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  M1LMT2Z2dmO2aX;uJGF{e2G7 M1HDelUxOOLCiX7NxsA> NX;ldopzOTZiaB?= M1PrWIlv[3KnYYPld{BEYEOUNDDlfJBz\XO|aX;uJJNq\26rZnnjZY51dHl? M2XrZVI2Pjd4Nkmx
SN186 M{XiXmZ2dmO2aX;uJGF{e2G7 NYXVdml[PTBy4pEJcm3DqA>? NFTSdXAyPiCq NH\QXXRqdmO{ZXHz[ZMhS1iFUkSg[ZhxemW|c3nvckB{cWewaX\pZ4FvfGy7 Mnu4NlU3PzZ4OUG=
SN179  M{jCdWZ2dmO2aX;uJGF{e2G7 NHm0PVY2ODEkgJnuUeKh NVXpWZNsOTZiaB?= Mlj4[Y5p[W6lZYOgeIhmKEO[Q1yxNkBlcXKnY4Tl[EBucWe{YYTpc44> NHWzdJIzPTZ5Nk[5NS=>
SN179  MX3GeY5kfGmxbjDBd5NigQ>? MUi1NFDjiImwTdMg NI\kdFgyPiCq M3z1W4lv[3KnYYPld{Bj[XOjbDDtbYdz[XSrb39CpC=> NUW0[XlFOjV4N{[2PVE>
Jurkat NGT1TW1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUfLdI9vPzMEoHlCpC=> NVGyOZlyT0l3ME2xMlUhyrFiMD6yJO69VQ>? NGD5XmwzPDZ6MUKwOS=>
K-562 MlH2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFHkZZA4OsLiaNMg NFzrfFZIUTVyPUGuPEDDuSByLkGg{txO NGTBU5ozPDZ6MUKwOS=>
NCTC-2544 NFzRUZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkLIO|LDqGkEoB?= NXv1SZNtT0l3ME20MlYhyrFiMD6zJO69VQ>? NYXyZ4RjOjR4OEGyNFU>
A-431 M1nke2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUC3NuKhcMLi NG\DdotIUTVyPUKuOEDDuSByLkOg{txO MnvaNlQ3QDF{MEW=
SK-N-SH NULzbWdtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoHvNE43OjVvMkCg{txO M3LYXVQ5KGh? Mlv2SG1UVw>? MWDpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M{TNdFI1Ozl7MEe0
SH-SY5Y MoTKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmWyNE43OjVvMkCg{txO NIe4cnY1QCCq NGHZeFJFVVOR M1;N[4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M{O3OFI1Ozl7MEe0
SK-N-SH NWHQNI5tSXCxcITvd4l{cSCDc4PhfS=> MXy1M|ExNzJyIN88US=> MYC0PEBp MULEUXNQ NFzUN5BqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 MoX1NlQ{QTlyN{S=
SH-SY5Y MoPNRZBweHSxc3nzbUBCe3OjeR?= NF[xU3I2NzFyL{KwJO69VQ>? Mo\sOFghcA>? M4P4cmROW09? NVzPV5R6cW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> NYCzTo84OjR|OUmwO|Q>
SK-N-SH MoDYSpVv[3Srb36gRZN{[Xl? NEXBS3o2NzFyL{KwJO69VQ>? M1j6WlQ5KGh? MX;EUXNQ NHvUZWhqdmS3Y3XzJGcyKHCqYYPlJINmdGxiY4njcIUh[XK{ZYP0 NIfiXYwzPDN7OUC3OC=>
SH-SY5Y Mm\1SpVv[3Srb36gRZN{[Xl? MlnLOU8yOC9{MDFOwG0> M3X6NVQ5KGh? MUTEUXNQ NUXjV5lXcW6mdXPld{BIOSCyaHHz[UBk\WyuIHP5Z4xmKGG{cnXzeC=> NWrBOYl5OjR|OUmwO|Q>
SK-N-SH NYPNTWdtTnWwY4Tpc44hSXO|YYm= MnLWNU82NzFyIN88US=> Ml\hOFghcA>? NFyy[5JFVVOR NVjQeHZpcW6qaXLpeJMhWkWWIIDoc5NxcG:{eXzheIlwdg>? NXX6c2xuOjR|OUmwO|Q>
SH-SY5Y NYi4WGZXTnWwY4Tpc44hSXO|YYm= M2q1V|EwPS9zMDFOwG0> MljCOFghcA>? NIPpb5NFVVOR NHzFUXNqdmirYnn0d{BTTVRicHjvd5Bpd3K7bHH0bY9v MkP0NlQ{QTlyN{S=
SK-N-SH Mm\ySpVv[3Srb36gRZN{[Xl? NWLo[5JKPS9zMDFOwG0> MXu0PEBp Mk\2SG1UVw>? Moi2bY5pcWKrdIOgbJVu[W5iTlKgZ4VtdCCvaXfyZZRqd25? NF;G[YgzPDN7OUC3OC=>
SH-SY5Y NEX2S|VHfW6ldHnvckBCe3OjeR?= Mlv2OU8yOCEQvF2= MnXOOFghcA>? NWC3dYE4TE2VTx?= M1HLcYlvcGmkaYTzJIh2dWGwIF7CJINmdGxibXnndoF1cW:w MVGyOFM6QTB5NB?=
SK-N-SH Mo\jSpVv[3Srb36gRZN{[Xl? NHTtcWs2NzFyIN88US=> NFrPTHc1QCCq NViwVIZrTE2VTx?= M{\sXIlvcGmkaYTzJIh2dWGwIF7CJINmdGxiaX72ZZNqd25? NHr2NmQzPDN7OUC3OC=>
SH-SY5Y M2nZdmZ2dmO2aX;uJGF{e2G7 MVO1M|ExKM7:TR?= Ml\qOFghcA>? MWrEUXNQ NInT[nhqdmirYnn0d{BpfW2jbjDORkBk\WyuIHnueoF{cW:w NH3qRW8zPDN7OUC3OC=>
SK-N-SH NXfpTHNETnWwY4Tpc44hSXO|YYm= Mn23OUDPxE1? M33UPFI1NzR6L{eyJIg> MXXEUXNQ NYS0co1[e3WycILld5NmeyC2aHWg[ZhxemW|c3nvckBw\iCFWFPSOEBidmRiTV3QNVQhdVKQQR?= NVTUXYw6OjR|OUmwO|Q>
SH-SY5Y MmXJSpVv[3Srb36gRZN{[Xl? M3zxPVUh|ryP MV2yOE81QC95MjDo NV[5WIhGTE2VTx?= M17I[JN2eHC{ZYPz[ZMhfGinIHX4dJJme3Orb36gc4YhS1iFUkSgZY5lKE2PUEG0JI1TVkF? M2OxbFI1Ozl7MEe0
SK-N-SH MV7GeY5kfGmxbjDBd5NigQ>? NXXkXVNKPSEQvF2= NVzzd4p[PDhxN{KgbC=> M3vybmROW09? NEDkV3J{fXCycnXzd4V{KGW6cILld5Nqd25ib3[geIhmKEO[Q2K0JIFv\CCPTWCxOEBxem:2ZXnu MUGyOFM6QTB5NB?=
SH-SY5Y M4XCemZ2dmO2aX;uJGF{e2G7 NHvOVYU2KM7:TR?= M162XVQ5Nzd{IHi= NGnDWHBFVVOR NFi4XG5{fXCycnXzd4V{KGW6cILld5Nqd25ib3[geIhmKEO[Q2K0JIFv\CCPTWCxOEBxem:2ZXnu M{nrdVI1Ozl7MEe0
HMEpC NHXBb4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX\6VI83OSCwTT2xNFAh|ryP MVq0POKhcMLi M3rLR2ROW09? NWHsOmxwcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NV\HOFdbOjRzM{i4OFM>
MCF-7 Ml\GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGTRdYgyKG6PLUGwNEDPxE1? NXHQb4pHPDkEoHlCpC=> MoW0SG1UVw>? NFvZVGZqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NUHWZ3VMOjRzM{i4OFM>
ZR-75-1 MmXKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV[xe2hEOSCwTT2xNFAh|ryP NV[0U3JYPDkEoHlCpC=> MYTEUXNQ NH\xfFFqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? Mk\sNlQyOzh6NEO=
MDA-MB-231 M2W3TWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mlr4NUBvVS1zMECg{txO MWq0POKhcMLi NILvV5lFVVOR M4LzbIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz Mn3wNlQyOzh6NEO=
MDA-MB-468 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfKZoJvOSCwTT2xNFAh|ryP NXfB[3ZyPDkEoHlCpC=> NUXmfoV4TE2VTx?= M1X0dIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MXWyOFE{QDh2Mx?=
T-47-D M2TyVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3THXFEhdk1vMUCwJO69VQ>? M2PkdlQ5yqCqwrC= M2n6cmROW09? NUiyZ|NZcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M17WUVI1OTN6OESz
U251  M{P0SWZ2dmO2aX;uJGF{e2G7 NVzRWpZKOi92L{lihKnPxOLGs9Mg MoK4Ok8yOi9{NDDo NYrQem1KTE2VTx?= M3n0PIlv[3KnYYPld{B1cGViTFOzMWlKKGyndnXsJIlvKGFidHnt[U1l\XCnbnTlcpQh[W6mIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> NFLzcoozOzd7OUi1Ni=>
U87MG NV7Hb4tZTnWwY4Tpc44hSXO|YYm= MlLwNk81NzkkgJpOwQKFu8Li MnvQOk8yOi9{NDDo M{LWbWROW09? MUnpcoNz\WG|ZYOgeIhmKEyFMz3JTUBt\X[nbDDpckBiKHSrbXWt[IVx\W6mZX70JIFv\CCmb4PlMYRmeGWwZHXueEBu[W6wZYK= M4\rPFI{Pzl7OEWy
U251  M{f0OmZ2dmO2aX;uJGF{e2G7 NETZeGM16oDLzs|iiNPDqA>? MonVNk83NzF{IHi= MWTEUXNQ M2juNpN2eHC{ZYPz[ZMh[mG|YXygcIV3\Wy|IH;mJJBpd3OyaH;yfYxifGmxbjDv[kBUPiBqU{KzOU8zOzZrLDC0SU1DWDFiKGSzO{81PiluIHHu[EBCc3RiKGO0O|MqKGmwIHGgeIlu\S2mZYDlcoRmdnRibXHucoVzyqB? M3\OfFI{Pzl7OEWy
U87MG MXHGeY5kfGmxbjDBd5NigQ>? MYG05qCK|r{khMRCpC=> NX3VZWdSOi94L{GyJIg> M1PDcGROW09? NVPaWpdSe3WycILld5NmeyCkYYPhcEBt\X[nbIOgc4YheGixc4Doc5J6dGG2aX;uJI9nKFN4IDjTNlM2NzJ|NjmsJFRGNUKSMTCoWFM4NzR4KTygZY5lKEGtdDCoV|Q4OyliaX6gZUB1cW2nLXTldIVv\GWwdDDtZY5v\XMEoB?= NEjoTJEzOzd7OUi1Ni=>
H1650  NX3YZodLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mm[1TWM2OD1|LkZCtVEvOiEQvF2= MYOyN|I4PDd3OB?=
HUVECs  M2foZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlnKO|IhcA>? NEDOVXdKSzVywrC9JFcvOSEQvH3vcE9N MWOyNlYyOTB{Nx?=
KYN-2  NY\aS4p[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnfEO|IhcA>? NUTyXFM6UUN3MNMgQUA5NjFizsztc4wwVA>? MU[yNlYyOTB{Nx?=
HuH-7  M3PNUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnzYO|IhcA>? MWrJR|UxyqB;IEmuOEDPxG2xbD;M NWfhRm9ZOjJ4MUGwNlc>
HUVECs  NIG3TZpHfW6ldHnvckBCe3OjeR?= NVfPToRkOS93L{GwJO69VQ>? NIXJW4syKGh? NFyxSG9{cWewaX\pZ4FvfGy7IHnubIljcXS|IG\FS2ZTNTJicHjvd5Bpd3K7bHH0bY9v NGTQZYEzOjZzMUCyOy=>
HAK1-B MYnGeY5kfGmxbjDBd5NigQ>? M2fYWFEwPS9zMDFOwG0> NV3zR|dLOSCq NVvDXWI5e3WycILld5NmeyCHR1\SJJBpd3OyaH;yfYxifGmxbh?= M{fVbVIzPjFzMEK3
UM-22A NX;nNpVQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWCwMVYh|ryP M1jvT|czKGh? M17XZmROW09? NV3LS|ZucW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M3f5PFIzOzB5N{O1
UM-22B NHjwVotIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFrWOI0xNTZizszN M4\1cFczKGh? MX\EUXNQ NE[1eGlqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M{HwcFIzOzB5N{O1
PCI-37A Mlq2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NELpNlQxNTZizszN Mo\RO|IhcA>? MYnEUXNQ M{XEcolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MVyyNlMxPzd|NR?=
PCI-37B MkTxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFXIOlYxNTZizszN M1KydVczKGh? NULOTo9lTE2VTx?= M1nObYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NXjOXWZPOjJ|MEe3N|U>
PCI-15B NXznVnhNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2\r[lAuPiEQvF2= NWXmdnV4PzJiaB?= MVTEUXNQ NV7nbGNpcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MlKyNlI{ODd5M{W=
SCC-25 NX60R4M2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWK5O2R4OC14IN88US=> NFH0TWw4OiCq NIDGSo5FVVOR NWPHcY9kcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M{C1U|IzOzB5N{O1
UM-22A NXvQbnVETnWwY4Tpc44hSXO|YYm= MXiwMVExKM7:TR?= NYX4cZhUOjRiaB?= M{LvZmROW09? MlnvbY5pcWKrdIOgeIhmKGGldHn2ZZRqd25ib3[geIhmKEWJRmKgeJlzd3OrbnWgb4lv[XOnIHHu[EBidHOxIHTlZ5Jm[XOnczD0bIUh\XiycnXzd4lwdiCxZjDwbI9{eGixconsZZRm\CCob4Ltd{Bw\iC2aHWg[I94dnO2cnXhcUB{cWewYXzpcoch\WynbXXueJMtKFOWQWSzJIFv\CCPQWDL M{DjclIzOzB5N{O1
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201T  NVTEZpdSTnWwY4Tpc44hSXO|YYm= M2\adVEwPS9zMDFOwG0> NID0bos1QCCq NGmyXIVFVVOR MXjicI9kc3NidHjlJJBpd3OyaH;yfYxifGmxbjDv[kBCc3RiaX7keYNm\CCkeTDWSWdHSw>? MWGyNlI2QDR5Nh?=
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HTB3 Mo[1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYXMc2NnOC1{MDFOwG0> MnPENlTDqGh? NHfuTZFqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NGPDbpAyQTJ{MEK1Oi=>
HT1376 NUfjWZJMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYmwMVIxKM7:TR?= MYmyOOKhcA>? NWHhVlJkcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NVmzd|NCOTl{MkCyOVY>
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CRL1749 NILMbGxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{n2XVAuOjBizszN M{jmRVI1yqCq MnLQbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NX3aPWRROTl{MkCyOVY>
T24 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWjCNFhQOC1{MDFOwG0> NWn4U4szOjUEoHi= NV\ocmxGcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M130XlE6OjJyMkW2
SUP MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUL6fIRUOC1{MDFOwG0> MlTkNlTDqGh? M{T6PIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M4fjcFE6OjJyMkW2
HTB9 MlP3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4HQTlAuOjBizszN MlnqNlTDqGh? NV;uZ2RMcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MVqxPVIzODJ3Nh?=
ACC3 Mn\mS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVLxPZlJOC1zMDFOwG0> MmrVO|IhcA>? Mn3FbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> Mo\MNVg3QThyMkW=
ACC2 NG[4O5pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml\ENE0yOCEQvF2= NVLKdXZ[PzJiaB?= MlzCbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NX;CW4psOTh4OUiwNlU>
ACCM MmjQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIXvWooxNTFyIN88US=> NULuTZFtPzJiaB?= NILrO2VqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MVqxPFY6QDB{NR?=
ACC3 M1TYZmFxd3C2b4Ppd4khSXO|YYm= MWqwMVExKM7:TR?= NUPBOWw4PzJiaB?= NV7zV2hzcW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> NX34ZpkzOTh4OUiwNlU>
ACC2 NH;mRlZCeG:ydH;zbZNqKEG|c3H5 M{\2OFAuOTBizszN MXq3NkBp MmDFbY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= MYixPFY6QDB{NR?=
ACCM MlfJRZBweHSxc3nzbUBCe3OjeR?= NVzBU3ZTOC1zMDFOwG0> NGLod2s4OiCq MU\pcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 NFv5UlUyQDZ7OECyOS=>
EHMES-1 MljtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mm\QO|IhcA>? MU\EUXNQ MojrTWM2OD1zMD62JO69VQ>? Mo\LNVg{PjR{NEi=
EHMES-10 NFW0flhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnMTlg4OiCq MYPEUXNQ NVSzSVB2UUN3ME2wMlMh|ryP NV7nXZB5OTh|NkSyOFg>
211H NIezVmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUm3NkBp Mn;5SG1UVw>? MXjJR|UxRTJwMjFOwG0> MnjNNVg{PjR{NEi=
H28 MlHnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2HCNVczKGh? MnTmSG1UVw>? NHWwe5FKSzVyPUGuPEDPxE1? NHjld|kyQDN4NEK0PC=>
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H2452 Ml70S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml3KO|IhcA>? MVLEUXNQ M4H0ZWlEPTB;NT61JO69VQ>? NWLDWHNZOTh|NkSyOFg>
CNE-1 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFLxPYwxNjFvMkWuOkDPxE1? NX7nNoViPDhiaB?= NEHMUIdKSzVyPUOuOkDPxE1? M1LJd|E4PjNzNkS2
CNE-2 M2nCNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUDtbGxYOC5zLUK1MlYh|ryP NHj3NZI1QCCq NWrTbppJUUN3ME22MlIh|ryP MWmxO|Y{OTZ2Nh?=
C666-1 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHL5WlExNjFvMkWuOkDPxE1? MWO0PEBp NEL1UHpKSzVyPUKzMlQh|ryP NFXD[WEyPzZ|MU[0Oi=>
CNE-1 NYfpcFdTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV6wMlEuOjVwNjFOwG0> NXjuOHRrPzJiaB?= MmPxTWM2OD1{LkOg{txO M{PoVVE4PjNzNkS2
CNE-2 M2DM[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXKwMlEuOjVwNjFOwG0> NXnEeoRkPzJiaB?= NVT1TlZzUUN3ME2zMlYh|ryP M2fLe|E4PjNzNkS2
C666-1 MkjaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkfuNE4yNTJ3Lk[g{txO M{PZOFczKGh? M3LYSWlEPTB;ND64OkDPxE1? Ml24NVc3OzF4NE[=
CNE-1 M3XYXmZ2dmO2aX;uJGF{e2G7 NIflV4w3KM7:TR?= NU\hO|NMOjRiaB?= M1fwNIRmdGG7czDHNE9IOSClZXzsJIN6[2ynIIDyc4dz\XO|aX;u MXqxO|Y{OTZ2Nh?=
CNE-2 M2LITmZ2dmO2aX;uJGF{e2G7 Mk\oOkDPxE1? MVuyOEBp NXnHSGZ1\GWuYYnzJGcxN0dzIHPlcIwh[3mlbHWgdJJw\3Knc4Ppc44> NIHHOW0yPzZ|MU[0Oi=>
C666-1 MYHGeY5kfGmxbjDBd5NigQ>? NWT5SIpjPiEQvF2= NHnu[3QzPCCq MYfk[YxigXNiR{CvS|Eh[2WubDDjfYNt\SCycn;ndoV{e2mxbh?= MUixO|Y{OTZ2Nh?=

... 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).

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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.

Handling Instructions

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

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID