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fms related receptor tyrosine kinase 4

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Target not currently curated in GtoImmuPdb

Target id: 1814

Nomenclature: fms related receptor tyrosine kinase 4

Abbreviated Name: VEGFR-3

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 1363 5q35.3 FLT4 fms related receptor tyrosine kinase 4
Mouse 1 1363 11 29.69 cM Flt4 FMS-like tyrosine kinase 4
Rat 1 1363 10q21 Flt4 Fms related receptor tyrosine kinase 4
Previous and Unofficial Names Click here for help
fms related tyrosine kinase 4 | PCL | vascular endothelial growth factor receptor 3
Database Links Click here for help
Alphafold P35916 (Hs), P35917 (Mm), Q91ZT1 (Rn)
BRENDA 2.7.10.1
CATH/Gene3D 2.60.40.10
ChEMBL Target CHEMBL1955 (Hs), CHEMBL4758 (Mm)
DrugBank Target P35916 (Hs)
Ensembl Gene ENSG00000037280 (Hs), ENSMUSG00000020357 (Mm), ENSRNOG00000002511 (Rn)
Entrez Gene 2324 (Hs), 14257 (Mm), 114110 (Rn)
Human Protein Atlas ENSG00000037280 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:2324 (Hs), mmu:14257 (Mm), rno:114110 (Rn)
OMIM 136352 (Hs)
Orphanet ORPHA121872 (Hs)
Pharos P35916 (Hs)
RefSeq Nucleotide NM_002020 (Hs), NM_008029 (Mm), NM_053652 (Rn)
RefSeq Protein NP_002011 (Hs), NP_032055 (Mm), NP_446104 (Rn)
UniProtKB P35916 (Hs), P35917 (Mm), Q91ZT1 (Rn)
Wikipedia FLT4 (Hs)
Enzyme Reaction Click here for help
EC Number: 2.7.10.1
Natural/Endogenous Ligands Click here for help
VEGFC {Sp: Human}
VEGFD {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
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 9.6 pIC50 18
⤷ pIC50 9.6 (IC50 2.4x10-10 M) [18]
fruquintinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.3 pIC50 23
⤷ pIC50 9.3 (IC50 5x10-10 M) [23]
Description: Evaluated in a [32]p-ATP incorporation assay
catequentinib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 9.0 pIC50 4
⤷ pIC50 9.0 (IC50 1x10-9 M) [4]
Description: In vitro activity
sitravatinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 20
⤷ pIC50 8.7 (IC50 2x10-9 M) [20]
Description: In a biochemical enzyme activity assay.
foretinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.6 pIC50 18
⤷ pIC50 8.6 (IC50 2.8x10-9 M) [18]
cediranib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition >8.5 pIC50 26
⤷ pIC50 >8.5 (IC50 <3x10-9 M) [26]
compound 8i [PMID: 22765894] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 30
⤷ pIC50 8.5 (IC50 3x10-9 M) [30]
compound 8h [PMID: 22765894] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 13
⤷ pIC50 8.5 (IC50 3.2x10-9 M) [13]
dovitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 – 8.5 pIC50 21,24
⤷ pIC50 8.1 – 8.5 (IC50 8x10-9 – 3x10-9 M) [21,24]
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 8.3 pIC50 18
⤷ pIC50 8.3 (IC50 5.2x10-9 M) [18]
motesanib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pIC50 18
⤷ pIC50 8.2 (IC50 6x10-9 M) [18]
tesevatinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.1 pIC50 8
⤷ pIC50 8.1 (IC50 8.7x10-9 M) [8]
sunitinib 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 8.1 pIC50 12
⤷ pIC50 8.1 (IC50 8.9x10-9 M) [12]
ibcasertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 31
⤷ pIC50 8.1 (IC50 9x10-9 M) [31]
Description: Inhibition in a biochemical assay.
tafetinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pIC50 25
⤷ pIC50 7.9 (IC50 1.19x10-8 M) [25]
Description: In a radiometric biochemical protein kinase assay.
nintedanib 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 7.9 pIC50 11
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [11]
sorafenib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Mm Inhibition 7.7 pIC50 27
⤷ pIC50 7.7 (IC50 2x10-8 M) [27]
RIPK1 inhibitor 22b Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 14
⤷ pIC50 7.7 (IC50 2x10-8 M) [14]
pexmetinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 pIC50 3
⤷ pIC50 7.4 (IC50 4.2x10-8 M) [3]
ilorasertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 pIC50 9
⤷ pIC50 7.4 (IC50 4.3x10-8 M) [9]
Description: Measuring inhibition of kinase activity in a biochemical assay.
pazopanib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.3 pIC50 10
⤷ pIC50 7.3 (IC50 4.7x10-8 M) [10]
MK-2461 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 19
⤷ pIC50 7.1 (IC50 7.8x10-8 M) [19]
compound 38k [PMID: 34351741] Small molecule or natural product Hs Inhibition 7.0 pIC50 15
⤷ pIC50 7.0 (IC50 1.104x10-7 M) [15]
CHMFL-KIT-64 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.9 pIC50 29
⤷ pIC50 6.9 (IC50 1.21x10-7 M) [29]
Description: In a biochemical assay.
VEGF receptor tyrosine kinase inhibitor III Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.9 pIC50 6
⤷ pIC50 6.9 (IC50 1.25x10-7 M) [6]
linifanib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.7 pIC50 1
⤷ pIC50 6.7 (IC50 1.9x10-7 M) [1]
vatalanib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.7 pIC50 16
⤷ pIC50 6.7 (IC50 1.95x10-7 M) [16]
compound 25c [PMID: 36649216] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pIC50 22
⤷ pIC50 6.4 (IC50 4.23x10-7 M) [22]
onatasertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pIC50 17
⤷ pIC50 6.2 (IC50 6.51x10-7 M) [17]
View species-specific inhibitor tables
Inhibitor Comments
Note that pazopanib is a multi-target kinase inhibitor. See for [10] futher affinity data.
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: 5,28
Key to terms and symbols Click column headers to sort
Target used in screen: FLT4
Ligand Sp. Type Action Value Parameter
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.8 pKd
cediranib Small molecule or natural product Hs Inhibitor Inhibition 8.4 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.0 pKd
motesanib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 7.8 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.8 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 7.6 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.6 pKd
quizartinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 7.3 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: 2,7
Key to terms and symbols Click column headers to sort
Target used in screen: Flt4/FLT4
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Small molecule or natural product Hs Inhibitor Inhibition 2.5 0.0 1.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.7 0.0 -1.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.3 -0.5 0.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 5.0 0.0 2.0
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 5.1 2.0 0.0
PDK1/Akt/Flt dual pathway inhibitor Small molecule or natural product Hs Inhibitor Inhibition 5.8 98.0 70.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 10.9 1.0 3.0
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 11.3
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 12.1 0.0 0.0
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 12.1 0.0 1.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Hemangioma, capillary infantile
Synonyms: Familial capillary hemangioma [Orphanet: ORPHA91415]
OMIM: 602089
Orphanet: ORPHA91415
Disease:  Lymphedema, hereditary IA
Synonyms: Hereditary lymphedema [Disease Ontology: DOID:0050580]
Milroy disease [Orphanet: ORPHA79452]
Disease Ontology: DOID:0050580
OMIM: 153100
Orphanet: ORPHA79452

References

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How to cite this page

Type IV RTKs: VEGF (vascular endothelial growth factor) receptor family: fms related receptor tyrosine kinase 4. Last modified on 19/01/2023. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1814.