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  Mnn6SpVv[3Srb36gRZN{[Xl? M1PmS|UxOOLCiX7NxsA> Ml3pNVYhcA>? NXSyd5NMcW6lcnXhd4V{KEO[Q2K0JIV5eHKnc4Ppc44he2mpbnnmbYNidnSueR?= NVH1WY8zOjV4N{[2PVE>
SN186 MmT0SpVv[3Srb36gRZN{[Xl? MXG1NFDjiImwTdMg MkDsNVYhcA>? NWXQ[3lDcW6lcnXhd4V{KEO[Q2K0JIV5eHKnc4Ppc44he2mpbnnmbYNidnSueR?= NUS4R3pMOjV4N{[2PVE>
SN179  NGDvSVVHfW6ldHnvckBCe3OjeR?= MVy1NFDjiImwTdMg MkP4NVYhcA>? NF\SVo1mdmijbnPld{B1cGViQ2jDUFEzKGSrcnXjeIVlKG2rZ4LheIlwdg>? NUTCenpKOjV4N{[2PVE>
SN179  NV35OZJYTnWwY4Tpc44hSXO|YYm= NUjMUVFNPTBy4pEJcm3DqA>? NH3rNJQyPiCq M4m0[Ilv[3KnYYPld{Bj[XOjbDDtbYdz[XSrb39CpC=> NEDWN2szPTZ5Nk[5NS=>
Jurkat MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYq3NuKhcMLi NGjPUGtIUTVyPUGuOUDDuSByLkKg{txO MVWyOFY5OTJyNR?=
K-562 NXHUWXZ2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkDQO|LDqGkEoB?= NVW2R5FKT0l3ME2xMlghyrFiMD6xJO69VQ>? NYXsWXdvOjR4OEGyNFU>
NCTC-2544 Mnr5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{OxNVczyqCqwrC= NWjUboFwT0l3ME20MlYhyrFiMD6zJO69VQ>? MnHTNlQ3QDF{MEW=
A-431 NXn2XJFtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXLUWWlGPzMEoHlCpC=> Mn70S2k2OD1{LkSgxtEhOC5|IN88US=> MlnGNlQ3QDF{MEW=
SK-N-SH MkLMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV3De25oOC54MkWtNlAh|ryP MoDKOFghcA>? MnjLSG1UVw>? MoXYbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NXraUHY5OjR|OUmwO|Q>
SH-SY5Y NWTob|Y3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIPoPGoxNjZ{NT2yNEDPxE1? MXG0PEBp NVvESox[TE2VTx?= NVPLNY1NcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NVS4XpZqOjR|OUmwO|Q>
SK-N-SH NEL1SItCeG:ydH;zbZNqKEG|c3H5 NF;ie3A2NzFyL{KwJO69VQ>? NVPrN41VPDhiaB?= MYnEUXNQ M2W0U4lv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= MUeyOFM6QTB5NB?=
SH-SY5Y M4L0R2Fxd3C2b4Ppd4khSXO|YYm= NX;TeVRiPS9zMD:yNEDPxE1? MmG2OFghcA>? M2HXNGROW09? MVvpcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 MWmyOFM6QTB5NB?=
SK-N-SH MUHGeY5kfGmxbjDBd5NigQ>? NFj0OZM2NzFyL{KwJO69VQ>? MlXyOFghcA>? Mm\oSG1UVw>? NYHEZ2tIcW6mdXPld{BIOSCyaHHz[UBk\WyuIHP5Z4xmKGG{cnXzeC=> MmLnNlQ{QTlyN{S=
SH-SY5Y M4\tNWZ2dmO2aX;uJGF{e2G7 NWHSTW5MPS9zMD:yNEDPxE1? MoTTOFghcA>? NFe0OGVFVVOR NVraXFM3cW6mdXPld{BIOSCyaHHz[UBk\WyuIHP5Z4xmKGG{cnXzeC=> M4\1fVI1Ozl7MEe0
SK-N-SH MYXGeY5kfGmxbjDBd5NigQ>? MonNNU82NzFyIN88US=> MnPZOFghcA>? M3vIfmROW09? MmTsbY5pcWKrdIOgVmVVKHCqb4PwbI9zgWyjdHnvci=> NFvje|QzPDN7OUC3OC=>
SH-SY5Y M36ySmZ2dmO2aX;uJGF{e2G7 M4\UelEwPS9zMDFOwG0> NVjaUYpuPDhiaB?= NUfsb2kxTE2VTx?= M17rfYlvcGmkaYTzJHJGXCCyaH;zdIhwenmuYYTpc44> MXOyOFM6QTB5NB?=
SK-N-SH NUPUZ4ZXTnWwY4Tpc44hSXO|YYm= MYC1M|ExKM7:TR?= MY[0PEBp NVXMR2p2TE2VTx?= NIjlVpJqdmirYnn0d{BpfW2jbjDORkBk\WyuIH3p[5JifGmxbh?= MYqyOFM6QTB5NB?=
SH-SY5Y MUPGeY5kfGmxbjDBd5NigQ>? NUDCWWRGPS9zMDFOwG0> M{X5dlQ5KGh? MUPEUXNQ NEm0V|dqdmirYnn0d{BpfW2jbjDORkBk\WyuIH3p[5JifGmxbh?= NHXaUnQzPDN7OUC3OC=>
SK-N-SH M1T5W2Z2dmO2aX;uJGF{e2G7 NULkbHdbPS9zMDFOwG0> NWjnc29RPDhiaB?= NYG1bmNGTE2VTx?= MVPpcohq[mm2czDoeY1idiCQQjDj[YxtKGmwdnHzbY9v NGfU[FYzPDN7OUC3OC=>
SH-SY5Y MoL4SpVv[3Srb36gRZN{[Xl? MmT5OU8yOCEQvF2= MXu0PEBp Mor4SG1UVw>? NXLTe28ycW6qaXLpeJMhcHWvYX6gUmIh[2WubDDpcpZie2mxbh?= NVu5d5JPOjR|OUmwO|Q>
SK-N-SH Mn3HSpVv[3Srb36gRZN{[Xl? NF;mbFE2KM7:TR?= MV:yOE81QC95MjDo MmnLSG1UVw>? NWXLfIR4e3WycILld5NmeyC2aHWg[ZhxemW|c3nvckBw\iCFWFPSOEBidmRiTV3QNVQhdVKQQR?= M{nPXlI1Ozl7MEe0
SH-SY5Y MoTySpVv[3Srb36gRZN{[Xl? NW\ucodPPSEQvF2= MXiyOE81QC95MjDo MmHnSG1UVw>? NUXxV5BLe3WycILld5NmeyC2aHWg[ZhxemW|c3nvckBw\iCFWFPSOEBidmRiTV3QNVQhdVKQQR?= MkXSNlQ{QTlyN{S=
SK-N-SH M{X2ZmZ2dmO2aX;uJGF{e2G7 MWq1JO69VQ>? M1zQNVQ5Nzd{IHi= Mn3LSG1UVw>? MoHld5VxeHKnc4Pld{BmgHC{ZYPzbY9vKG:oIITo[UBEYEOUNDDhcoQhVU2SMUSgdJJwfGWrbh?= NGTKU3QzPDN7OUC3OC=>
SH-SY5Y NHXzXWlHfW6ldHnvckBCe3OjeR?= M1;heVUh|ryP NGDRdFI1QC95MjDo NFfsVZBFVVOR NFHafFF{fXCycnXzd4V{KGW6cILld5Nqd25ib3[geIhmKEO[Q2K0JIFv\CCPTWCxOEBxem:2ZXnu NUW4RVdOOjR|OUmwO|Q>
HMEpC Mn3YS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF3nW|IyKG6PLUGwNEDPxE1? M3rGUFQ5yqCqwrC= M2HTemROW09? NXfCcpJpcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MVGyOFE{QDh2Mx?=
MCF-7 NX7Id4JbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnPHNUBvVS1zMECg{txO NF\2Z4Y1QMLiaNMg M4PWS2ROW09? NGW2PY5qdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NVXsTFFHOjRzM{i4OFM>
ZR-75-1 NEjBbnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH3y[lMyKG6PLUGwNEDPxE1? NUfFb4pXPDkEoHlCpC=> NHW4XIVFVVOR NV7vNpVocW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MmTsNlQyOzh6NEO=
MDA-MB-231 M2jNSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmX1NUBvVS1zMECg{txO Ml3oOFjDqGkEoB?= Mmq0SG1UVw>? MlLjbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M1iydFI1OTN6OESz
MDA-MB-468 MnvKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYG5WWUzOSCwTT2xNFAh|ryP MWC0POKhcMLi MnziSG1UVw>? NHnvVZdqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NF\HfYczPDF|OEi0Ny=>
T-47-D NUXDXWNLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWr3bo1oOSCwTT2xNFAh|ryP NXnWSXA5PDkEoHlCpC=> NIW3bmxFVVOR M2rGV4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MorBNlQyOzh6NEO=
U251  Mn;ESpVv[3Srb36gRZN{[Xl? NV7RWmQ1Oi92L{lihKnPxOLGs9Mg NU[zRo9DPi9zMj:yOEBp Mk\ySG1UVw>? NYDWRlNjcW6lcnXhd4V{KHSqZTDMR|MuUUlibHX2[YwhcW5iYTD0bY1mNWSncHXu[IVvfCCjbnSg[I9{\S2mZYDlcoRmdnRibXHucoVz NXfLTpVlOjN5OUm4OVI>
U87MG MlLhSpVv[3Srb36gRZN{[Xl? M3XLflIwPC964pEJ{tzjjLQEoB?= MUS2M|EzNzJ2IHi= M2facWROW09? NHy4V3VqdmO{ZXHz[ZMhfGinIFzDN{1KUSCuZY\lcEBqdiCjIITpcYUu\GWyZX7k[Y51KGGwZDDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> Ml71NlM4QTl6NUK=
U251  NYTzRYNjTnWwY4Tpc44hSXO|YYm= M4nJO|TjiIoQvPMEt:Kh NE\aVYkzNzZxMUKgbC=> NGPjO|FFVVOR M2jpU5N2eHC{ZYPz[ZMh[mG|YXygcIV3\Wy|IH;mJJBpd3OyaH;yfYxifGmxbjDv[kBUPiBqU{KzOU8zOzZrLDC0SU1DWDFiKGSzO{81PiluIHHu[EBCc3RiKGO0O|MqKGmwIHGgeIlu\S2mZYDlcoRmdnRibXHucoVzyqB? M2rzcFI{Pzl7OEWy
U87MG MV3GeY5kfGmxbjDBd5NigQ>? MmK2OQKBkc7:4pUzxsA> M3XJW|IwPi9zMjDo M1nOfWROW09? MmH6d5VxeHKnc4Pld{Bj[XOjbDDs[ZZmdHNib3[gdIhwe3Cqb4L5cIF1cW:wIH;mJHM3KCiVMkO1M|I{PiluIETFMWJROSBqVEO3M|Q3MSxiYX7kJGFsfCBqU{S3N{khcW5iYTD0bY1mNWSncHXu[IVvfCCvYX7u[ZLDqA>? NVLPeW5yOjN5OUm4OVI>
H1650  NGTqVHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVTJR|UxRTNwNdMxNU4zKM7:TR?= MnvlNlMzPzR5NUi=
HUVECs  NGfr[4dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{Sye|czKGh? MkPvTWM2OMLiPTC3MlEh|ryvb3yvUC=> NXTIN5RqOjJ4MUGwNlc>
KYN-2  M3roRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUC3NkBp M{SxdWlEPTEEoE2gPE4yKM7:bX;sM2w> MXeyNlYyOTB{Nx?=
HuH-7  Mlf0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFjXWnU4OiCq MmPlTWM2OMLiPTC5MlQh|ryvb3yvUC=> NFvlVHIzOjZzMUCyOy=>
HUVECs  NU[3cIlXTnWwY4Tpc44hSXO|YYm= NGPPeVgyNzVxMUCg{txO MkfmNUBp NWn6PVlie2mpbnnmbYNidnSueTDpcohq[mm2czDWSWdHWi1{IIDoc5NxcG:{eXzheIlwdg>? MYqyNlYyOTB{Nx?=
HAK1-B MkX2SpVv[3Srb36gRZN{[Xl? MWOxM|UwOTBizszN NWrZbFdYOSCq NFS3VYx{fXCycnXzd4V{KEWJRmKgdIhwe3Cqb4L5cIF1cW:w MWOyNlYyOTB{Nx?=
UM-22A MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYSwMVYh|ryP NHqwW|Q4OiCq MXzEUXNQ M2\oT4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NY\uSIM6OjJ|MEe3N|U>
UM-22B NFPMO|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoHWNE03KM7:TR?= Mnj6O|IhcA>? MV\EUXNQ MmXHbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M3HRcFIzOzB5N{O1
PCI-37A MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NE[4S3ExNTZizszN NUjwPXpPPzJiaB?= MkmySG1UVw>? NVPGdXhocW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MoHKNlI{ODd5M{W=
PCI-37B NHOyN|RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWnlWmVkOC14IN88US=> NXnV[XYyPzJiaB?= NVy5VVQ4TE2VTx?= NUTOWZo5cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NF3qdIIzOjNyN{ezOS=>
PCI-15B M17se2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mk[yNE03KM7:TR?= NWrkXppZPzJiaB?= M1PRVmROW09? NHS3XFVqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M123eFIzOzB5N{O1
SCC-25 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXPjPWV[OC14IN88US=> NFLWb444OiCq MofuSG1UVw>? M17YUIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M{LaVFIzOzB5N{O1
UM-22A MYnGeY5kfGmxbjDBd5NigQ>? MV:wMVExKM7:TR?= NIjRVG4zPCCq NXX3bWtGTE2VTx?= NIi3[GhqdmirYnn0d{B1cGViYXP0bZZifGmxbjDv[kB1cGViRVfGVkB1gXKxc3nu[UBscW6jc3WgZY5lKGGuc3:g[IVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIH;mJJBpd3OyaH;yfYxifGWmIH\vdo1{KG:oIITo[UBld3ewc4Ty[YFuKHOrZ37hcIlv\yCnbHXt[Y51eyxiU2TBWFMh[W6mIF3BVGs> NXfVV3ZSOjJ|MEe3N|U>
UM-22B M1Gwe2Z2dmO2aX;uJGF{e2G7 NYrkUWI6OC1zMDFOwG0> NFn1UpczPCCq NXjkTnN7TE2VTx?= Mo[2bY5pcWKrdIOgeIhmKGGldHn2ZZRqd25ib3[geIhmKEWJRmKgeJlzd3OrbnWgb4lv[XOnIHHu[EBidHOxIHTlZ5Jm[XOnczD0bIUh\XiycnXzd4lwdiCxZjDwbI9{eGixconsZZRm\CCob4Ltd{Bw\iC2aHWg[I94dnO2cnXhcUB{cWewYXzpcoch\WynbXXueJMtKFOWQWSzJIFv\CCPQWDL NGLN[pgzOjNyN{ezOS=>
PCI-15B NIPiPIFHfW6ldHnvckBCe3OjeR?= M3LpUVAuOTBizszN M2r1bFI1KGh? MX\EUXNQ M3SwdYlvcGmkaYTzJJRp\SCjY4TpeoF1cW:wIH;mJJRp\SCHR1\SJJR6em:|aX7lJItqdmG|ZTDhcoQh[Wy|bzDk[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ib3[gdIhwe3Cqb4L5cIF1\WRiZn;ycZMhd2ZidHjlJIRwf26|dILlZY0he2mpbnHsbY5oKGWuZX3lcpR{NCCVVFHUN{BidmRiTVHQTy=> NGjLeowzOjNyN{ezOS=>
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PCI-15B MU\JcpZie2mxbjDBd5NigQ>? MnrsNlQhcA>? NF3zO2FFVVOR NGfYS5pGSzVyPUW1PEBvVQ>? NXG4dol7OjJ|MEe3N|U>
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SCC-25 NHPJTWZKdn[jc3nvckBCe3OjeR?= MWGyOEBp MkDISG1UVw>? Mkn0SWM2OD1zMDDuUS=> MkW5NlI{ODd5M{W=
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201T MVHGeY5kfGmxbjDBd5NigQ>? NUXXW|Z{Oi53IN88US=> NU\jdGJMPDhiaB?= M2XoeWROW09? MlLwbY5pcWKrdIOgdIhwe3Cqbz3NRXBMKG[xbHzve4lv\yCHR1[= NFXrOngzOjJ3OES3Oi=>
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A549 MVXGeY5kfGmxbjDBd5NigQ>? Ml7SNk42KM7:TR?= NFXZPWs1QCCq MlXaSG1UVw>? NUX2PIdKcW6qaXLpeJMheGixc4Doc{1OSVCNIH\vcIxwf2mwZzDFS2Y> NYDzV2E4OjJ{NUi0O|Y>
201T  NF7ne2xHfW6ldHnvckBCe3OjeR?= M3n5blEwPS9zMDFOwG0> NVjQZ2lSPDhiaB?= NGKyNVdFVVOR M3zwOIJtd2OtczD0bIUheGixc4Doc5J6dGG2aX;uJI9nKEGtdDDpcoR2[2WmIHL5JHZGT0[F MVyyNlI2QDR5Nh?=
H2052 NHHTRo9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2jRWmlEPTB;MT6wO:KyOC5yNDFOwG0> NIDDblAzOTl5MEi3OC=>
H2452 NVW4ZnZCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{PYTGlEPTB;Mz61NuKyOS5zMzFOwG0> MWiyNVk4ODh5NB?=
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MSTO-211H MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYDJR|UxRTFwNENCtVAvODNizszN MlXpNlE6PzB6N{S=
Hth83 M{HMWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIn2Z3c4OiCq M33jZmROW09? MYrJR|UxRTNwM{CgxtEhOC54NjFOwG0> M1vYblIyOjJyNEe3
C643 M3T3UGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVS3NkBp M1rtN2ROW09? MV7JR|UxRTNwNkWgxtEhOS5{MjFOwG0> MX6yNVIzODR5Nx?=
8505C Ml3NS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFH5TWQ4OiCq NVizWm9[TE2VTx?= NHvmbY1KSzVyPUeuOVYhyrFiMT6xN{DPxE1? NISw[JkzOTJ{MES3Oy=>
Hth74 NHzCepRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWC3NkBp M1uwVGROW09? MmG2TWM2OD16LkW2JOKyKDFwMEGg{txO MXKyNVIzODR5Nx?=
SW1736 NF23emhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWXqPXM{PzJiaB?= NXTmZmRsTE2VTx?= NH[yU2VKSzVyPUmuNFUhyrFiMD61OUDPxE1? NYHXUVY4OjF{MkC0O|c>
Hth7 M{C1[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3;mc|czKGh? M3LWdWROW09? MmHXTWM2OD17Lk[2JOKyKDBwM{ig{txO Mn\rNlEzOjB2N{e=
Hth104 NYnwU2djT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3XNNlczKGh? M2jDeWROW09? M{C0WGlEPTB;wsGxOk46QCEEsTDORUDPxE1? NFniVJQzOTJ{MES3Oy=>
HTB3 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVSwMVIxKM7:TR?= NWD6c4pUOjUEoHi= NXzEeG06cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MnPsNVkzOjB{NU[=
HT1376 NUXEdIozT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHnvd5oxNTJyIN88US=> NXzrPHU1OjUEoHi= NEf0eYlqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M3HiRlE6OjJyMkW2
RT4 NEDVdZdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH7B[ZcxNTJyIN88US=> MnrWNlTDqGh? NW\ue|BQcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MkPJNVkzOjB{NU[=
J82 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXjHOVFZOC1{MDFOwG0> M{\mbFI1yqCq NXHhephDcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NHPvRokyQTJ{MEK1Oi=>
CRL1749 NX;uWGxlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1TFVVAuOjBizszN MlfiNlTDqGh? M1fwOolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MWGxPVIzODJ3Nh?=
T24 M37qZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3nuOVAuOjBizszN M4HOfFI1yqCq M3jyWIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MXSxPVIzODJ3Nh?=
SUP MoDUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUWwMVIxKM7:TR?= MnvRNlTDqGh? NUnZTHZvcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M{LtWFE6OjJyMkW2
HTB9 NHmxSHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3zaeVAuOjBizszN NVLxbVNYOjUEoHi= M4PYc4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NWPMV3J5OTl{MkCyOVY>
ACC3 NUjobox[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEHCS3kxNTFyIN88US=> NViwTXlWPzJiaB?= M{\BVYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MojhNVg3QThyMkW=
ACC2 M1y2T2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXnFRVNnOC1zMDFOwG0> MnPNO|IhcA>? MVXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NUTid|VFOTh4OUiwNlU>
ACCM NU\SNYxST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnrJNE0yOCEQvF2= MonzO|IhcA>? M4K5UYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NYXse2VIOTh4OUiwNlU>
ACC3 MXvBdI9xfG:|aYPpJGF{e2G7 NX[1dIxkOC1zMDFOwG0> NF7LdlY4OiCq M1HjXYlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= NYmzR|RmOTh4OUiwNlU>
ACC2 M2\R[mFxd3C2b4Ppd4khSXO|YYm= M4i5elAuOTBizszN MkH2O|IhcA>? NHjoeHFqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 M3PHTFE5Pjl6MEK1
ACCM NHXSeVFCeG:ydH;zbZNqKEG|c3H5 Mlr5NE0yOCEQvF2= MoDqO|IhcA>? M33VN4lv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= M3HwelE5Pjl6MEK1
EHMES-1 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1rUT|czKGh? NVfDVYh7TE2VTx?= NYi5Zm01UUN3ME2xNE43KM7:TR?= MojRNVg{PjR{NEi=
EHMES-10 M3vUWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGToO4I4OiCq NXnBVY03TE2VTx?= MorBTWM2OD1yLkOg{txO NF3JTVcyQDN4NEK0PC=>
211H NFvrPZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXfYUGRYPzJiaB?= NWnnXpg{TE2VTx?= NGe5UGpKSzVyPUKuNkDPxE1? NFL2Zo8yQDN4NEK0PC=>
H28 NYf3UoR{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1vUSVczKGh? MVHEUXNQ M1zWU2lEPTB;MT64JO69VQ>? MmrKNVg{PjR{NEi=
H2052 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVS3NkBp M33ad2ROW09? MX;JR|UxRThwMDFOwG0> MVuxPFM3PDJ2OB?=
H2452 NX76WlN4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4rPUFczKGh? NWLybXNPTE2VTx?= MmfGTWM2OD13LkWg{txO NF;GbW4yQDN4NEK0PC=>
CNE-1 MoXGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWGwMlEuOjVwNjFOwG0> NHO2c2c1QCCq Mn71TWM2OD1|Lk[g{txO NXfJVG41OTd4M{G2OFY>
CNE-2 NXjyWpN3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV3rS4JKOC5zLUK1MlYh|ryP NVnaV5VUPDhiaB?= NFrOcVdKSzVyPU[uNkDPxE1? NWDEWI1COTd4M{G2OFY>
C666-1 M1;u[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGS3elMxNjFvMkWuOkDPxE1? MU[0PEBp MUPJR|UxRTJ|LkSg{txO M3XITFE4PjNzNkS2
CNE-1 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn3WNE4yNTJ3Lk[g{txO MWe3NkBp MVLJR|UxRTJwMzFOwG0> NHjpTXAyPzZ|MU[0Oi=>
CNE-2 NF;Mem5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3PKb|AvOS1{NT62JO69VQ>? MWK3NkBp NFf2fFhKSzVyPUOuOkDPxE1? M2Xqc|E4PjNzNkS2
C666-1 NFX0eYJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHHsOIQxNjFvMkWuOkDPxE1? M1X4VVczKGh? NV\1[npWUUN3ME20Mlg3KM7:TR?= NHftb|EyPzZ|MU[0Oi=>
CNE-1 NUPvcZBbTnWwY4Tpc44hSXO|YYm= M2HFelYh|ryP NWfoV|AyOjRiaB?= MWDk[YxigXNiR{CvS|Eh[2WubDDjfYNt\SCycn;ndoV{e2mxbh?= NFnqSY8yPzZ|MU[0Oi=>
CNE-2 Mn;HSpVv[3Srb36gRZN{[Xl? MVy2JO69VQ>? MWmyOEBp Mn7q[IVt[Xm|IFewM2cyKGOnbHygZ5lkdGVicILv[5Jme3Orb36= NYLqc2lpOTd4M{G2OFY>
C666-1 M3HDVGZ2dmO2aX;uJGF{e2G7 NInxeYY3KM7:TR?= M{WwRlI1KGh? MYLk[YxigXNiR{CvS|Eh[2WubDDjfYNt\SCycn;ndoV{e2mxbh?= NHT6XWQyPzZ|MU[0Oi=>

... Click to View More Cell Line Experimental Data

In vivo Vandetanib (2.5 mg/kg, i.v.), reverses a VEGF-induced hypotension by 63% but does not significantly affect a bFGF-induced hypotension. Vandetanib (100 mg/kg) inhibits the tumor-induced blood vessel formation by 79%. Vandetanib (12.5-100 mg/kg, orally) shows great tumor growth inhibition in human tumor xenografts including Calu-6, PC-3, MDA-MA-231, SKOV-3, SW620, A549, A431, B16-F10(AP3) and Lewis Lung, with little effects on body weight. [1] In PC3wt xenografts, administration of Vandetanib alone exerts paradoxical tumor growth stimulating effects. In PC3R xenografts, the low dose of Vandetanib (25 mg/kg) has no significant effect relative to control, whereas the high dose (50 mg/kg) significantly inhibits tumor growth compared with control. In contrast, the high-dose combination reveals a significant negative interaction between Vandetanib 50 mg/kg and docetaxel 30 mg/kg in PC3R cells. [3] In tumor-bearing mice, Vandetanib suppresses phosphorylation of VEGFR2 and EGFR in tumor tissues, significantly decreases tumor vessel density, enhances tumor cell apoptosis, suppresses tumor growth, improves survival, reduces number of intrahepatic metastases, and up-regulates VEGF, TGF-alpha and EGF in tumor tissues. Treatment with Vandetanib is not associated with serious adverse events, including ALT abnormality, bone marrow suppression or body weight loss. [4] Vandetanib treatment of nude mice bearing palpable GEO colon cancer xenografts (which are sensitive to inhibition of EGFR signaling) induces dose-dependent tumor growth inhibition. [5]

Protocol

Kinase Assay:

[1]

+ Expand

Kinase inhibition:

Vandetanib is incubated with enzyme, 10 mM MnCl2, and 2 μM ATP in 96-well plates coated with a poly(Glu, Ala, Tyr) 6:3:1 random copolymer substrate. Phosphorylated tyrosine is then detected by sequential incubation with a mouse IgG anti-phosphotyrosine 4G10 antibody, a horseradish peroxidase-linked sheep antimouse immunoglobulin antibody, and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid). This methodology is adapted to examine selectivity versus tyrosine kinases associated with EGFR, PDGFRβ, Tie-2, FGFR1, c-kit, erbB2, IGF-1R, and FAK. All enzyme assays (tyrosine or serine-threonine) used appropriate ATP concentrations at or just below the respective Km (0.2–14 μM). Selectivity versus serine-threonine kinases (CDK2, AKT, and PDK1) is examined using a relevant scintillation proximity-assay (SPA) in 96-well plates. CDK2 assays contained 10 mM MnCl2, 4.5 μM ATP, 0.15 μCi of [γ-33 P]ATP/reaction, 50 mM HEPES (pH 7.5), 1 mM DTT, 0.1 mM sodium orthovanadate, 0.1 mM sodium fluoride, 10 mM sodium glycerophosphate, 1 mg/mL BSA fraction V, and a retinoblastoma substrate (part of the retinoblastoma gene, 792–928, expressed in a glutathione S-transferase expression system; 0.22 μM final concentration). Reactions are allowed to proceed at room temperature for 60 minutes before quenching for 2 hours with 150 μL of a solution containing EDTA (62 mM final concentration), 3 μg of a rabbit immunoglobulin anti-glutathione S-transferase antibody and protein A SPA-polyvinyltoluene beads (0.8 mg/reaction). Plates are then sealed, centrifuged (1200× g for 5 minutes), and counted on a Microplate scintillation counter for 30 seconds.
Cell Research:

[1]

+ Expand
  • Cell lines: Calu-6, PC-3, MDA-MA-231, SKOV-3, SW620, A549, A431, B16-F10(AP3) and Lewis Lung cells
  • Concentrations: 0.1–100 μM
  • Incubation Time: 72 hours
  • Method:

    Tumor cells are plated in their respective media at predetermined densities that are known to enable logarithmic cell growth during the period of assay (PC-3, 500 cells/well; all others, 1000 cells/well). Plates are incubated for 24 hours (37 °C with CO2) before the addition of Vandetanib (0.1–100 μM) or vehicle (0.1% DMSO in medium). Plates are reincubated for an additional 72 hours before assessing cell proliferation by [3 H]thymidine incorporation by a beta counter.


    (Only for Reference)
Animal Research:

[5]

+ Expand
  • Animal Models: Female athymic (nu/nu genotype) Swiss mice with PC-3, Calu-6, SKOV-3, and MDA-MB-231 tumors
  • Formulation: 1% (v/v) solution of polyoxyethylene
  • Dosages: 12.5 mg/kg/day, 25 mg/kg/day, 50 mg/kg/day, or 100 mg/kg/day
  • Administration: Oral administration
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 4 mg/mL (8.41 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents individually and in order:
1% CMC Na
30mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 475.35
Formula

C22H24BrFN4O2

CAS No. 443913-73-3
Storage powder
Synonyms N/A

Bio Calculators

Molarity Calculator

Molarity Calculator

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

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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

Dilution Calculator

Dilution Calculator

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

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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The Serial Dilution Calculator Equation

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  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
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    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
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    C8=C7/X C8: LOG(C8):
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
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