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kinase insert domain receptor

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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

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 1356 4q12 KDR kinase insert domain receptor
Mouse 1 1367 5 40.23 cM Kdr kinase insert domain protein receptor
Rat 1 1343 14p11 Kdr kinase insert domain receptor
Previous and Unofficial Names Click here for help
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 Click here for help
Alphafold P35968 (Hs), P35918 (Mm), O08775 (Rn)
BRENDA 2.7.10.1
CATH/Gene3D 2.60.40.10
ChEMBL Target CHEMBL279 (Hs), CHEMBL3337 (Mm)
DrugBank Target P35968 (Hs)
Ensembl Gene ENSG00000128052 (Hs), ENSMUSG00000062960 (Mm), ENSRNOG00000046829 (Rn)
Entrez Gene 3791 (Hs), 16542 (Mm), 25589 (Rn)
Human Protein Atlas ENSG00000128052 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:3791 (Hs), mmu:16542 (Mm), rno:25589 (Rn)
OMIM 191306 (Hs)
Orphanet ORPHA229801 (Hs)
Pharos P35968 (Hs)
RefSeq Nucleotide NM_002253 (Hs), NM_010612 (Mm), NM_013062 (Rn)
RefSeq Protein NP_002244 (Hs), NP_034742 (Mm), NP_037194 (Rn)
SynPHARM 78759 (in complex with axitinib)
81169 (in complex with axitinib)
79689 (in complex with lenvatinib)
79677 (in complex with nintedanib)
81175 (in complex with sorafenib)
81305 (in complex with sorafenib)
81287 (in complex with sunitinib)
79680 (in complex with tivozanib)
UniProtKB P35968 (Hs), P35918 (Mm), O08775 (Rn)
Wikipedia KDR (Hs)
Selected 3D Structures Click here for help
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:  49
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:  48
Enzyme Reaction Click here for help
EC Number: 2.7.10.1
Natural/Endogenous Ligands Click here for help
VEGFA {Sp: Human}
VEGFC {Sp: Human}
VEGFE {Sp: Human}

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
pegdinetanib Peptide Hs Inhibition ~9.0 pKd 28
⤷ pKd ~9.0 (Kd ~1x10-9 M) [28]
cediranib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.0 pKd 16
⤷ pKd 9.0 (Kd 1.1x10-9 M) [16]
SU-14813 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.6 pKd 16
⤷ pKd 8.6 (Kd 2.3x10-9 M) [16]
motesanib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.6 pKd 16
⤷ pKd 8.6 (Kd 2.6x10-9 M) [16]
BIBF-1202 Small molecule or natural product Hs Inhibition 8.5 pKd 16
⤷ pKd 8.5 (Kd 2.9x10-9 M) [16]
axitinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pKd 16
⤷ pKd 8.2 (Kd 5.9x10-9 M) [16]
pazopanib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.8 pKd 16
⤷ pKd 7.8 (Kd 1.4x10-8 M) [16]
RG-1530 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.8 pKd 74
⤷ pKd 7.8 (Kd 1.5x10-8 M) [74]
sorafenib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.2 pKd 16
⤷ pKd 7.2 (Kd 5.9x10-8 M) [16]
vatalanib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.2 pKd 16
⤷ pKd 7.2 (Kd 6.2x10-8 M) [16]
toceranib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pKi 44
⤷ pKi 8.2 (Ki 6x10-9 M) [44]
PLX-4720 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pKi 50
⤷ pKi 8.1 (Ki 9x10-9 M) [50]
pamufetinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pKi 24
⤷ pKi 7.9 (Ki 1.2x10-8 M) [24]
VEGF receptor tyrosine kinase inhibitor II Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.8 pKi 17
⤷ pKi 7.8 (Ki 1.5x10-8 M) [17]
cabozantinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 10.5 pIC50 85
⤷ pIC50 10.5 (IC50 3.5x10-11 M) [85]
tivozanib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.8 pIC50 51
⤷ pIC50 9.8 (IC50 1.6x10-10 M) [51]
axitinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.6 pIC50 42
⤷ pIC50 9.6 (IC50 2.5x10-10 M) [42]
canlitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.4 pIC50 71
⤷ pIC50 9.4 (IC50 3.8x10-10 M) [71]
cediranib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition >9.0 pIC50 79
⤷ pIC50 >9.0 (IC50 <1x10-9 M) [79]
VEGF receptor tyrosine kinase inhibitor III Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.0 pIC50 20
⤷ pIC50 9.0 (IC50 1x10-9 M) [20]
rivoceranib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 9.0 pIC50 73
⤷ pIC50 9.0 (IC50 1x10-9 M) [73]
Description: Assay used apatinib mesylate (YN968D1)
tesevatinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.8 pIC50 27
⤷ pIC50 8.8 (IC50 1.5x10-9 M) [27]
compound 13a [PMID: 23639540] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.8 pIC50 19
⤷ pIC50 8.8 (IC50 1.68x10-9 M) [19]
MLKL compound 1 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pIC50 60
⤷ pIC50 8.7 (IC50 2x10-9 M) [60]
ilorasertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 29
⤷ pIC50 8.7 (IC50 2x10-9 M) [29]
Description: Measuring inhibition of kinase activity in a biochemical assay.
foretinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 – 9.1 pIC50 51
⤷ pIC50 8.2 – 9.1 (IC50 6.8x10-9 – 8x10-10 M) [51]
tinengotinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.6 pIC50 83
⤷ pIC50 8.6 (IC50 2.5x10-9 M) [83]
motesanib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pIC50 51
⤷ pIC50 8.5 (IC50 3x10-9 M) [51]
compound 8i [PMID: 22765894] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 – 8.6 pIC50 38,86
⤷ pIC50 8.6 (IC50 2.6x10-9 M) [86]
pIC50 8.4 (IC50 4x10-9 M) [38]
dorsomorphin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pIC50 46
⤷ pIC50 8.4 (IC50 4x10-9 M) [46]
Description: Assayed using AMPK heterotrimeric complex containing α2, β1, γ1 subunits
linifanib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 3
⤷ pIC50 8.4 (IC50 4x10-9 M) [3]
lenvatinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pIC50 51
⤷ pIC50 8.4 (IC50 4x10-9 M) [51]
lucitanib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pIC50 88
⤷ pIC50 8.4 (IC50 4x10-9 M) [88]
CEP-11981 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 35
⤷ pIC50 8.4 (IC50 4x10-9 M) [35]
compound 8h [PMID: 22765894] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 38
⤷ pIC50 8.4 (IC50 4.2x10-9 M) [38]
famitinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.3 pIC50 12
⤷ pIC50 8.3 (IC50 5x10-9 M) [12]
sitravatinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pIC50 55
⤷ pIC50 8.3 (IC50 5x10-9 M) [55]
Description: In a biochemical enzyme activity assay.
tafetinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pIC50 78
⤷ pIC50 8.3 (IC50 5x10-9 M) [78]
Description: In a radiometric biochemical protein kinase assay.
soxataltinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pIC50 63
⤷ pIC50 8.3 (IC50 5.6x10-9 M) [63]
Description: Inhibition of KDR kinase activity in vitro.
LY2874455 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 87
⤷ pIC50 8.1 (IC50 7x10-9 M) [87]
Description: In vitro biochemical assay result
ibcasertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 89
⤷ pIC50 8.1 (IC50 7x10-9 M) [89]
Description: Inhibition in a biochemical assay.
OSI-930 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 26
⤷ pIC50 8.1 (IC50 9x10-9 M) [26]
altiratinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Hs Inhibition 8.0 pIC50 22
⤷ pIC50 8.0 (IC50 9.2x10-9 M) [22]
vandetanib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.0 pIC50 32
⤷ pIC50 8.0 (IC50 9x10-9 M) [32]
glesatinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 pIC50 13
⤷ pIC50 8.0 (IC50 1x10-8 M) [13]
CP-547632 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.0 pIC50 8
⤷ pIC50 8.0 (IC50 1.1x10-8 M) [8]
Ki-20227 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pIC50 53
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [53]
PP121 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.9 pIC50 5
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [5]
regorafenib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 7.9 pIC50 81
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [81]
golvatinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 pIC50 52
⤷ pIC50 7.8 (IC50 1.6x10-8 M) [52]
Description: Measured as inhibition of VEGFR-2 autophosphorylation in HUVEC cells.
acrizanib Small molecule or natural product Hs Inhibition 7.8 pIC50 1
⤷ pIC50 7.8 (IC50 1.74x10-8 M) [1]
Description: Determined in a Ba/F3 VEGFR2 cellular proliferation assay
VEGF receptor 2 kinase inhibitor IV Small molecule or natural product Primary target of this compound Hs Inhibition 7.7 pIC50 23
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [23]
SU5402 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 68
⤷ pIC50 7.7 (IC50 2x10-8 M) [68]
vatalanib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.7 pIC50 40
⤷ pIC50 7.7 (IC50 2.1x10-8 M) [40]
nintedanib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 34
⤷ pIC50 7.7 (IC50 2.1x10-8 M) [34]
surufatinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 62
⤷ pIC50 7.7 (IC50 2.1x10-8 M) [62]
Description: In a biochemical assay using recombinant KDR kinase catalytic domain.
resencatinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 63
⤷ pIC50 7.7 (IC50 2.17x10-8 M) [63]
sunitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 37
⤷ pIC50 7.7 (IC50 2.26x10-8 M) [37]
fexagratinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pIC50 6
⤷ pIC50 7.6 (IC50 2.4x10-8 M) [6]
brivanib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.6 pIC50 9
⤷ pIC50 7.6 (IC50 2.5x10-8 M) [9]
SU11652 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pIC50 66
⤷ pIC50 7.6 (IC50 2.7x10-8 M) [66]
henatinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 12
⤷ pIC50 7.6 (IC50 2.7x10-8 M) [12]
fruquintinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.5 – 7.6 pIC50 70
⤷ pIC50 7.6 (IC50 2.5x10-8 M) [70]
Description: Evaluated in a Z-lyte assay.
pIC50 7.5 (IC50 3.5x10-8 M) [70]
Description: Evaluated in a [32]p-ATP incorporation assay
pazopanib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.5 pIC50 31
⤷ pIC50 7.5 (IC50 3x10-8 M) [31]
pralsetinib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 7.5 pIC50 64
⤷ pIC50 7.5 (IC50 3.5x10-8 M) [64]
Description: In a biochemical assay.
ENMD-2076 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pIC50 57
⤷ pIC50 7.4 (IC50 3.6x10-8 M) [57]
erdafitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pIC50 61
⤷ pIC50 7.4 (IC50 3.63x10-8 M) [61]
ningetinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 pIC50 84
⤷ pIC50 7.4 (IC50 3.7x10-8 M) [84]
MK-2461 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 pIC50 54
⤷ pIC50 7.4 (IC50 4.4x10-8 M) [54]
catequentinib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 7.3 pIC50 11
⤷ pIC50 7.3 (IC50 4.5x10-8 M) [11]
Description: In vitro activity
SU-14813 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.3 pIC50 56
⤷ pIC50 7.3 (IC50 5x10-8 M) [56]
BMS-690514 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.3 pIC50 47
⤷ pIC50 7.3 (IC50 5x10-8 M) [47]
VEGF receptor 2 kinase inhibitor I Small molecule or natural product Primary target of this compound Mm Inhibition 7.2 pIC50 69
⤷ pIC50 7.2 (IC50 7x10-8 M) [69]
VEGF receptor 2 kinase inhibitor II Small molecule or natural product Primary target of this compound Hs Inhibition 7.2 pIC50 67
⤷ pIC50 7.2 (IC50 7x10-8 M) [67]
AEE788 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.1 pIC50 75
⤷ pIC50 7.1 (IC50 7.7x10-8 M) [75]
sorafenib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.1 pIC50 80,86
⤷ pIC50 7.1 (IC50 9x10-8 M) [80]
pIC50 7.1 (IC50 9x10-8 M) [86]
cenisertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.0 pIC50 15
⤷ pIC50 7.0 (IC50 9.5x10-8 M) [15]
Description: In a biochemical homogeneous time-resolved fluorescence (HTRF) kinase assay with an ATP concentration of 1 mM.
ZM-306416 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.0 pIC50 33
⤷ pIC50 7.0 (IC50 1x10-7 M) [33]
telatinib Small molecule or natural product Hs Inhibition >7.0 pIC50 18
⤷ pIC50 >7.0 (IC50 <1x10-7 M) [18]
mivavotinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.9 pIC50 41
⤷ pIC50 6.9 (IC50 1.35x10-7 M) [41]
Description: Measured in a caliper-based electrophoretic mobility shift assay.
AST-487 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pIC50 2
⤷ pIC50 6.8 (IC50 1.7x10-7 M) [2]
Description: In vitro inhibition of KDR.
infigratinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.7 pIC50 30
⤷ pIC50 6.7 (IC50 1.8x10-7 M) [30]
dual VEGFR/PARP inhibitor 14b Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.7 pIC50 43
⤷ pIC50 6.7 (IC50 1.906x10-7 M) [43]
semaxanib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.7 pIC50 10
⤷ pIC50 6.7 (IC50 2x10-7 M) [10]
BX-912 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pIC50 21
⤷ pIC50 6.4 (IC50 4.1x10-7 M) [21]
pexidartinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.4 pIC50 72
⤷ pIC50 6.4 (IC50 4.4x10-7 M) [72]
orantinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 pIC50 36
⤷ pIC50 6.2 (IC50 6.8x10-7 M) [36]
DMBI Small molecule or natural product Primary target of this compound Mm Inhibition 6.1 pIC50 77
⤷ pIC50 6.1 (IC50 7.94x10-7 M) [77]
compound 19a [PMID: 30503936] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.1 pIC50 58
⤷ pIC50 6.1 (IC50 8.5x10-7 M) [58]
lazertinib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition <6.0 pIC50 65
⤷ pIC50 <6.0 (IC50 >1x10-6 M) [65]
Description: In a biochemical enzyme activity assay.
BX-795 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.0 pIC50 21
⤷ pIC50 6.0 (IC50 1.1x10-6 M) [21]
GSK2646264 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 4.5 pIC50 7
⤷ pIC50 4.5 (IC50 3.162x10-5 M) [7]
dovitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition - pIC50 59,76
⤷ pIC50 (IC50 6.5x10-8 – 1.3x10-8 M) [59,76]
compound T.14 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition - - 14
⤷ [14]
View species-specific inhibitor tables
Inhibitor Comments
Note that pazopanib is a multi-target kinase inhibitor. See [31] 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 [87].
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
VEGFA {Sp: Human} Peptide Click here for species-specific activity table Hs Agonist 8.0 – 9.6 pKd 39
⤷ pKd 9.6 (Kd 2.3x10-10 M) [39]
Description: Dissociation constant for scVEGF-binding to dimeric VEGFR2.
pKd 8.0 (Kd 1x10-8 M) [39]
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 Peptide Approved drug Primary target of this compound Hs Antagonist 10.3 pKd 45
⤷ pKd 10.3 (Kd 5x10-11 M) [45]
ramucirumab Peptide Approved drug Primary target of this compound Hs Antagonist 9.0 pIC50 45
⤷ pIC50 9.0 (IC50 1x10-9 M) [45]
DiscoveRx KINOMEscan® screen Click here for help
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: 16,82
Key to terms and symbols Click column headers to sort
Target used in screen: VEGFR2
Ligand Sp. Type Action Value Parameter
cediranib Small molecule or natural product Hs Inhibitor Inhibition 9.0 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.8 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 8.6 pKd
brivanib Small molecule or natural product Hs Inhibitor Inhibition 8.3 pKd
axitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.2 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 8.1 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.9 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 7.8 pKd
Ki-20227 Small molecule or natural product Hs Inhibitor Inhibition 7.7 pKd
motesanib Small molecule or natural product Ligand has a PDB structure 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 Click here for help
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: 4,25
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 Small molecule or natural product Hs Inhibitor Inhibition 1.9 109.0 104.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 4.5 38.0 18.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.5 1.5 0.5
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 0.0 0.0
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 6.7 5.0 2.0
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 12.6
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 13.8 2.0 1.0
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 16.9
VEGF receptor tyrosine kinase inhibitor III Small molecule or natural product Hs Inhibitor Inhibition 19.7
K-252a Small molecule or natural product Hs Inhibitor Inhibition 20.0 3.0 0.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Immune system development
Immuno Process:  Immune regulation
Clinically-Relevant Mutations and Pathophysiology Click here for help
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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1. Adams CM, Anderson K, Artman 3rd G, Bizec JC, Cepeda R, Elliott J, Fassbender E, Ghosh M, Hanks S, Hardegger LA et al.. (2018) The Discovery of N-(1-Methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-((6- ((methylamino)methyl)pyrimidin-4-yl)oxy)-1H-indole-1-carboxamide (Acrizanib), a VEGFR-2 Inhibitor Specifically Designed for Topical Ocular Delivery, as a Therapy for Neovascular Age-Related Macular Degeneration. J Med Chem, 61 (4): 1622-1635. [PMID:29400470]

2. Akeno-Stuart N, Croyle M, Knauf JA, Malaguarnera R, Vitagliano D, Santoro M, Stephan C, Grosios K, Wartmann M, Cozens R et al.. (2007) The RET kinase inhibitor NVP-AST487 blocks growth and calcitonin gene expression through distinct mechanisms in medullary thyroid cancer cells. Cancer Res, 67 (14): 6956-64. [PMID:17638907]

3. Albert DH, Tapang P, Magoc TJ, Pease LJ, Reuter DR, Wei RQ, Li J, Guo J, Bousquet PF, Ghoreishi-Haack NS et al.. (2006) Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther, 5 (4): 995-1006. [PMID:16648571]

4. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]

5. Apsel B, Blair JA, Gonzalez B, Nazif TM, Feldman ME, Aizenstein B, Hoffman R, Williams RL, Shokat KM, Knight ZA. (2008) Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol, 4 (11): 691-9. [PMID:18849971]

6. AstraZeneca. AZD4547. Accessed on 11/09/2014. Modified on 11/09/2014. astrazeneca.com, http://openinnovation.astrazeneca.com/what-we-offer/compound/azd4547/

7. Barker MD, Liddle J, Atkinson FL, Wilson DM, Dickson MC, Ramirez-Molina C, Lewis H, Davis RP, Somers DO, Neu M et al.. (2018) Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease. Bioorg Med Chem Lett, 28 (21): 3458-3462. [PMID:30249354]

8. Beebe JS, Jani JP, Knauth E, Goodwin P, Higdon C, Rossi AM, Emerson E, Finkelstein M, Floyd E, Harriman S et al.. (2003) Pharmacological characterization of CP-547,632, a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for cancer therapy. Cancer Res, 63 (21): 7301-9. [PMID:14612527]

9. Bhide RS, Cai ZW, Zhang YZ, Qian L, Wei D, Barbosa S, Lombardo LJ, Borzilleri RM, Zheng X, Wu LI et al.. (2006) Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor. J Med Chem, 49 (7): 2143-6. [PMID:16570908]

10. Bold G, Altmann KH, Frei J, Lang M, Manley PW, Traxler P, Wietfeld B, Brüggen J, Buchdunger E, Cozens R et al.. (2000) New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis. J Med Chem, 43 (12): 2310-23. [PMID:10882357]

11. Chen GP. (2008) Spiro substituted compounds as angiogenesis inhibitors. Patent number: WO2008112407 A1. Assignee: Advenchen Laboratories, Llc. Priority date: 14/03/2007. Publication date: 18/09/2008.

12. Cho TP, Dong SY, Jun F, Hong FJ, Liang YJ, Lu X, Hua PJ, Li LY, Lei Z, Bing H et al.. (2010) Novel potent orally active multitargeted receptor tyrosine kinase inhibitors: synthesis, structure-activity relationships, and antitumor activities of 2-indolinone derivatives. J Med Chem, 53 (22): 8140-9. [PMID:21028894]

13. Claridge S, Raeppel F, Granger MC, Bernstein N, Saavedra O, Zhan L, Llewellyn D, Wahhab A, Deziel R, Rahil J et al.. (2008) Discovery of a novel and potent series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases. Bioorg Med Chem Lett, 18 (9): 2793-8. [PMID:18434145]

14. Conesa-Milián L, Falomir E, Murga J, Carda M, Marco JA. (2019) Novel multitarget inhibitors with antiangiogenic and immunomodulator properties. Eur J Med Chem, 170: 87-98. [PMID:30878834]

15. Curtin ML, Heyman HR, Frey RR, Marcotte PA, Glaser KB, Jankowski JR, Magoc TJ, Albert DH, Olson AM, Reuter DR et al.. (2012) Pyrazole diaminopyrimidines as dual inhibitors of KDR and Aurora B kinases. Bioorg Med Chem Lett, 22 (14): 4750-5. [PMID:22695126]

16. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

17. Dominguez C, Smith L, Huang Q, Yuan C, Ouyang X, Cai L, Chen P, Kim J, Harvey T, Syed R et al.. (2007) Discovery of N-phenyl nicotinamides as potent inhibitors of Kdr. Bioorg Med Chem Lett, 17 (21): 6003-8. [PMID:17869515]

18. Dumas JP, Joe TK, Kluender HCE, Lee W, Nagarantham D, Sibley RN, Su S, Boyer SJ, Dixon JA. (2001) Substituted pyridines and pyridazines with angiogenesis inhibiting activity. Patent number: WO2001023375A2. Assignee: Bayer Corporation. Priority date: 28/09/1999. Publication date: 05/04/2001.

19. Engers DW, Frist AY, Lindsley CW, Hong CC, Hopkins CR. (2013) Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe. Bioorg Med Chem Lett, 23 (11): 3248-52. [PMID:23639540]

20. Fedorov O, Marsden B, Pogacic V, Rellos P, Müller S, Bullock AN, Schwaller J, Sundström M, Knapp S. (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci USA, 104 (51): 20523-8. [PMID:18077363]

21. Feldman RI, Wu JM, Polokoff MA, Kochanny MJ, Dinter H, Zhu D, Biroc SL, Alicke B, Bryant J, Yuan S et al.. (2005) Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J Biol Chem, 280 (20): 19867-74. [PMID:15772071]

22. Flynn DL, Kaufman MD, Smith BD. (2016) Inhibition of tumor cell interactions with the microenvironment resulting in a reduction in tumor growth and disease progression. Patent number: WO2016061231. Assignee: Deciphera Pharmaceuticals, Llc. Priority date: 14/10/2014. Publication date: 21/04/2016.

23. Fraley ME, Rubino RS, Hoffman WF, Hambaugh SR, Arrington KL, Hungate RW, Bilodeau MT, Tebben AJ, Rutledge RZ, Kendall RL et al.. (2002) Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors: improvements in physical properties enhance cellular activity and pharmacokinetics. Bioorg Med Chem Lett, 12 (24): 3537-41. [PMID:12443771]

24. Fujita H, Miyadera K, Kato M, Fujioka Y, Ochiiwa H, Huang J, Ito K, Aoyagi Y, Takenaka T, Suzuki T et al.. (2013) The novel VEGF receptor/MET-targeted kinase inhibitor TAS-115 has marked in vivo antitumor properties and a favorable tolerability profile. Mol Cancer Ther, 12 (12): 2685-96. [PMID:24140932]

25. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]

26. Garton AJ, Crew AP, Franklin M, Cooke AR, Wynne GM, Castaldo L, Kahler J, Winski SL, Franks A, Brown EN et al.. (2006) OSI-930: a novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models. Cancer Res, 66 (2): 1015-24. [PMID:16424037]

27. Gendreau SB, Ventura R, Keast P, Laird AD, Yakes FM, Zhang W, Bentzien F, Cancilla B, Lutman J, Chu F et al.. (2007) Inhibition of the T790M gatekeeper mutant of the epidermal growth factor receptor by EXEL-7647. Clin Cancer Res, 13 (12): 3713-23. [PMID:17575237]

28. Getmanova EV, Chen Y, Bloom L, Gokemeijer J, Shamah S, Warikoo V, Wang J, Ling V, Sun L. (2006) Antagonists to human and mouse vascular endothelial growth factor receptor 2 generated by directed protein evolution in vitro. Chem Biol, 13 (5): 549-56. [PMID:16720276]

29. Glaser KB, Li J, Marcotte PA, Magoc TJ, Guo J, Reuter DR, Tapang P, Wei RQ, Pease LJ, Bui MH et al.. (2012) Preclinical characterization of ABT-348, a kinase inhibitor targeting the aurora, vascular endothelial growth factor receptor/platelet-derived growth factor receptor, and Src kinase families. J Pharmacol Exp Ther, 343 (3): 617-27. [PMID:22935731]

30. Guagnano V, Furet P, Spanka C, Bordas V, Le Douget M, Stamm C, Brueggen J, Jensen MR, Schnell C, Schmid H et al.. (2011) Discovery of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase. J Med Chem, 54 (20): 7066-83. [PMID:21936542]

31. Harris PA, Boloor A, Cheung M, Kumar R, Crosby RM, Davis-Ward RG, Epperly AH, Hinkle KW, Hunter 3rd RN, Johnson JH et al.. (2008) Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor. J Med Chem, 51 (15): 4632-40. [PMID:18620382]

32. Harris PA, Cheung M, Hunter 3rd RN, Brown ML, Veal JM, Nolte RT, Wang L, Liu W, Crosby RM, Johnson JH et al.. (2005) Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors. J Med Chem, 48 (5): 1610-9. [PMID:15743202]

33. Hennequin LF, Thomas AP, Johnstone C, Stokes ES, Plé PA, Lohmann JJ, Ogilvie DJ, Dukes M, Wedge SR, Curwen JO et al.. (1999) Design and structure-activity relationship of a new class of potent VEGF receptor tyrosine kinase inhibitors. J Med Chem, 42 (26): 5369-89. [PMID:10639280]

34. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J et al.. (2008) BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res, 68 (12): 4774-82. [PMID:18559524]

35. Hudkins RL, Becknell NC, Zulli AL, Underiner TL, Angeles TS, Aimone LD, Albom MS, Chang H, Miknyoczki SJ, Hunter K et al.. (2012) Synthesis and biological profile of the pan-vascular endothelial growth factor receptor/tyrosine kinase with immunoglobulin and epidermal growth factor-like homology domains 2 (VEGF-R/TIE-2) inhibitor 11-(2-methylpropyl)-12,13-dihydro-2-methyl-8-(pyrimidin-2-ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one (CEP-11981): a novel oncology therapeutic agent. J Med Chem, 55 (2): 903-13. [PMID:22148921]

36. Kammasud N, Boonyarat C, Sanphanya K, Utsintong M, Tsunoda S, Sakurai H, Saiki I, André I, Grierson DS, Vajragupta O. (2009) 5-Substituted pyrido[2,3-d]pyrimidine, an inhibitor against three receptor tyrosine kinases. Bioorg Med Chem Lett, 19 (3): 745-50. [PMID:19110422]

37. Khanwelkar RR, Chen GS, Wang HC, Yu CW, Huang CH, Lee O, Chen CH, Hwang CS, Ko CH, Chou NT et al.. (2010) Synthesis and structure-activity relationship of 6-arylureido-3-pyrrol-2-ylmethylideneindolin-2-one derivatives as potent receptor tyrosine kinase inhibitors. Bioorg Med Chem, 18 (13): 4674-86. [PMID:20570526]

38. Kim MH, Tsuhako AL, Co EW, Aftab DT, Bentzien F, Chen J, Cheng W, Engst S, Goon L, Klein RR et al.. (2012) The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett, 22 (15): 4979-85. [PMID:22765894]

39. King C, Hristova K. (2019) Direct measurements of VEGF-VEGFR2 binding affinities reveal the coupling between ligand binding and receptor dimerization. J Biol Chem, 294 (23): 9064-9075. [PMID:31023826]

40. Kiselyov AS, Semenova M, Semenov VV, Piatnitski E, Ouyang S. (2006) Hetaryl imidazoles: a novel dual inhibitors of VEGF receptors I and II. Bioorg Med Chem Lett, 16 (5): 1440-4. [PMID:16321531]

41. Lam B, Arikawa Y, Cramlett J, Dong Q, de Jong R, Feher V, Grimshaw CE, Farrell PJ, Hoffman ID, Jennings A et al.. (2016) Discovery of TAK-659 an orally available investigational inhibitor of Spleen Tyrosine Kinase (SYK). Bioorg Med Chem Lett, 26 (24): 5947-5950. [PMID:27839918]

42. Lee K, Jeong KW, Lee Y, Song JY, Kim MS, Lee GS, Kim Y. (2010) Pharmacophore modeling and virtual screening studies for new VEGFR-2 kinase inhibitors. Eur J Med Chem, 45 (11): 5420-7. [PMID:20869793]

43. Li Y, Liu Y, Zhang D, Chen J, Yang G, Tang P, Yang C, Liu J, Zhang J, Ouyang L. (2023) Discovery, Synthesis, and Evaluation of Novel Dual Inhibitors of a Vascular Endothelial Growth Factor Receptor and Poly(ADP-Ribose) Polymerase for BRCA Wild-Type Breast Cancer Therapy. J Med Chem, 66 (17): 12069-12100. [PMID:37616488]

44. Liao AT, Chien MB, Shenoy N, Mendel DB, McMahon G, Cherrington JM, London CA. (2002) Inhibition of constitutively active forms of mutant kit by multitargeted indolinone tyrosine kinase inhibitors. Blood, 100 (2): 585-93. [PMID:12091352]

45. Lu D, Shen J, Vil MD, Zhang H, Jimenez X, Bohlen P, Witte L, Zhu Z. (2003) Tailoring in vitro selection for a picomolar affinity human antibody directed against vascular endothelial growth factor receptor 2 for enhanced neutralizing activity. J Biol Chem, 278 (44): 43496-507. [PMID:12917408]

46. Machrouhi F, Ouhamou N, Laderoute K, Calaoagan J, Bukhtiyarova M, Ehrlich PJ, Klon AE. (2010) The rational design of a novel potent analogue of the 5'-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular activity. Bioorg Med Chem Lett, 20 (22): 6394-9. [PMID:20932747]

47. Marathe P, Tang Y, Sleczka B, Rodrigues D, Gavai A, Wong T, Christopher L, Zhang H. (2010) Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci, 99 (8): 3579-93. [PMID:20166197]

48. McTigue M, Murray BW, Chen JH, Deng YL, Solowiej J, Kania RS. (2012) Molecular conformations, interactions, and properties associated with drug efficiency and clinical performance among VEGFR TK inhibitors. Proc Natl Acad Sci USA, 109 (45): 18281-9. [PMID:22988103]

49. McTigue MA, Wickersham JA, Pinko C, Showalter RE, Parast CV, Tempczyk-Russell A, Gehring MR, Mroczkowski B, Kan CC, Villafranca JE et al.. (1999) Crystal structure of the kinase domain of human vascular endothelial growth factor receptor 2: a key enzyme in angiogenesis. Structure, 7 (3): 319-30. [PMID:10368301]

50. Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB et al.. (2003) In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res, 9 (1): 327-37. [PMID:12538485]

51. Musumeci F, Radi M, Brullo C, Schenone S. (2012) Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors. J Med Chem, 55 (24): 10797-822. [PMID:23098265]

52. Nakagawa T, Tohyama O, Yamaguchi A, Matsushima T, Takahashi K, Funasaka S, Shirotori S, Asada M, Obaishi H. (2010) E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. Cancer Sci, 101 (1): 210-5. [PMID:19832844]

53. Ohno H, Kubo K, Murooka H, Kobayashi Y, Nishitoba T, Shibuya M, Yoneda T, Isoe T. (2006) A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Mol Cancer Ther, 5 (11): 2634-43. [PMID:17121910]

54. Pan BS, Chan GK, Chenard M, Chi A, Davis LJ, Deshmukh SV, Gibbs JB, Gil S, Hang G, Hatch H et al.. (2010) MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res, 70 (4): 1524-33. [PMID:20145145]

55. Patwardhan PP, Ivy KS, Musi E, de Stanchina E, Schwartz GK. (2016) Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma. Oncotarget, 7 (4): 4093-109. [PMID:26675259]

56. Patyna S, Laird AD, Mendel DB, O'farrell AM, Liang C, Guan H, Vojkovsky T, Vasile S, Wang X, Chen J et al.. (2006) SU14813: a novel multiple receptor tyrosine kinase inhibitor with potent antiangiogenic and antitumor activity. Mol Cancer Ther, 5 (7): 1774-82. [PMID:16891463]

57. Pollard JR, Mortimore M. (2009) Discovery and development of aurora kinase inhibitors as anticancer agents. J Med Chem, 52 (9): 2629-51. [PMID:19320489]

58. Qi B, Yang Y, Gong G, He H, Yue X, Xu X, Hu Y, Li J, Chen T, Wan X et al.. (2019) Discovery of N1-(4-((7-(3-(4-ethylpiperazin-1-yl)propoxy)-6-methoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)-N3-(2-(2,6-difluorophenyl)-4-oxothiazolidin-3-yl)urea as a multi-tyrosine kinase inhibitor for drug-sensitive and drug-resistant cancers treatment. Eur J Med Chem, 163: 10-27. [PMID:30503936]

59. Renhowe PA, Pecchi S, Shafer CM, Machajewski TD, Jazan EM, Taylor C, Antonios-McCrea W, McBride CM, Frazier K, Wiesmann M et al.. (2009) Design, structure-activity relationships and in vivo characterization of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones: a novel class of receptor tyrosine kinase inhibitors. J Med Chem, 52 (2): 278-92. [PMID:19113866]

60. Sammond DM, Nailor KE, Veal JM, Nolte RT, Wang L, Knick VB, Rudolph SK, Truesdale AT, Nartey EN, Stafford JA et al.. (2005) Discovery of a novel and potent series of dianilinopyrimidineurea and urea isostere inhibitors of VEGFR2 tyrosine kinase. Bioorg Med Chem Lett, 15 (15): 3519-23. [PMID:15990302]

61. Saxty G, Murray CW, Berdini V, Besong GE, Hamlett CCF, Johnson CN, Woodhead SJ, Reader M, Rees DC, Mevellec LA et al.. (2011) Pyrazolyl quinazoline kinase inhibitors. Patent number: WO2011135376 A1. Assignee: Astex Therapeutics Limited. Priority date: 30/04/2010. Publication date: 03/11/2011.

62. Su W-G, Zhang W, Jia H, Cui Y, Ren Y, Sai Y, Wu Z, Li W, Shao J. (2011) Compound, certain novel forms thereof, pharmaceutical compositions thereof and methods for preparation and use. Patent number: WO2011060746. Assignee: Hutchison Medipharma Limited. Priority date: 23/11/2009. Publication date: 26/05/2011.

63. Su Y, Wang J, Bao R. (2020) Inhibitor containing bicyclic derivative, preparation method therefor and use thereof. Patent number: WO2020228756A1. Assignee: Shanghai Hansoh Biomedical Technology Co., Ltd., Jiangsu Hansoh Pharmaceutical Group Co., Ltd.. Priority date: 14/05/2020. Publication date: 19/11/2020.

64. Subbiah V, Gainor JF, Rahal R, Brubaker JD, Kim JL, Maynard M, Hu W, Cao Q, Sheets MP, Wilson D et al.. (2018) Precision Targeted Therapy with BLU-667 for RET-Driven Cancers. Cancer Discov, 8 (7): 836-849. [PMID:29657135]

65. Suh B-C, Salgaonkar PD, Lee J, Koh JS, Song H-J, Lee IY, Lee J, Jung DS, Kim J-H, Kim S-W. (2016) Compounds and compositions for modulating EGFR mutant kinase activities. Patent number: WO2016060443A2. Assignee: Yuhan Corporation. Priority date: 13/10/2014. Publication date: 21/04/2016.

66. Sun L, Liang C, Shirazian S, Zhou Y, Miller T, Cui J, Fukuda JY, Chu JY, Nematalla A, Wang X et al.. (2003) Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase. J Med Chem, 46 (7): 1116-9. [PMID:12646019]

67. Sun L, Tran N, Liang C, Hubbard S, Tang F, Lipson K, Schreck R, Zhou Y, McMahon G, Tang C. (2000) Identification of substituted 3-[(4,5,6, 7-tetrahydro-1H-indol-2-yl)methylene]-1,3-dihydroindol-2-ones as growth factor receptor inhibitors for VEGF-R2 (Flk-1/KDR), FGF-R1, and PDGF-Rbeta tyrosine kinases. J Med Chem, 43 (14): 2655-63. [PMID:10893303]

68. Sun L, Tran N, Liang C, Tang F, Rice A, Schreck R, Waltz K, Shawver LK, McMahon G, Tang C. (1999) Design, synthesis, and evaluations of substituted 3-[(3- or 4-carboxyethylpyrrol-2-yl)methylidenyl]indolin-2-ones as inhibitors of VEGF, FGF, and PDGF receptor tyrosine kinases. J Med Chem, 42 (25): 5120-30. [PMID:10602697]

69. Sun L, Tran N, Tang F, App H, Hirth P, McMahon G, Tang C. (1998) Synthesis and biological evaluations of 3-substituted indolin-2-ones: a novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases. J Med Chem, 41 (14): 2588-603. [PMID:9651163]

70. Sun Q, Zhou J, Zhang Z, Guo M, Liang J, Zhou F, Long J, Zhang W, Yin F, Cai H et al.. (2014) Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther, 15 (12): 1635-45. [PMID:25482937]

71. Sun X, Wang L, Yang H, Hu H. (2020) Crystal forms of compound, preparation method therefor, pharmaceutical composition and application thereof. Patent number: WO2020216188. Assignee: Beijing Kangchen Pharmaceutical Co., Ltd.. Priority date: 20/04/2020. Publication date: 29/10/2020.

72. Tap WD, Wainberg ZA, Anthony SP, Ibrahim PN, Zhang C, Healey JH, Chmielowski B, Staddon AP, Cohn AL, Shapiro GI et al.. (2015) Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor. N Engl J Med, 373 (5): 428-37. [PMID:26222558]

73. Tian S, Quan H, Xie C, Guo H, Lü F, Xu Y, Li J, Lou L. (2011) YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci, 102 (7): 1374-80. [PMID:21443688]

74. Tovar C, Higgins B, Deo D, Kolinsky K, Liu JJ, Heimbrook DC, Vassilev LT. (2010) Small-molecule inducer of cancer cell polyploidy promotes apoptosis or senescence: Implications for therapy. Cell Cycle, 9 (16): 3364-75. [PMID:20814247]

75. Traxler P, Allegrini PR, Brandt R, Brueggen J, Cozens R, Fabbro D, Grosios K, Lane HA, McSheehy P, Mestan J et al.. (2004) AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res, 64 (14): 4931-41. [PMID:15256466]

76. Trudel S, Li ZH, Wei E, Wiesmann M, Chang H, Chen C, Reece D, Heise C, Stewart AK. (2005) CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma. Blood, 105 (7): 2941-8. [PMID:15598814]

77. Vieth M, Cummins DJ. (2000) DoMCoSAR: a novel approach for establishing the docking mode that is consistent with the structure-activity relationship. Application to HIV-1 protease inhibitors and VEGF receptor tyrosine kinase inhibitors. J Med Chem, 43 (16): 3020-32. [PMID:10956210]

78. Wang D, Tang F, Wang S, Jiang Z, Zhang L. (2012) Preclinical anti-angiogenesis and anti-tumor activity of SIM010603, an oral, multi-targets receptor tyrosine kinases inhibitor. Cancer Chemother Pharmacol, 69 (1): 173-83. [PMID:21638122]

79. Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, Smith NR, James NH, Dukes M, Curwen JO et al.. (2005) AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res, 65 (10): 4389-400. [PMID:15899831]

80. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M et al.. (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res, 64 (19): 7099-109. [PMID:15466206]

81. Wilhelm SM, Dumas J, Adnane L, Lynch M, Carter CA, Schütz G, Thierauch KH, Zopf D. (2011) Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer, 129 (1): 245-55. [PMID:21170960]

82. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]

83. Wu F. (2021) Multi-kinase inhibitor compound, and crystal form and use thereof. Patent number: US10889586B2. Assignee: Nanjing Transthera Biosciences Co Ltd. Priority date: 13/12/2016. Publication date: 12/01/2021.

84. Xi N. (2015) Substituted quinoline compounds and methods of use. Patent number: US9133162B2. Assignee: Sunshine Lake Pharma Co Ltd, Calitor Sciences LLC. Priority date: 28/02/2011. Publication date: 15/09/2015.

85. Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B et al.. (2011) Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther, 10 (12): 2298-308. [PMID:21926191]

86. You WK, Sennino B, Williamson CW, Falcón B, Hashizume H, Yao LC, Aftab DT, McDonald DM. (2011) VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer. Cancer Res, 71 (14): 4758-68. [PMID:21613405]

87. Zhao G, Li WY, Chen D, Henry JR, Li HY, Chen Z, Zia-Ebrahimi M, Bloem L, Zhai Y, Huss K et al.. (2011) A novel, selective inhibitor of fibroblast growth factor receptors that shows a potent broad spectrum of antitumor activity in several tumor xenograft models. Mol Cancer Ther, 10 (11): 2200-10. [PMID:21900693]

88. Zhou Y, Chen Y, Tong L, Xie H, Wen W, Zhang J, Xi Y, Shen Y, Geng M, Wang Y et al.. (2012) AL3810, a multi-tyrosine kinase inhibitor, exhibits potent anti-angiogenic and anti-tumour activity via targeting VEGFR, FGFR and PDGFR. J Cell Mol Med, 16 (10): 2321-30. [PMID:22304225]

89. Zhou Y, Shan S, Li ZB, Xin LJ, Pan DS, Yang QJ, Liu YP, Yue XP, Liu XR, Gao JZ et al.. (2017) CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency. Cancer Sci, 108 (3): 469-477. [PMID:28004478]

How to cite this page

Type IV RTKs: VEGF (vascular endothelial growth factor) receptor family: kinase insert domain receptor. Last modified on 14/08/2024. Accessed on 19/03/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1813.