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Vandetanib VEGFR inhibitor

Name: Vandetanib
Brand: Selleck Chemicals
SKU: S1046
Rating: 5 (114 reviews)

Cat.No.S1046

Vandetanib 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. This compound increases apoptosis and induces autophagy by increasing the level of reactive oxygen species (ROS).

Chemical Structure

Molecular Weight: 475.35

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Quality Control

Batch: Purity: 99.99%

99.99

Related Targets	EGFR PDGFR FGFR c-Met Src MEK CSF-1R FLT3 HER2 c-Kit
Other VEGFR Inhibitors	SAR131675 SU 5402 Cediranib (AZD2171) Vatalanib (PTK787) 2HCl Anlotinib (AL3818) Dihydrochloride Linifanib (ABT-869) Apatinib (YN968D1) Apatinib (YN968D1) mesylate Ki8751 ZM 323881 HCl

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
SN179	Function Assay	500 nM	16 h		increases CXCR4 expression significantly	25676691
SN186	Function Assay	500 nM	16 h		increases CXCR4 expression significantly	25676691
SN179	Function Assay	500 nM	16 h		enhances the CXCL12 directed migration	25676691
SN179	Function Assay	500 nM	16 h		increases basal migration	25676691
Jurkat	Growth Inhibition Assay		72 h		GI50=1.5 ± 0.2 μM	24681205
K-562	Growth Inhibition Assay		72 h		GI50=1.8 ± 0.1 μM	24681205
NCTC-2544	Growth Inhibition Assay		72 h		GI50=4.6 ± 0.3 μM	24681205
A-431	Growth Inhibition Assay		72 h		GI50=2.4 ± 0.3 μM	24681205
SK-N-SH	Growth Inhibition Assay	0.625-20 μM	48 h	DMSO	inhibits cell growth in a dose dependent manner	24399074
SH-SY5Y	Growth Inhibition Assay	0.625-20 μM	48 h	DMSO	inhibits cell growth in a dose dependent manner	24399074
SK-N-SH	Apoptosisi Assay	5/10/20 μM	48 h	DMSO	induces apoptosis dose dependently	24399074
SH-SY5Y	Apoptosisi Assay	5/10/20 μM	48 h	DMSO	induces apoptosis dose dependently	24399074
SK-N-SH	Function Assay	5/10/20 μM	48 h	DMSO	induces G1 phase cell cycle arrest	24399074
SH-SY5Y	Function Assay	5/10/20 μM	48 h	DMSO	induces G1 phase cell cycle arrest	24399074
SK-N-SH	Function Assay	1/5/10 μM	48 h	DMSO	inhibits RET phosphorylation	24399074
SH-SY5Y	Function Assay	1/5/10 μM	48 h	DMSO	inhibits RET phosphorylation	24399074
SK-N-SH	Function Assay	5/10 μM	48 h	DMSO	inhibits human NB cell migration	24399074
SH-SY5Y	Function Assay	5/10 μM	48 h	DMSO	inhibits human NB cell migration	24399074
SK-N-SH	Function Assay	5/10 μM	48 h	DMSO	inhibits human NB cell invasion	24399074
SH-SY5Y	Function Assay	5/10 μM	48 h	DMSO	inhibits human NB cell invasion	24399074
SK-N-SH	Function Assay	5 μM	24/48/72 h	DMSO	suppresses the expression of CXCR4 and MMP14 mRNA	24399074
SH-SY5Y	Function Assay	5 μM	24/48/72 h	DMSO	suppresses the expression of CXCR4 and MMP14 mRNA	24399074
SK-N-SH	Function Assay	5 μM	48/72 h	DMSO	suppresses expression of the CXCR4 and MMP14 protein	24399074
SH-SY5Y	Function Assay	5 μM	48/72 h	DMSO	suppresses expression of the CXCR4 and MMP14 protein	24399074
HMEpC	Growth Inhibition Assay	1 nM-100 μM	48 h	DMSO	inhibits cell growth in a dose dependent manner	24138843
MCF-7	Growth Inhibition Assay	1 nM-100 μM	48 h	DMSO	inhibits cell growth in a dose dependent manner	24138843
ZR-75-1	Growth Inhibition Assay	1 nM-100 μM	48 h	DMSO	inhibits cell growth in a dose dependent manner	24138843
MDA-MB-231	Growth Inhibition Assay	1 nM-100 μM	48 h	DMSO	inhibits cell growth in a dose dependent manner	24138843
MDA-MB-468	Growth Inhibition Assay	1 nM-100 μM	48 h	DMSO	inhibits cell growth in a dose dependent manner	24138843
T-47-D	Growth Inhibition Assay	1 nM-100 μM	48 h	DMSO	inhibits cell growth in a dose dependent manner	24138843
U251	Function Assay	2/4/8 μℳ	6/12/24 h	DMSO	increases the LC3-II level in a time-dependent and dose-dependent manner	23799852
U87MG	Function Assay	2/4/8 μℳ	6/12/24 h	DMSO	increases the LC3-II level in a time-dependent and dose-dependent manner	23799852
U251	Function Assay	4 μℳ	2/6/12 h	DMSO	suppresses basal levels of phosphorylation of S6 (S235/236), 4E-BP1 (T37/46), and Akt (S473) in a time-dependent manner	23799852
U87MG	Function Assay	4 μℳ	2/6/12 h	DMSO	suppresses basal levels of phosphorylation of S6 (S235/236), 4E-BP1 (T37/46), and Akt (S473) in a time-dependent manner	23799852
H1650	Growth Inhibition Assay				IC50=3.5±1.2 μM	23274758
HUVECs	Growth Inhibition Assay		72 h		IC50 = 7.1 μmol/L	22611027
KYN-2	Growth Inhibition Assay		72 h		IC50 = 8.1 μmol/L	22611027
HuH-7	Growth Inhibition Assay		72 h		IC50 = 9.4 μmol/L	22611027
HUVECs	Function Assay	1/5/10 μM	1 h		significantly inhibits VEGFR-2 phosphorylation	22611027
HAK1-B	Function Assay	1/5/10 μM	1 h		suppresses EGFR phosphorylation	22611027
UM-22A	Growth Inhibition Assay	0-6 μM	72 h	DMSO	inhibits cell growth in a dose dependent manner	22307735
UM-22B	Growth Inhibition Assay	0-6 μM	72 h	DMSO	inhibits cell growth in a dose dependent manner	22307735
PCI-37A	Growth Inhibition Assay	0-6 μM	72 h	DMSO	inhibits cell growth in a dose dependent manner	22307735
PCI-37B	Growth Inhibition Assay	0-6 μM	72 h	DMSO	inhibits cell growth in a dose dependent manner	22307735
PCI-15B	Growth Inhibition Assay	0-6 μM	72 h	DMSO	inhibits cell growth in a dose dependent manner	22307735
SCC-25	Growth Inhibition Assay	0-6 μM	72 h	DMSO	inhibits cell growth in a dose dependent manner	22307735
UM-22A	Function Assay	0-10 μM	24 h	DMSO	inhibits the activation of the EGFR tyrosine kinase and also decreases the expression of phosphorylated forms of the downstream signaling elements, STAT3 and MAPK	22307735
UM-22B	Function Assay	0-10 μM	24 h	DMSO	inhibits the activation of the EGFR tyrosine kinase and also decreases the expression of phosphorylated forms of the downstream signaling elements, STAT3 and MAPK	22307735
PCI-15B	Function Assay	0-10 μM	24 h	DMSO	inhibits the activation of the EGFR tyrosine kinase and also decreases the expression of phosphorylated forms of the downstream signaling elements, STAT3 and MAPK	22307735
PCI-37A	Function Assay	1 μM	24 h	DMSO	downregulates VEGF production	22307735
UM-22A	Function Assay	1 μM	24 h	DMSO	downregulates VEGF production	22307735
PCI-15B	Function Assay	1 μM	24 h	DMSO	downregulates VEGF production	22307735
PCI-15B	Invasion Assay		24 h	DMSO	EC50=558 nM	22307735
PCI-37A	Invasion Assay		24 h	DMSO	EC50=1695 nM	22307735
UM-22A	Invasion Assay		24 h	DMSO	EC50=0.3 nM	22307735
SCC-25	Invasion Assay		24 h	DMSO	EC50=10 nM	22307735
UM-22B	Invasion Assay		24 h	DMSO	EC50=2424 nM	22307735
PCI-37B	Invasion Assay		24 h	DMSO	EC50=1726 nM	22307735
201T	Function Assay	2.5 μM	48 h	DMSO	inhibits phospho-MAPK following EGF	22258476
273T	Function Assay	2.5 μM	48 h	DMSO	inhibits phospho-MAPK following EGF	22258476
A549	Function Assay	2.5 μM	48 h	DMSO	inhibits phospho-MAPK following EGF	22258476
201T	Function Assay	1/5/10 μM	48 h	DMSO	blocks the phosphorylation of Akt induced by VEGFC	22258476
H2052	Growth Inhibition Assay				IC50=1.07±0.04 μM	21970874
H2452	Growth Inhibition Assay				IC50=3.52±1.13 μM	21970874
H28	Growth Inhibition Assay				IC50=0.32±0.07 μM	21970874
MSTO-211H	Growth Inhibition Assay				IC50=1.42±0.03 μM	21970874
Hth83	Growth Inhibition Assay		72 h	DMSO	IC50=3.30 ± 0.66 μM	21220477
C643	Growth Inhibition Assay		72 h	DMSO	IC50=3.65 ± 1.22 μM	21220477
8505C	Growth Inhibition Assay		72 h	DMSO	IC50=7.56 ± 1.13 μM	21220477
Hth74	Growth Inhibition Assay		72 h	DMSO	IC50=8.56 ± 1.01 μM	21220477
SW1736	Growth Inhibition Assay		72 h	DMSO	IC50=9.05 ± 0.55 μM	21220477
Hth7	Growth Inhibition Assay		72 h	DMSO	IC50=9.66 ± 0.38 μM	21220477
Hth104	Growth Inhibition Assay		72 h	DMSO	IC50=±16.98 ± NA μM	21220477
HTB3	Growth Inhibition Assay	0-20 μM	24 h		inhibits cell growth in a dose dependent manner	19220256
HT1376	Growth Inhibition Assay	0-20 μM	24 h		inhibits cell growth in a dose dependent manner	19220256
RT4	Growth Inhibition Assay	0-20 μM	24 h		inhibits cell growth in a dose dependent manner	19220256
J82	Growth Inhibition Assay	0-20 μM	24 h		inhibits cell growth in a dose dependent manner	19220256
CRL1749	Growth Inhibition Assay	0-20 μM	24 h		inhibits cell growth in a dose dependent manner	19220256
T24	Growth Inhibition Assay	0-20 μM	24 h		inhibits cell growth in a dose dependent manner	19220256
SUP	Growth Inhibition Assay	0-20 μM	24 h		inhibits cell growth in a dose dependent manner	19220256
HTB9	Growth Inhibition Assay	0-20 μM	24 h		inhibits cell growth in a dose dependent manner	19220256
ACC3	Growth Inhibition Assay	0-10 μM	72 h		inhibits cell growth in a dose dependent manner	18698025
ACC2	Growth Inhibition Assay	0-10 μM	72 h		inhibits cell growth in a dose dependent manner	18698025
ACCM	Growth Inhibition Assay	0-10 μM	72 h		inhibits cell growth in a dose dependent manner	18698025
ACC3	Apoptosisi Assay	0-10 μM	72 h		induces apoptosis dose dependently	18698025
ACC2	Apoptosisi Assay	0-10 μM	72 h		induces apoptosis dose dependently	18698025
ACCM	Apoptosisi Assay	0-10 μM	72 h		induces apoptosis dose dependently	18698025
EHMES-1	Growth Inhibition Assay		72 h	DMSO	IC50=10.6 μM	18364248
EHMES-10	Growth Inhibition Assay		72 h	DMSO	IC50=0.3 μM	18364248
211H	Growth Inhibition Assay		72 h	DMSO	IC50=2.2 μM	18364248
H28	Growth Inhibition Assay		72 h	DMSO	IC50=1.8 μM	18364248
H2052	Growth Inhibition Assay		72 h	DMSO	IC50=8.0 μM	18364248
H2452	Growth Inhibition Assay		72 h	DMSO	IC50=5.5 μM	18364248
CNE-1	Growth Inhibition Assay	0.1-25.6 μM	48 h		IC50=3.6 μM	17631646
CNE-2	Growth Inhibition Assay	0.1-25.6 μM	48 h		IC50=6.2 μM	17631646
C666-1	Growth Inhibition Assay	0.1-25.6 μM	48 h		IC50=23.4 μM	17631646
CNE-1	Growth Inhibition Assay	0.1-25.6 μM	72 h		IC50=2.3 μM	17631646
CNE-2	Growth Inhibition Assay	0.1-25.6 μM	72 h		IC50=3.6 μM	17631646
C666-1	Growth Inhibition Assay	0.1-25.6 μM	72 h		IC50=4.86 μM	17631646
CNE-1	Function Assay	6 μM	24 h		delays G0/G1 cell cycle progression	17631646
CNE-2	Function Assay	6 μM	24 h		delays G0/G1 cell cycle progression	17631646
C666-1	Function Assay	6 μM	24 h		delays G0/G1 cell cycle progression	17631646
KDR15	Function assay				Inhibitory activity against VEGF stimulated autophosphorylation of VEGFR2 expressed in KDR15 cells, IC50 = 0.015 μM.	16302797
Sf9	Function assay				Inhibition of human recombinant histidine-tagged RET (700-1020) expressed in Sf9 cells by ELISA, IC50 = 0.097 μM.	20409618
TPC1	Antiproliferative assay		72 hrs		Antiproliferative activity against human TPC1 cells expressing RET/PCT1 after 72 hrs by [3H]thymidine incorporation assay, IC50 = 0.116 μM.	20409618
HEK293	Function assay				Inhibition of FGFR1/VEGFR2 chimeric construct expressed in HEK293 cells by ELISA, ED50 = 0.15 μM.	19101155
Sf21	Function assay		15 mins		Inhibition of recombinant His-tagged human KDR expressed in insect Sf21 cells preincubated for 15 mins followed by substrate addition measured after 20 mins by HTRF assay, IC50 = 0.175 μM.	26874741
umbilical vein endothelial cells	Function assay				Inhibition of VEGF-induced proliferation of human umbilical vein endothelial cells, IC50 = 0.4 μM.	15743202
BA/F3	Function assay		48 hrs		Inhibition of KIF5B/RET (unknown origin) expressed in mouse BA/F3 cells assessed as reduction in cell viability after 48 hrs by Cell titre glo-based luminescence assay, IC50 = 0.4 μM.	26874741
BA/F3	Function assay		48 hrs		Inhibition of KDR (unknown origin) expressed in mouse BA/F3 cells assessed as reduction in cell viability after 48 hrs by Cell titre glo-based luminescence assay, IC50 = 0.63 μM.	26874741
umbilical vein endothelial cells	Function assay				Inhibition of basic FGF-induced proliferation of human umbilical vein endothelial cells, IC50 = 1.2 μM.	15743202
HL60	Antiproliferative assay		72 hrs		Antiproliferative activity against human HL60 cells after 72 hrs by MTT assay, IC50 = 1.492 μM.	26995527
293	Function assay				Inhibitory activity against VEGFR2 transiently transfected in 293 adenovirus transfected kidney cells by ELISA, IC50 = 1.66 μM.	16275072
293	Function assay				Inhibition of VEGFR2 in 293 adenovirus transfected kidney cells by cell-based ELISA assay, IC50 = 1.66 μM.	16321531
HEK293	Function assay				Inhibition of VEGFR2 phosphorylation in HEK293 cells by cell-based ELISA, IC50 = 1.66 μM.	16460936
HT-29	Antiproliferative assay		72 hrs		Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 1.925 μM.	26995527
DU145	Antiproliferative assay		72 hrs		Antiproliferative activity against human DU145 cells after 72 hrs by MTT assay, IC50 = 1.974 μM.	26995527
MGHU3	Antiproliferative assay		72 hrs		Antiproliferative activity against human MGHU3 cells after 72 hrs by CellTiter-Glo assay, IC50 = 2.5 μM.	30309671
A549	Antiproliferative assay		72 hrs		Antiproliferative activity against human A549 cells after 72 hrs by CellTiter-Glo assay, IC50 = 2.5 μM.	30309671
RT112	Antiproliferative assay		72 hrs		Antiproliferative activity against human RT112 cells after 72 hrs by CellTiter-Glo assay, IC50 = 2.5 μM.	30309671
A549	Antiproliferative assay		72 hrs		Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, IC50 = 2.63 μM.	26995527
CHO	Function assay				Inhibition of VEGFR induced autophosphorylation of human Vascular endothelial growth factor receptor 2 (VEGFR2) transfected in CHO cells, IC50 = 2.673 μM.	12477352
MCF7	Antiproliferative assay		72 hrs		Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay, IC50 = 3.536 μM.	26995527
PANC1	Antiproliferative assay		72 hrs		Antiproliferative activity against human PANC1 cells after 72 hrs by MTT assay, IC50 = 4.107 μM.	26995527
HT-29	Antiproliferative assay	10 uM	72 hrs		Antiproliferative activity against human HT-29 cells at 10 uM after 72 hrs by MTS assay, IC50 = 4.2 μM.	21353546
EAhy926	Antiproliferative assay	10 uM	72 hrs		Antiproliferative activity against human EAhy926 cells at 10 uM after 72 hrs by MTS assay, IC50 = 5.1 μM.	21353546
MCF7	Antiproliferative assay		48 hrs		Antiproliferative activity against human MCF7 cells measured after 48 hrs by MTT assay, IC50 = 11.83 μM.	27688180
MCF7	Cytotoxicity assay		48 hrs		Cytotoxicity in human MCF7 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay, IC50 = 16.52 μM.	28942113
MCF7	Antiproliferative assay		48 hrs		Antiproliferative activity against human MCF7 cells after 48 hrs by MTT assay, IC50 = 18.5 μM.	26741358
MCF7	Antiproliferative assay		48 hrs		Antiproliferative activity against human MCF7 cells after 48 hrs by MTT assay, IC50 = 18.5 μM.	26475519
HT-29	Antiproliferative assay		48 hrs		Antiproliferative activity against human HT-29 cells measured after 48 hrs by MTT assay, IC50 = 18.95 μM.	27688180
H460	Antiproliferative assay		48 hrs		Antiproliferative activity against human H460 cells measured after 48 hrs by MTT assay, IC50 = 37.1 μM.	27688180
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
DAOY	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
BT-37	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
RD	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
SK-N-SH	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
MG 63 (6-TG R)	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
NB1643	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
OHS-50	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
SK-N-SH	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
Rh41	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
Rh41	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
SK-N-MC	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
LAN-5	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
Rh18	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	475.35	Formula	C₂₂H₂₄BrFN₄O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	443913-73-3	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	ZD6474			Smiles	CN1CCC(CC1)COC2=C(C=C3C(=C2)N=CN=C3NC4=C(C=C(C=C4)Br)F)OC

Solubility

In vitro
Batch:

DMSO : 60 mg/mL (126.22 mM) Warmed with 50°C water bath; Ultrasonicated;
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	3.000mg/ml (6.31mM)	Taking the 1 mL working solution as an example, add 50 μL of 60 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Mechanism of Action

Targets/IC₅₀/Ki	VEGFR2 (Cell-free assay) 40 nM VEGFR3 (Cell-free assay) 110 nM EGFR (Cell-free assay) 500 nM
In vitro	Vandetanib also inhibits VEGFR3 and EGFR with IC50 of 110 nM and 500 nM, respectively. This compound 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. It 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. This chemical inhibits tumour cell growth with IC50 of 2.7 μM (A549) to 13.5 μM (Calu-6). It displays an inhibitory effect on the basal ABCG2-ATPase. Parental and ABCG2-expressing A431 cells showed similar sensitivities toward this compound. Exposure to EGFR inhibitors decreases pEGFR levels in A431 cells, with this compound displaying only a moderate effect. It 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. It inhibits both PC3wt and PC3R cell lines with similar IC50 of 13.3 μM and 11.5 μM, respectively. This chemical suppresses phosphorylation of VEGFR2 in HUVEC and EGFR in hepatoma cells and inhibits cell proliferation. It 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. This compound 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. Its 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.
Kinase Assay	Kinase inhibition
Kinase Assay	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 K_m (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.
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. This compound (100 mg/kg) inhibits the tumour-induced blood vessel formation by 79%. It (12.5-100 mg/kg, orally) shows great tumour growth inhibition in human tumour 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. In PC3wt xenografts, administration of this compound alone exerts paradoxical tumour growth stimulating effects. In PC3R xenografts, the low dose of this chemical (25 mg/kg) has no significant effect relative to control, whereas the high dose (50 mg/kg) significantly inhibits tumour growth compared with control. In contrast, the high-dose combination reveals a significant negative interaction between this compound 50 mg/kg and docetaxel 30 mg/kg in PC3R cells. In tumour-bearing mice, it suppresses phosphorylation of VEGFR2 and EGFR in tumour tissues, significantly decreases tumour vessel density, enhances tumour cell apoptosis, suppresses tumour growth, improves survival, reduces number of intrahepatic metastases, and up-regulates VEGF, TGF-alpha and EGF in tumour tissues. Treatment with this compound is not associated with serious adverse events, including ALT abnormality, bone marrow suppression or body weight loss. This chemical treatment of nude mice bearing palpable GEO colon cancer xenografts (which are sensitive to inhibition of EGFR signalling) induces dose-dependent tumour growth inhibition.
References	[1] https://pubmed.ncbi.nlm.nih.gov/12183421/ [2] https://pubmed.ncbi.nlm.nih.gov/22548830/ [3] https://pubmed.ncbi.nlm.nih.gov/22608542/ [4] https://pubmed.ncbi.nlm.nih.gov/22611027/ [5] https://pubmed.ncbi.nlm.nih.gov/12684431/

Applications

Methods	Biomarkers	Images	PMID
Western blot	p-ERK / ERK / p-AKT / AKT p-EGFR / EGFR		19622715
Growth inhibition assay	Cell viability		24261856

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03291379	Completed	Carcinoma Hepatocellular\|Metastatic Colorectal Cancer	Boston Scientific Corporation\|Biocompatibles UK Ltd	May 17 2017	Early Phase 1
NCT02495103	Terminated	Renal Cell Carcinoma\|Hereditary Leiomyomatosis\|Renal Cell Cancer	National Cancer Institute (NCI)\|National Institutes of Health Clinical Center (CC)	August 26 2015	Phase 1\|Phase 2
NCT02530411	Unknown status	Neoplasms	Velindre NHS Trust\|Cancer Research UK\|AstraZeneca	April 2015	Phase 2
NCT02268734	Completed	Metastatic Sporadic Medullary Thyroid Cancer	Fondazione IRCCS Istituto Nazionale dei Tumori Milano	April 2014	--
NCT01876784	Completed	Differentiated Thyroid Cancer	Genzyme a Sanofi Company\|Sanofi	September 17 2013	Phase 3
NCT01661179	Completed	Unresectable Locally Advanced or Metastatic Medullary Thyroid Carcinoma	Genzyme a Sanofi Company\|Sanofi	November 2012	Phase 1\|Phase 2

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