBidHOxIHTlZ5Jm[XOnczD0bIUh\XiycnXzd4lwdiCxZjDwbI9{eGixconsZZRm\CCob4Ltd{Bw\iC2aHWg[I94dnO2cnXhcUB{cWewYXzpcoch\WynbXXueJMtKFOWQWSzJIFv\CCPQWDL MVmyNlMxPzd|NR?=
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201T  NXTBenRTTnWwY4Tpc44hSXO|YYm= MmryNU82NzFyIN88US=> MWK0PEBp MVrEUXNQ MojoZoxw[2u|IITo[UBxcG:|cHjvdplt[XSrb36gc4YhSWu2IHnu[JVk\WRiYomgWmVITkN? NWr5W3d7OjJ{NUi0O|Y>
H2052 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnK0TWM2OD1zLkC3xtExNjB2IN88US=> M4TpU|IyQTdyOEe0
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HT1376 M{HBWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFLBeVExNTJyIN88US=> M4G3[lI1yqCq NV3SdIExcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? Ml[3NVkzOjB{NU[=
RT4 MlHDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVr6RXh4OC1{MDFOwG0> Ml7LNlTDqGh? NYDZPVFzcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? Mme1NVkzOjB{NU[=
J82 NXe2RWxuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIL5VowxNTJyIN88US=> NY\seVFvOjUEoHi= MV;pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MXGxPVIzODJ3Nh?=
CRL1749 NV7yNYd7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWfpT29yOC1{MDFOwG0> MVOyOOKhcA>? M2\KSolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NYfHO4dJOTl{MkCyOVY>
T24 NVn6e|FVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWOwMVIxKM7:TR?= MnTmNlTDqGh? NF;CWYZqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M37MNFE6OjJyMkW2
SUP MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWqwMVIxKM7:TR?= M{fMO|I1yqCq NELGeWpqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MYmxPVIzODJ3Nh?=
HTB9 NWj4dIozT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn3qNE0zOCEQvF2= MY[yOOKhcA>? NISwT41qdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? Mlz6NVkzOjB{NU[=
ACC3 NWfpOWZuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWTRfHhFOC1zMDFOwG0> MWS3NkBp MmnRbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NG\iT5IyQDZ7OECyOS=>
ACC2 NEHMWmtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1y3bVAuOTBizszN MmLHO|IhcA>? NFz1b4lqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NW\mPJY4OTh4OUiwNlU>
ACCM MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoroNE0yOCEQvF2= NX;GT3RMPzJiaB?= NYfjT5c{cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MmnxNVg3QThyMkW=
ACC3 MUjBdI9xfG:|aYPpJGF{e2G7 NHzh[YIxNTFyIN88US=> MkniO|IhcA>? NFz0Vm1qdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 NWfCXYt[OTh4OUiwNlU>
ACC2 MkDYRZBweHSxc3nzbUBCe3OjeR?= Moq0NE0yOCEQvF2= MoDQO|IhcA>? MYLpcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 MYqxPFY6QDB{NR?=
ACCM NY\FU5hDSXCxcITvd4l{cSCDc4PhfS=> MljyNE0yOCEQvF2= NUfrRVdZPzJiaB?= M1nCe4lv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= MWSxPFY6QDB{NR?=
EHMES-1 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnWzO|IhcA>? NIPTcWlFVVOR MnG3TWM2OD1zMD62JO69VQ>? M3\DVlE5OzZ2MkS4
EHMES-10 NHfoXnhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkW1O|IhcA>? MlHCSG1UVw>? M1jrVmlEPTB;MD6zJO69VQ>? NWjvSo1oOTh|NkSyOFg>
211H M4jvXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYKwfGFRPzJiaB?= NFT3UXNFVVOR MXjJR|UxRTJwMjFOwG0> NYDuNlVPOTh|NkSyOFg>
H28 M3i5R2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1q4dVczKGh? NY\RTZpPTE2VTx?= MmfpTWM2OD1zLkig{txO NXPPd|VmOTh|NkSyOFg>
H2052 M3H2Tmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmnVO|IhcA>? NV\1V|c2TE2VTx?= NHWyUWxKSzVyPUiuNEDPxE1? NGLyOVkyQDN4NEK0PC=>
H2452 MoXCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWG3NkBp NHK2XFlFVVOR Mm\hTWM2OD13LkWg{txO NFLYV4kyQDN4NEK0PC=>
CNE-1 NI\vbnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1XkZVAvOS1{NT62JO69VQ>? MWK0PEBp M16wdGlEPTB;Mz62JO69VQ>? M4nqOVE4PjNzNkS2
CNE-2 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4\pdlAvOS1{NT62JO69VQ>? M1XjZlQ5KGh? MXHJR|UxRTZwMjFOwG0> NIjUUncyPzZ|MU[0Oi=>
C666-1 Ml7wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXewMlEuOjVwNjFOwG0> MXi0PEBp M1LwUWlEPTB;MkOuOEDPxE1? MYexO|Y{OTZ2Nh?=
CNE-1 NGqyTopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{\ld|AvOS1{NT62JO69VQ>? M2nYb|czKGh? NG\GcW9KSzVyPUKuN{DPxE1? M4XibVE4PjNzNkS2
CNE-2 M3LVNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIrGVnMxNjFvMkWuOkDPxE1? NFLkOok4OiCq NF3DS49KSzVyPUOuOkDPxE1? Mn6xNVc3OzF4NE[=
C666-1 M2XPSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M17QTFAvOS1{NT62JO69VQ>? M2H0dlczKGh? NYXQ[4FoUUN3ME20Mlg3KM7:TR?= MXSxO|Y{OTZ2Nh?=
CNE-1 NIHPRYtHfW6ldHnvckBCe3OjeR?= MXO2JO69VQ>? Ml\3NlQhcA>? Mori[IVt[Xm|IFewM2cyKGOnbHygZ5lkdGVicILv[5Jme3Orb36= NIHLTnoyPzZ|MU[0Oi=>
CNE-2 MVPGeY5kfGmxbjDBd5NigQ>? M2TDc|Yh|ryP M1P3blI1KGh? NWi0cZVC\GWuYYnzJGcxN0dzIHPlcIwh[3mlbHWgdJJw\3Knc4Ppc44> MUGxO|Y{OTZ2Nh?=
C666-1 MUTGeY5kfGmxbjDBd5NigQ>? MUG2JO69VQ>? NE\NfZMzPCCq NUjyfpFk\GWuYYnzJGcxN0dzIHPlcIwh[3mlbHWgdJJw\3Knc4Ppc44> M1HGbVE4PjNzNkS2

... 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:
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
Synonyms N/A

Bio Calculators

Molarity Calculator

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

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00514046 Active, not recruiting Medullary Thyroid Carcinoma|Multiple Endocrine Neoplasia Type 2A|Multiple Endocrine Neoplasia Type 2B National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) July 9, 2007 Phase 1|Phase 2
NCT02495103 Recruiting Renal Cell Carcinoma|Hereditary Leiomyomatosis and Renal Cell Cancer|Papillary Renal Cell Carcinoma, Sporadic National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) June 30, 2015 Phase 1|Phase 2
NCT00272350 Completed Recurrent High-Grade Gliomas|Progressive Low-Grade Gliomas|Malignant Gliomas National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) December 29, 2005 Phase 1
NCT02638428 Recruiting Relapsed Pediatric Solid Tumor|Refractory Pediatric Solid Tumor|Relapsed Pediatric AML|Refractory Pediatric AML Samsung Medical Center|Ministry of health & welfare, Republic of Korea December 2015 Phase 2
NCT02530411 Recruiting Neoplasms Velindre NHS Trust|Cancer Research UK|AstraZeneca April 2015 Phase 2
NCT02239952 Recruiting Cancer|High-grade Glioma VU University Medical Center November 2014 --

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID