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  NGrWRWxHfW6ldHnvckBCe3OjeR?= NGS1Tlc2ODEkgJnuUeKh M2XLVVE3KGh? MXjpcoNz\WG|ZYOgR3hEWjRiZYjwdoV{e2mxbjDzbYdvcW[rY3HueIx6 M1TtVlI2Pjd4Nkmx
SN186 NVS3NFV7TnWwY4Tpc44hSXO|YYm= NXzrRmNvPTBy4pEJcm3DqA>? NVjFZpQ6OTZiaB?= NG\Eco5qdmO{ZXHz[ZMhS1iFUkSg[ZhxemW|c3nvckB{cWewaX\pZ4FvfGy7 M1TUcVI2Pjd4Nkmx
SN179  M3rKS2Z2dmO2aX;uJGF{e2G7 MVO1NFDjiImwTdMg NVjVSXVVOTZiaB?= M{\MVIVvcGGwY3XzJJRp\SCFWFPMNVIh\Gm{ZXP0[YQhdWmpcnH0bY9v M{PzeVI2Pjd4Nkmx
SN179  M{fSe2Z2dmO2aX;uJGF{e2G7 NGrMVIU2ODEkgJnuUeKh MYSxOkBp NEm4fYtqdmO{ZXHz[ZMh[mG|YXygcYloemG2aX;uxsA> MXuyOVY4PjZ7MR?=
Jurkat NFXxTpZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIP2T|k4OsLiaNMg NFGze2FIUTVyPUGuOUDDuSByLkKg{txO NUTz[nQzOjR4OEGyNFU>
K-562 NFfWSGdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2XtW|czyqCqwrC= NFT6fWpIUTVyPUGuPEDDuSByLkGg{txO Ml6xNlQ3QDF{MEW=
NCTC-2544 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIS3dpM4OsLiaNMg M1LGbGdKPTB;ND62JOKyKDBwMzFOwG0> M3nUSFI1PjhzMkC1
A-431 NETiXXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEPjb4I4OsLiaNMg MVjHTVUxRTJwNDFCtUAxNjNizszN MlzsNlQ3QDF{MEW=
SK-N-SH NHXJXm1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVOwMlYzPS1{MDFOwG0> M3vifFQ5KGh? MoGzSG1UVw>? NHXTXFFqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NX;UVXpVOjR|OUmwO|Q>
SH-SY5Y NH\pXolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFXDbI4xNjZ{NT2yNEDPxE1? MWe0PEBp MUPEUXNQ MkX2bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NXnWZ|dMOjR|OUmwO|Q>
SK-N-SH MVfBdI9xfG:|aYPpJGF{e2G7 MlXmOU8yOC9{MDFOwG0> MWK0PEBp MkP5SG1UVw>? NFXxTYtqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 M{HWSVI1Ozl7MEe0
SH-SY5Y MnrNRZBweHSxc3nzbUBCe3OjeR?= NFXqV402NzFyL{KwJO69VQ>? MYm0PEBp MmLkSG1UVw>? NH;vWVZqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 M17zSlI1Ozl7MEe0
SK-N-SH NUHlcFZYTnWwY4Tpc44hSXO|YYm= NETNW4c2NzFyL{KwJO69VQ>? MVm0PEBp NETaUIVFVVOR MUXpcoR2[2W|IFexJJBp[XOnIHPlcIwh[3mlbHWgZZJz\XO2 M1Ltb|I1Ozl7MEe0
SH-SY5Y NVS5SIpKTnWwY4Tpc44hSXO|YYm= NWHtTGdWPS9zMD:yNEDPxE1? MUS0PEBp M3zyXGROW09? Mn3YbY5lfWOnczDHNUBxcGG|ZTDj[YxtKGO7Y3zlJIFzemW|dB?= M2DjN|I1Ozl7MEe0
SK-N-SH NULQZm1ETnWwY4Tpc44hSXO|YYm= NH;vPWMyNzVxMUCg{txO NEPlPXY1QCCq Ml7JSG1UVw>? NYDoWVZYcW6qaXLpeJMhWkWWIIDoc5NxcG:{eXzheIlwdg>? MWOyOFM6QTB5NB?=
SH-SY5Y MV3GeY5kfGmxbjDBd5NigQ>? NGTOTYoyNzVxMUCg{txO NHjIbGg1QCCq NXjDNVdOTE2VTx?= MnT1bY5pcWKrdIOgVmVVKHCqb4PwbI9zgWyjdHnvci=> NG\BZlgzPDN7OUC3OC=>
SK-N-SH MkC4SpVv[3Srb36gRZN{[Xl? NVrRd25DPS9zMDFOwG0> MnTtOFghcA>? M4fuZmROW09? NFPGUWxqdmirYnn0d{BpfW2jbjDORkBk\WyuIH3p[5JifGmxbh?= NXK5VlRLOjR|OUmwO|Q>
SH-SY5Y MYrGeY5kfGmxbjDBd5NigQ>? NETnd242NzFyIN88US=> M{SzelQ5KGh? NGLkco5FVVOR NGSw[|NqdmirYnn0d{BpfW2jbjDORkBk\WyuIH3p[5JifGmxbh?= NUTpd21mOjR|OUmwO|Q>
SK-N-SH NYC2OHB3TnWwY4Tpc44hSXO|YYm= MWS1M|ExKM7:TR?= M{PuRlQ5KGh? NULrUo5wTE2VTx?= MVvpcohq[mm2czDoeY1idiCQQjDj[YxtKGmwdnHzbY9v NYTYOmxrOjR|OUmwO|Q>
SH-SY5Y NED5bWdHfW6ldHnvckBCe3OjeR?= MWW1M|ExKM7:TR?= NXzNdXBDPDhiaB?= NFvnW|VFVVOR M3fuWolvcGmkaYTzJIh2dWGwIF7CJINmdGxiaX72ZZNqd25? M2e1PVI1Ozl7MEe0
SK-N-SH NXHCXVMyTnWwY4Tpc44hSXO|YYm= MnLwOUDPxE1? MmnnNlQwPDhxN{KgbC=> M4rMPGROW09? M3vzfZN2eHC{ZYPz[ZMhfGinIHX4dJJme3Orb36gc4YhS1iFUkSgZY5lKE2PUEG0JI1TVkF? MmDUNlQ{QTlyN{S=
SH-SY5Y NEHGVG9HfW6ldHnvckBCe3OjeR?= NYnyNo9{PSEQvF2= NVjWbWVkOjRxNEivO|IhcA>? M1PDO2ROW09? NX3Yfnhje3WycILld5NmeyC2aHWg[ZhxemW|c3nvckBw\iCFWFPSOEBidmRiTV3QNVQhdVKQQR?= NIrBcHkzPDN7OUC3OC=>
SK-N-SH Mkm3SpVv[3Srb36gRZN{[Xl? NE\VWlk2KM7:TR?= MlPYOFgwPzJiaB?= MoriSG1UVw>? M{DXT5N2eHC{ZYPz[ZMh\XiycnXzd4lwdiCxZjD0bIUhS1iFUkSgZY5lKE2PUEG0JJBzd3SnaX6= M2HlRlI1Ozl7MEe0
SH-SY5Y M3HOfGZ2dmO2aX;uJGF{e2G7 M3zHclUh|ryP NGfCdGc1QC95MjDo NEjh[|JFVVOR NVHiRlFoe3WycILld5NmeyCneIDy[ZN{cW:wIH;mJJRp\SCFWFPSOEBidmRiTV3QNVQheHKxdHXpci=> NYH5[5lYOjR|OUmwO|Q>
HMEpC M1HrSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1zQTVEhdk1vMUCwJO69VQ>? NFy3VmY1QMLiaNMg MlfySG1UVw>? NV7pSWRKcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NWLncnplOjRzM{i4OFM>
MCF-7 M{XiV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{G5cFEhdk1vMUCwJO69VQ>? MUO0POKhcMLi MWnEUXNQ MojHbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NYCxbHFSOjRzM{i4OFM>
ZR-75-1 MoPES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4jDXFEhdk1vMUCwJO69VQ>? M{nuc|Q5yqCqwrC= M1X3U2ROW09? NGjx[ZdqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MkfLNlQyOzh6NEO=
MDA-MB-231 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVqxJI5ONTFyMDFOwG0> NFK4doM1QMLiaNMg NWXZNGxuTE2VTx?= NIHYNXRqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NGrCV4IzPDF|OEi0Ny=>
MDA-MB-468 MkX3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2m2c|Ehdk1vMUCwJO69VQ>? M2XTSlQ5yqCqwrC= MX3EUXNQ NYi1R4locW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MoLDNlQyOzh6NEO=
T-47-D MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXuxJI5ONTFyMDFOwG0> M1XOd|Q5yqCqwrC= MULEUXNQ MmDibY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MoHJNlQyOzh6NEO=
U251  NGDqZpBHfW6ldHnvckBCe3OjeR?= NUDx[mFLOi92L{lihKnPxOLGs9Mg MVm2M|EzNzJ2IHi= M1zVfWROW09? MWfpcoNz\WG|ZYOgeIhmKEyFMz3JTUBt\X[nbDDpckBiKHSrbXWt[IVx\W6mZX70JIFv\CCmb4PlMYRmeGWwZHXueEBu[W6wZYK= NGDEPYwzOzd7OUi1Ni=>
U87MG Mli1SpVv[3Srb36gRZN{[Xl? MXOyM|QwQOLCid885qS{yqB? NFLNPYI3NzF{L{K0JIg> Mn[3SG1UVw>? NGfYNI1qdmO{ZXHz[ZMhfGinIFzDN{1KUSCuZY\lcEBqdiCjIITpcYUu\GWyZX7k[Y51KGGwZDDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> MkPsNlM4QTl6NUK=
U251  Mn:3SpVv[3Srb36gRZN{[Xl? NWewd5ZGPOLCid885qS{yqB? NHjVUYMzNzZxMUKgbC=> M1y4TmROW09? NFq1SGZ{fXCycnXzd4V{KGKjc3HsJIxmfmWuczDv[kBxcG:|cHjvdplt[XSrb36gc4YhWzZiKGOyN|UwOjN4KTygOGUuSlBzIDjUN|cwPDZrLDDhcoQhSWu2IDjTOFc{MSCrbjDhJJRqdWVvZHXw[Y5l\W62IH3hco5mesLi MViyN|c6QTh3Mh?=
U87MG NYr3T2cxTnWwY4Tpc44hSXO|YYm= MkT0OQKBkc7:4pUzxsA> M1zWfVIwPi9zMjDo M{HhfGROW09? NYjxPWdWe3WycILld5NmeyCkYYPhcEBt\X[nbIOgc4YheGixc4Doc5J6dGG2aX;uJI9nKFN4IDjTNlM2NzJ|NjmsJFRGNUKSMTCoWFM4NzR4KTygZY5lKEGtdDCoV|Q4OyliaX6gZUB1cW2nLXTldIVv\GWwdDDtZY5v\XMEoB?= NXfaco9{OjN5OUm4OVI>
H1650  MoTTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVLD[2NEUUN3ME2zMlXDuTFwMjFOwG0> MmrrNlMzPzR5NUi=
HUVECs  MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFv5N4U4OiCq MnHETWM2OMLiPTC3MlEh|ryvb3yvUC=> M1TyUVIzPjFzMEK3
KYN-2  MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NW\VRmtXPzJiaB?= MWrJR|UxyqB;IEiuNUDPxG2xbD;M MWeyNlYyOTB{Nx?=
HuH-7  MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYW3NkBp NGe5VIJKSzVywrC9JFkvPCEQvH3vcE9N M{K2PVIzPjFzMEK3
HUVECs  MYTGeY5kfGmxbjDBd5NigQ>? NF\TSVgyNzVxMUCg{txO NGm4XocyKGh? M{ThfZNq\26rZnnjZY51dHliaX7obYJqfHNiVlXHSnIuOiCyaH;zdIhwenmuYYTpc44> NVu3S4xuOjJ4MUGwNlc>
HAK1-B MnzWSpVv[3Srb36gRZN{[Xl? MYWxM|UwOTBizszN M{HqNVEhcA>? NWHmfmxve3WycILld5NmeyCHR1\SJJBpd3OyaH;yfYxifGmxbh?= MkLTNlI3OTFyMke=
UM-22A NH73SIFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFPFPWUxNTZizszN MnnEO|IhcA>? M4TESWROW09? MknqbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MYqyNlMxPzd|NR?=
UM-22B NWnzd2xGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn72NE03KM7:TR?= M3HnblczKGh? Ml;wSG1UVw>? NFjGWYxqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M1nDfFIzOzB5N{O1
PCI-37A MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NE\UXm4xNTZizszN NHnzOVM4OiCq NUjaPVRVTE2VTx?= NEXM[GZqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MWGyNlMxPzd|NR?=
PCI-37B NFTicmVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXSwMVYh|ryP MX[3NkBp NIPTfGZFVVOR MnPPbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MmLhNlI{ODd5M{W=
PCI-15B M3;qXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH3HflcxNTZizszN MnzBO|IhcA>? NVz2cVhiTE2VTx?= M2TYWYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MXeyNlMxPzd|NR?=
SCC-25 M2PQb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHzTVGExNTZizszN MYG3NkBp MUfEUXNQ MXvpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NXnqbo9IOjJ|MEe3N|U>
UM-22A M{PuVWZ2dmO2aX;uJGF{e2G7 M3ToclAuOTBizszN MUCyOEBp MXzEUXNQ MVPpcohq[mm2czD0bIUh[WO2aY\heIlwdiCxZjD0bIUhTUeIUjD0fZJwe2mwZTDrbY5ie2ViYX7kJIFte29iZHXjdoVie2W|IITo[UBmgHC{ZYPzbY9vKG:oIIDoc5NxcG:{eXzheIVlKG[xcn3zJI9nKHSqZTDkc5dve3S{ZXHtJJNq\26jbHnu[{BmdGWvZX70d{whW1SDVEOgZY5lKE2DUFu= M13DSFIzOzB5N{O1
UM-22B MorwSpVv[3Srb36gRZN{[Xl? MWiwMVExKM7:TR?= MWiyOEBp Mor3SG1UVw>? NX\GNI1GcW6qaXLpeJMhfGinIHHjeIl3[XSrb36gc4YhfGinIFXHSnIhfHm{b4PpcoUhc2mwYYPlJIFv\CCjbIPvJIRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDv[kBxcG:|cHjvdplt[XSnZDDmc5JueyCxZjD0bIUh\G:5boP0doVidSC|aXfuZYxqdmdiZXzlcYVvfHNuIGPURXQ{KGGwZDDNRXBM MV6yNlMxPzd|NR?=
PCI-15B M136U2Z2dmO2aX;uJGF{e2G7 NFfqfFUxNTFyIN88US=> NFPBSIkzPCCq M3uyN2ROW09? NWTCWGl[cW6qaXLpeJMhfGinIHHjeIl3[XSrb36gc4YhfGinIFXHSnIhfHm{b4PpcoUhc2mwYYPlJIFv\CCjbIPvJIRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDv[kBxcG:|cHjvdplt[XSnZDDmc5JueyCxZjD0bIUh\G:5boP0doVidSC|aXfuZYxqdmdiZXzlcYVvfHNuIGPURXQ{KGGwZDDNRXBM Ml\QNlI{ODd5M{W=
PCI-37A NX[weIJKTnWwY4Tpc44hSXO|YYm= NYHLWZhZOSEQvF2= NFq4SGkzPCCq MmWzSG1UVw>? MV3kc5dvemWpdXzheIV{KF[HR1[gdJJw\HWldHnvci=> MkSxNlI{ODd5M{W=
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PCI-15B NIrlNldHfW6ldHnvckBCe3OjeR?= MlLsNUDPxE1? NHfQPIwzPCCq NF61PVRFVVOR NGTmbYdld3ewcnXneYxifGW|IG\FS2YheHKxZIXjeIlwdg>? MmPhNlI{ODd5M{W=
PCI-15B NX;l[YRiUW64YYPpc44hSXO|YYm= NUXCWGNOOjRiaB?= NHz6elhFVVOR MmjESWM2OD13NUigcm0> NXrkWIhOOjJ|MEe3N|U>
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201T Mn;LSpVv[3Srb36gRZN{[Xl? M1r5dFIvPSEQvF2= NUP4bXJjPDhiaB?= MVzEUXNQ MmH2bY5pcWKrdIOgdIhwe3Cqbz3NRXBMKG[xbHzve4lv\yCHR1[= NYTZSmxvOjJ{NUi0O|Y>
273T  M1m5WGZ2dmO2aX;uJGF{e2G7 Ml7tNk42KM7:TR?= MYK0PEBp NXvqWVNsTE2VTx?= MUPpcohq[mm2czDwbI9{eGixLV3BVGsh\m:ubH;3bY5oKEWJRh?= MkW2NlIzPTh2N{[=
A549 NIr3bVNHfW6ldHnvckBCe3OjeR?= NUjWVlk1Oi53IN88US=> MUC0PEBp MUHEUXNQ NITZfnJqdmirYnn0d{BxcG:|cHjvMW1CWEtiZn;scI94cW6pIFXHSi=> M1j5[|IzOjV6NEe2
201T  NF:we4JHfW6ldHnvckBCe3OjeR?= NFfxSnoyNzVxMUCg{txO MXq0PEBp NHTrVnNFVVOR M4fVTIJtd2OtczD0bIUheGixc4Doc5J6dGG2aX;uJI9nKEGtdDDpcoR2[2WmIHL5JHZGT0[F Mnz1NlIzPTh2N{[=
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MSTO-211H M{TQWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWS4bIJuUUN3ME2xMlQzyrFyLkCzJO69VQ>? NHLhdHkzOTl5MEi3OC=>
Hth83 NUXzdWVMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWi3NkBp M3PHZWROW09? MWHJR|UxRTNwM{CgxtEhOC54NjFOwG0> NIm3VGUzOTJ{MES3Oy=>
C643 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWK3NkBp MkXHSG1UVw>? MnyxTWM2OD1|Lk[1JOKyKDFwMkKg{txO M2LUdVIyOjJyNEe3
8505C NIixbnJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX63NkBp NITKVVVFVVOR MWXJR|UxRTdwNU[gxtEhOS5zMzFOwG0> NWPVS4dbOjF{MkC0O|c>
Hth74 MoTrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUe4Z3Z6PzJiaB?= MVLEUXNQ NYnTRoNSUUN3ME24MlU3KMLzIEGuNFEh|ryP NYf2V4JHOjF{MkC0O|c>
SW1736 M2TseGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVS3NkBp NHfvVYhFVVOR NUTlPVYxUUN3ME25MlA2KMLzIECuOVUh|ryP MWqyNVIzODR5Nx?=
Hth7 NV21fmxOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYO3NkBp NH;obYlFVVOR MWTJR|UxRTlwNk[gxtEhOC5|ODFOwG0> MY[yNVIzODR5Nx?=
Hth104 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml[xO|IhcA>? NH3wc5NFVVOR M4r6dWlEPTB;wsGxOk46QCEEsTDORUDPxE1? MVuyNVIzODR5Nx?=
HTB3 M3W4fWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NILuenIxNTJyIN88US=> M3zvTlI1yqCq NE\PcoRqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NIrFWJcyQTJ{MEK1Oi=>
HT1376 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIn3PVcxNTJyIN88US=> NU\5ZpBxOjUEoHi= MoDSbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M1W4SFE6OjJyMkW2
RT4 Mkf6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWSwTZhYOC1{MDFOwG0> Ml;ONlTDqGh? MYnpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NEjiUWwyQTJ{MEK1Oi=>
J82 NXPjUmRFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUTCW|k5OC1{MDFOwG0> M3[1[FI1yqCq M1vBfYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MVKxPVIzODJ3Nh?=
CRL1749 M2e4d2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4fETFAuOjBizszN MYKyOOKhcA>? M4TNdolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NYnKTlFjOTl{MkCyOVY>
T24 NETnXI1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3PQeVAuOjBizszN MWSyOOKhcA>? M{j1N4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NEjEdVAyQTJ{MEK1Oi=>
SUP NIHs[XBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{LWXFAuOjBizszN NYXnUIlbOjUEoHi= M1rr[YlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MXGxPVIzODJ3Nh?=
HTB9 NGTkVYNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmG5NE0zOCEQvF2= M{LoV|I1yqCq MWnpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NE\5cVQyQTJ{MEK1Oi=>
ACC3 NGTVbW1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYCwMVExKM7:TR?= M{i4elczKGh? NULhfIg6cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M{i3O|E5Pjl6MEK1
ACC2 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVz5bWpQOC1zMDFOwG0> MW[3NkBp M3fZb4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MV6xPFY6QDB{NR?=
ACCM NVjh[G54T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUCwMVExKM7:TR?= NH3BWZE4OiCq MmnJbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NYHTPVdMOTh4OUiwNlU>
ACC3 MWTBdI9xfG:|aYPpJGF{e2G7 M1z4S|AuOTBizszN MnLzO|IhcA>? NV3YTVBTcW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> M16zNFE5Pjl6MEK1
ACC2 MYjBdI9xfG:|aYPpJGF{e2G7 M1nsTVAuOTBizszN NYfxUXNbPzJiaB?= NEG5V|FqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 MlPNNVg3QThyMkW=
ACCM NXzCSoFQSXCxcITvd4l{cSCDc4PhfS=> M3PtUVAuOTBizszN NFfPcGE4OiCq M1KxdYlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= NEPHNYgyQDZ7OECyOS=>
EHMES-1 MkHyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVzlNIs{PzJiaB?= NWK4RWdqTE2VTx?= MYTJR|UxRTFyLk[g{txO MVmxPFM3PDJ2OB?=
EHMES-10 M4S3cWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3zL[FczKGh? MVnEUXNQ NHLxWmZKSzVyPUCuN{DPxE1? MWCxPFM3PDJ2OB?=
211H M3j6dWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV23NkBp NIDqdVZFVVOR NIPNb|hKSzVyPUKuNkDPxE1? NV7yNVhlOTh|NkSyOFg>
H28 NXTL[29GT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NE\KdGI4OiCq MoHySG1UVw>? NVzvZY5SUUN3ME2xMlgh|ryP MkHsNVg{PjR{NEi=
H2052 MoC3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUO3NkBp NYD6N2FyTE2VTx?= NE\le|RKSzVyPUiuNEDPxE1? NGnoTZEyQDN4NEK0PC=>
H2452 M4DZR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXG3NkBp NHvGdpdFVVOR Mnr5TWM2OD13LkWg{txO Mnm1NVg{PjR{NEi=
CNE-1 NWezVmdFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVzkUm43OC5zLUK1MlYh|ryP MY[0PEBp NWmzW5lrUUN3ME2zMlYh|ryP NXvGPZRuOTd4M{G2OFY>
CNE-2 NGP3bHNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV;oSnpzOC5zLUK1MlYh|ryP MV60PEBp NVfWTVdlUUN3ME22MlIh|ryP MXyxO|Y{OTZ2Nh?=
C666-1 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWHvXWh1OC5zLUK1MlYh|ryP NWXNdYtyPDhiaB?= M1K3UGlEPTB;MkOuOEDPxE1? NULOUo5sOTd4M{G2OFY>
CNE-1 NX:2Xm9IT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF7qZXMxNjFvMkWuOkDPxE1? MnqyO|IhcA>? MoTXTWM2OD1{LkOg{txO NIH2PWIyPzZ|MU[0Oi=>
CNE-2 NX3uWJNMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVWwMlEuOjVwNjFOwG0> M1XUNFczKGh? NWTXOmZKUUN3ME2zMlYh|ryP MlPsNVc3OzF4NE[=
C666-1 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmLKNE4yNTJ3Lk[g{txO M1\MbVczKGh? MXLJR|UxRTRwOE[g{txO M4XEfVE4PjNzNkS2
CNE-1 NGDERpVHfW6ldHnvckBCe3OjeR?= NFPPfVE3KM7:TR?= MXGyOEBp NV;RbFZj\GWuYYnzJGcxN0dzIHPlcIwh[3mlbHWgdJJw\3Knc4Ppc44> NWDweoZoOTd4M{G2OFY>
CNE-2 MVnGeY5kfGmxbjDBd5NigQ>? NYHV[GJXPiEQvF2= MmHCNlQhcA>? MlvR[IVt[Xm|IFewM2cyKGOnbHygZ5lkdGVicILv[5Jme3Orb36= MnK1NVc3OzF4NE[=
C666-1 M4PXbGZ2dmO2aX;uJGF{e2G7 NE\JNFg3KM7:TR?= MVqyOEBp MUHk[YxigXNiR{CvS|Eh[2WubDDjfYNt\SCycn;ndoV{e2mxbh?= NXLXenE4OTd4M{G2OFY>

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

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Clinical Trial Information

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

Tech Support

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

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID