kinase insert domain receptor | Type IV RTKs: VEGF (vascular endothelial growth factor) receptor family | IUPHAR/BPS Guide to PHARMACOLOGY

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kinase insert domain receptor

Target not currently curated in GtoImmuPdb

Target id: 1813

Nomenclature: kinase insert domain receptor

Abbreviated Name: VEGFR-2

Family: Type IV RTKs: VEGF (vascular endothelial growth factor) receptor family

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 1356 4q11-q12 KDR kinase insert domain receptor
Mouse - 1345 5 Kdr kinase insert domain protein receptor
Rat - 1343 14 Kdr kinase insert domain receptor
Previous and Unofficial Names
CD309 | fetal liver kinase 1 | FLK1 | FLK4 | kinase insert domain receptor (a type III receptor tyrosine kinase) | vascular endothelial growth factor receptor 2
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the kinase domain of human vascular endothelial growth factor receptor 2.
PDB Id:  1VR2
Resolution:  2.4Å
Species:  Human
References:  46
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of VEGFR2 (juxtamembrane and kinase domains) in complex with axitinib.
PDB Id:  4AG8
Ligand:  axitinib
Resolution:  2.0Å
Species:  Human
References:  45
Enzyme Reaction
EC Number: 2.7.10.1
Natural/Endogenous Ligands
VEGFA {Sp: Human}
VEGFC {Sp: Human}
VEGFE {Sp: Human}

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
pegdinetanib Hs Inhibition ~9.0 pKd 27
pKd ~9.0 (Kd ~1x10-9 M) [27]
cediranib Hs Inhibition 9.0 pKd 15
pKd 9.0 (Kd 1.1x10-9 M) [15]
SU-14813 Hs Inhibition 8.6 pKd 15
pKd 8.6 (Kd 2.3x10-9 M) [15]
motesanib Hs Inhibition 8.6 pKd 15
pKd 8.6 (Kd 2.6x10-9 M) [15]
BIBF-1202 Hs Inhibition 8.5 pKd 15
pKd 8.5 (Kd 2.9x10-9 M) [15]
axitinib Hs Inhibition 8.2 pKd 15
pKd 8.2 (Kd 5.9x10-9 M) [15]
pazopanib Hs Inhibition 7.8 pKd 15
pKd 7.8 (Kd 1.4x10-8 M) [15]
RG-1530 Hs Inhibition 7.8 pKd 68
pKd 7.8 (Kd 1.5x10-8 M) [68]
sorafenib Hs Inhibition 7.2 pKd 15
pKd 7.2 (Kd 5.9x10-8 M) [15]
vatalanib Hs Inhibition 7.2 pKd 15
pKd 7.2 (Kd 6.2x10-8 M) [15]
PLX-4720 Hs Inhibition 8.1 pKi 47
pKi 8.1 (Ki 9x10-9 M) [47]
TAS-115 Hs Inhibition 7.9 pKi 23
pKi 7.9 (Ki 1.2x10-8 M) [23]
VEGF receptor tyrosine kinase inhibitor II Hs Inhibition 7.8 pKi 16
pKi 7.8 (Ki 1.5x10-8 M) [16]
cabozantinib Hs Inhibition 10.5 pIC50 77
pIC50 10.5 (IC50 3.5x10-11 M) [77]
tivozanib Hs Inhibition 9.8 pIC50 48
pIC50 9.8 (IC50 1.6x10-10 M) [48]
axitinib Hs Inhibition 9.6 pIC50 41
pIC50 9.6 (IC50 2.5x10-10 M) [41]
cediranib Hs Inhibition >9.0 pIC50 73
pIC50 >9.0 (IC50 <1x10-9 M) [73]
VEGF receptor tyrosine kinase inhibitor III Hs Inhibition 9.0 pIC50 19
pIC50 9.0 (IC50 1x10-9 M) [19]
apatinib Hs Inhibition 9.0 pIC50 67
pIC50 9.0 (IC50 1x10-9 M) [67]
Description: Assay used apatinib mesylate (YN968D1)
tesevatinib Hs Inhibition 8.8 pIC50 26
pIC50 8.8 (IC50 1.5x10-9 M) [26]
compound 13a [PMID: 23639540] Hs Inhibition 8.8 pIC50 18
pIC50 8.8 (IC50 1.68x10-9 M) [18]
MLKL compound 1 Hs Inhibition 8.7 pIC50 57
pIC50 8.7 (IC50 2x10-9 M) [57]
ilorasertib Hs Inhibition 8.7 pIC50 28
pIC50 8.7 (IC50 2x10-9 M) [28]
Description: Measuring inhibition of kinase activity in a biochemical assay.
foretinib Hs Inhibition 8.2 – 9.1 pIC50 48
pIC50 8.2 – 9.1 (IC50 6.8x10-9 – 8x10-10 M) [48]
motesanib Hs Inhibition 8.5 pIC50 48
pIC50 8.5 (IC50 3x10-9 M) [48]
compound 8i [PMID: 22765894] Hs Inhibition 8.4 – 8.6 pIC50 37,78
pIC50 8.6 (IC50 2.6x10-9 M) [78]
pIC50 8.4 (IC50 4x10-9 M) [37]
dorsomorphin Hs Inhibition 8.4 pIC50 43
pIC50 8.4 (IC50 4x10-9 M) [43]
Description: Assayed using AMPK heterotrimeric complex containing α2, β1, γ1 subunits
linifanib Hs Inhibition 8.4 pIC50 2
pIC50 8.4 (IC50 4x10-9 M) [2]
lenvatinib Hs Inhibition 8.4 pIC50 48
pIC50 8.4 (IC50 4x10-9 M) [48]
lucitanib Hs Inhibition 8.4 pIC50 80
pIC50 8.4 (IC50 4x10-9 M) [80]
CEP-11981 Hs Inhibition 8.4 pIC50 34
pIC50 8.4 (IC50 4x10-9 M) [34]
compound 8h [PMID: 22765894] Hs Inhibition 8.4 pIC50 37
pIC50 8.4 (IC50 4.2x10-9 M) [37]
famitinib Hs Inhibition 8.3 pIC50 11
pIC50 8.3 (IC50 5x10-9 M) [11]
sitravatinib Hs Inhibition 8.3 pIC50 52
pIC50 8.3 (IC50 5x10-9 M) [52]
Description: In a biochemical enzyme activity assay.
tafetinib Hs Inhibition 8.3 pIC50 72
pIC50 8.3 (IC50 5x10-9 M) [72]
Description: In a radiometric biochemical protein kinase assay.
LY2874455 Hs Inhibition 8.1 pIC50 79
pIC50 8.1 (IC50 7x10-9 M) [79]
Description: In vitro biochemical assay result
CS2164 Hs Inhibition 8.1 pIC50 81
pIC50 8.1 (IC50 7x10-9 M) [81]
Description: Inhibition in a biochemical assay.
OSI-930 Hs Inhibition 8.1 pIC50 25
pIC50 8.1 (IC50 9x10-9 M) [25]
altiratinib Hs Inhibition 8.0 pIC50 21
pIC50 8.0 (IC50 9.2x10-9 M) [21]
vandetanib Hs Inhibition 8.0 pIC50 31
pIC50 8.0 (IC50 9x10-9 M) [31]
glesatinib Hs Inhibition 8.0 pIC50 12
pIC50 8.0 (IC50 1x10-8 M) [12]
CP-547632 Hs Inhibition 8.0 pIC50 7
pIC50 8.0 (IC50 1.1x10-8 M) [7]
Ki-20227 Hs Inhibition 7.9 pIC50 50
pIC50 7.9 (IC50 1.2x10-8 M) [50]
PP121 Hs Inhibition 7.9 pIC50 4
pIC50 7.9 (IC50 1.2x10-8 M) [4]
regorafenib Hs Inhibition 7.9 pIC50 75
pIC50 7.9 (IC50 1.3x10-8 M) [75]
golvatinib Hs Inhibition 7.8 pIC50 49
pIC50 7.8 (IC50 1.6x10-8 M) [49]
Description: Measured as inhibition of VEGFR-2 autophosphorylation in HUVEC cells.
VEGF receptor 2 kinase inhibitor IV Hs Inhibition 7.7 pIC50 22
pIC50 7.7 (IC50 1.9x10-8 M) [22]
vatalanib Hs Inhibition 7.7 pIC50 39
pIC50 7.7 (IC50 2.1x10-8 M) [39]
nintedanib Hs Inhibition 7.7 pIC50 33
pIC50 7.7 (IC50 2.1x10-8 M) [33]
surufatinib Hs Inhibition 7.7 pIC50 59
pIC50 7.7 (IC50 2.1x10-8 M) [59]
Description: In a biochemical assay using recombinant KDR kinase catalytic domain.
sunitinib Hs Inhibition 7.7 pIC50 36
pIC50 7.7 (IC50 2.26x10-8 M) [36]
AZD4547 Hs Inhibition 7.6 pIC50 5
pIC50 7.6 (IC50 2.4x10-8 M) [5]
brivanib Hs Inhibition 7.6 pIC50 8
pIC50 7.6 (IC50 2.5x10-8 M) [8]
SU11652 Hs Inhibition 7.6 pIC50 62
pIC50 7.6 (IC50 2.7x10-8 M) [62]
henatinib Hs Inhibition 7.6 pIC50 11
pIC50 7.6 (IC50 2.7x10-8 M) [11]
fruquintinib Hs Inhibition 7.5 – 7.6 pIC50 65
pIC50 7.6 (IC50 2.5x10-8 M) [65]
Description: Evaluated in a Z-lyte assay.
pIC50 7.5 (IC50 3.5x10-8 M) [65]
Description: Evaluated in a [32]p-ATP incorporation assay
pazopanib Hs Inhibition 7.5 pIC50 30
pIC50 7.5 (IC50 3x10-8 M) [30]
BLU-667 Hs Inhibition 7.5 pIC50 60
pIC50 7.5 (IC50 3.5x10-8 M) [60]
Description: In a biochemical assay.
ENMD-2076 Hs Inhibition 7.4 pIC50 54
pIC50 7.4 (IC50 3.6x10-8 M) [54]
erdafitinib Hs Inhibition 7.4 pIC50 58
pIC50 7.4 (IC50 3.63x10-8 M) [58]
MK-2461 Hs Inhibition 7.4 pIC50 51
pIC50 7.4 (IC50 4.4x10-8 M) [51]
anlotinib Hs Inhibition 7.3 pIC50 10
pIC50 7.3 (IC50 4.5x10-8 M) [10]
Description: In vitro activity
SU-14813 Hs Inhibition 7.3 pIC50 53
pIC50 7.3 (IC50 5x10-8 M) [53]
BMS-690514 Hs Inhibition 7.3 pIC50 44
pIC50 7.3 (IC50 5x10-8 M) [44]
VEGF receptor 2 kinase inhibitor I Mm Inhibition 7.2 pIC50 64
pIC50 7.2 (IC50 7x10-8 M) [64]
VEGF receptor 2 kinase inhibitor II Hs Inhibition 7.2 pIC50 63
pIC50 7.2 (IC50 7x10-8 M) [63]
AEE788 Hs Inhibition 7.1 pIC50 69
pIC50 7.1 (IC50 7.7x10-8 M) [69]
sorafenib Hs Inhibition 7.1 pIC50 74,78
pIC50 7.1 (IC50 9x10-8 M) [78]
pIC50 7.1 (IC50 9x10-8 M) [74]
cenisertib Hs Inhibition 7.0 pIC50 14
pIC50 7.0 (IC50 9.5x10-8 M) [14]
Description: In a biochemical homogeneous time-resolved fluorescence (HTRF) kinase assay with an ATP concentration of 1 mM.
ZM-306416 Hs Inhibition 7.0 pIC50 32
pIC50 7.0 (IC50 1x10-7 M) [32]
telatinib Hs Inhibition >7.0 pIC50 17
pIC50 >7.0 (IC50 <1x10-7 M) [17]
mivavotinib Hs Inhibition 6.9 pIC50 40
pIC50 6.9 (IC50 1.35x10-7 M) [40]
Description: Measured in a caliper-based electrophoretic mobility shift assay.
AST-487 Hs Inhibition 6.8 pIC50 1
pIC50 6.8 (IC50 1.7x10-7 M) [1]
Description: In vitro inhibition of KDR.
infigratinib Hs Inhibition 6.7 pIC50 29
pIC50 6.7 (IC50 1.8x10-7 M) [29]
semaxanib Hs Inhibition 6.7 pIC50 9
pIC50 6.7 (IC50 2x10-7 M) [9]
BX-912 Hs Inhibition 6.4 pIC50 20
pIC50 6.4 (IC50 4.1x10-7 M) [20]
pexidartinib Hs Inhibition 6.4 pIC50 66
pIC50 6.4 (IC50 4.4x10-7 M) [66]
orantinib Hs Inhibition 6.2 pIC50 35
pIC50 6.2 (IC50 6.8x10-7 M) [35]
DMBI Mm Inhibition 6.1 pIC50 71
pIC50 6.1 (IC50 7.94x10-7 M) [71]
compound 19a [PMID: 30503936] Hs Inhibition 6.1 pIC50 55
pIC50 6.1 (IC50 8.5x10-7 M) [55]
lazertinib Hs Inhibition <6.0 pIC50 61
pIC50 <6.0 (IC50 >1x10-6 M) [61]
Description: In a biochemical enzyme activity assay.
BX-795 Hs Inhibition 6.0 pIC50 20
pIC50 6.0 (IC50 1.1x10-6 M) [20]
GSK2646264 Hs Potentiation 4.5 pIC50 6
pIC50 4.5 (IC50 3.162x10-5 M) [6]
dovitinib Hs Inhibition - pIC50 56,70
pIC50 (IC50 6.5x10-8 – 1.3x10-8 M) [56,70]
compound T.14 Hs Inhibition - - 13
[13]
View species-specific inhibitor tables
Inhibitor Comments
Note that pazopanib is a multi-target kinase inhibitor. See [30] for additional data.
Vandetanib also inhibits EGFR and RET tyrosine kinases, as well as VEGFR2.
Although LY2874455 has equipotent IC50s for FGFRs and VEGFR2 in biochemical assays, in vivo efficacy appears to be 6-9-fold less for VEGFR2 phosphorylation in mouse heart muscle compared to inhibition of FGFR phosphorylation [79].
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
VEGFA {Sp: Human} Hs Agonist 8.0 – 9.6 pKd 38
pKd 9.6 (Kd 2.3x10-10 M) [38]
Description: Dissociation constant for scVEGF-binding to dimeric VEGFR2.
pKd 8.0 (Kd 1x10-8 M) [38]
Description: Dissociation constant for scVEGF-binding to monomeric VEGFR2.
Agonist Comments
Note that a VEGFA mimetic probe peptide (scVEGF) was used to determine the dissociation constants in the table above.
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
ramucirumab Hs Antagonist 10.3 pKd 42
pKd 10.3 (Kd 5x10-11 M) [42]
ramucirumab Hs Antagonist 9.0 pIC50 42
pIC50 9.0 (IC50 1x10-9 M) [42]
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 15,76

Key to terms and symbols Click column headers to sort
Target used in screen: VEGFR2
Ligand Sp. Type Action Value Parameter
cediranib Hs Inhibitor Inhibition 9.0 pKd
sunitinib Hs Inhibitor Inhibition 8.8 pKd
SU-14813 Hs Inhibitor Inhibition 8.6 pKd
brivanib Hs Inhibitor Inhibition 8.3 pKd
axitinib Hs Inhibitor Inhibition 8.2 pKd
linifanib Hs Inhibitor Inhibition 8.1 pKd
foretinib Hs Inhibitor Inhibition 7.9 pKd
pazopanib Hs Inhibitor Inhibition 7.8 pKd
Ki-20227 Hs Inhibitor Inhibition 7.7 pKd
motesanib Hs Inhibitor Inhibition 7.6 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx


Reference: 3,24

Key to terms and symbols Click column headers to sort
Target used in screen: KDR/KDR(VEGFR2)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
PDK1/Akt/Flt dual pathway inhibitor Hs Inhibitor Inhibition 1.9 109.0 104.0
SB 218078 Hs Inhibitor Inhibition 4.5 38.0 18.0
staurosporine Hs Inhibitor Inhibition 4.5 1.5 0.5
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 6.5 0.0 0.0
TWS119 Hs Inhibitor Inhibition 6.7 5.0 2.0
vandetanib Hs Inhibitor Inhibition 12.6
SU11652 Hs Inhibitor Inhibition 13.8 2.0 1.0
pazopanib Hs Inhibitor Inhibition 16.9
VEGF receptor tyrosine kinase inhibitor III Hs Inhibitor Inhibition 19.7
K-252a Hs Inhibitor Inhibition 20.0 3.0 0.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Hemangioma, capillary infantile
Synonyms: Familial capillary hemangioma [Orphanet: ORPHA91415]
OMIM: 602089
Orphanet: ORPHA91415
General Comments
This protein contains an immunoglobulin (Ig)-like domain that resembles the antibody variable domain, that has been coined the 'V-set domain'. The genes for all human V-set domain containing proteins are listed in HGNC gene group 590.

References

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