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fms related receptor tyrosine kinase 3

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Target id: 1807

Nomenclature: fms related receptor tyrosine kinase 3

Abbreviated Name: FLT3

Family: Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 993 13q12.2 FLT3 fms related receptor tyrosine kinase 3
Mouse 1 1000 5 G3 Flt3 FMS-like tyrosine kinase 3
Rat - 1000 12p11 Flt3 Fms related receptor tyrosine kinase 3
Previous and Unofficial Names Click here for help
CD135 | Fetal liver kinase 2 | FL cytokine receptor | FLK2 | FMS-like tyrosine kinase 3 | fms-related tyrosine kinase 3 | fms related tyrosine kinase 3 | STK1
Database Links Click here for help
Alphafold P36888 (Hs), Q00342 (Mm)
BRENDA 2.7.10.1
CATH/Gene3D 2.60.40.10
ChEMBL Target CHEMBL1974 (Hs), CHEMBL2034796 (Mm)
DrugBank Target P36888 (Hs)
Ensembl Gene ENSG00000122025 (Hs), ENSMUSG00000042817 (Mm), ENSRNOG00000054764 (Rn)
Entrez Gene 2322 (Hs), 14255 (Mm), 140635 (Rn)
Human Protein Atlas ENSG00000122025 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:2322 (Hs), mmu:14255 (Mm), rno:140635 (Rn)
OMIM 136351 (Hs)
Orphanet ORPHA138366 (Hs)
Pharos P36888 (Hs)
RefSeq Nucleotide NM_004119 (Hs), NM_010229 (Mm), NM_001100822 (Rn)
RefSeq Protein NP_004110 (Hs), NP_034359 (Mm), NP_001094292 (Rn)
UniProtKB P36888 (Hs), Q00342 (Mm)
Wikipedia FLT3 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of a human Flt3 ligand-receptor ternary complex
PDB Id:  3QS7
Resolution:  4.3Å
Species:  Human
References:  63
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of FLT3
PDB Id:  1RJB
Resolution:  2.1Å
Species:  Human
References:  25
Enzyme Reaction Click here for help
EC Number: 2.7.10.1
Natural/Endogenous Ligands Click here for help
Fms-related tyrosine kinase 3 ligand {Sp: Human}

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
AC710 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.3 pKd 39
⤷ pKd 9.3 (Kd 5x10-10 M) [39]
linifanib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.2 pKd 13
⤷ pKd 9.2 (Kd 6.3x10-10 M) [13]
dovitinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.2 pKd 13
⤷ pKd 9.2 (Kd 6.4x10-10 M) [13]
crenolanib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.1 pKd 27
⤷ pKd 9.1 (Kd 7.4x10-10 M) [27]
AST-487 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.1 pKd 13
⤷ pKd 9.1 (Kd 7.9x10-10 M) [13]
quizartinib 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 8.8 – 8.9 pKd 10,13
⤷ pKd 8.8 – 8.9 (Kd 1.6x10-9 – 1.3x10-9 M) [10,13]
compound 6li [Chan et al., 2022] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.6 pKd 9
⤷ pKd 8.6 (Kd 2.5x10-9 M) [9]
tandutinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.5 pKd 13
⤷ pKd 8.5 (Kd 3x10-9 M) [13]
compound 5e [PMID: 28580438] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.4 pKd 28
⤷ pKd 8.4 (Kd 3.6x10-9 M) [28]
Description: Measured using the Z′-LYTE Kinase Assay Kit and wild type FLT3.
lestaurtinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.1 pKd 13
⤷ pKd 8.1 (Kd 8.5x10-9 M) [13]
midostaurin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.0 pKd 13
⤷ pKd 8.0 (Kd 1.1x10-8 M) [13]
RG-1530 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 pKd 61
⤷ pKd 8.0 (Kd 1.1x10-8 M) [61]
KW-2449 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.8 pKd 13
⤷ pKd 7.8 (Kd 1.5x10-8 M) [13]
belizatinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pKd 38
⤷ pKd 7.4 (Kd 4.2x10-8 M) [38]
Description: Binding affinity in vitro.
UNC4203 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.8 pKi 81
⤷ pKi 7.8 (Ki 1.614x10-8 M) [81]
AST-487 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.9 pKi 68
⤷ pKi 6.9 (Ki 1.2x10-7 M) [68]
Description: Inhibition of wild type FLT3
nefextinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.5 – 9.7 pIC50 73
⤷ pIC50 9.7 (IC50 2x10-10 M) [73]
Description: Inhibitor potency for FLT3 D835Y mutant
pIC50 9.6 (IC50 2.8x10-10 M) [73]
Description: Inhibition potency for WT FLT3
pIC50 9.5 (IC50 3.4x10-10 M) [73]
Description: Inhibitor potency for FLT3-ITD fusion
gilteritinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition ~9.5 pIC50 36
⤷ pIC50 ~9.5 (IC50 ~3x10-10 M) [36]
denfivontinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.4 pIC50 35
⤷ pIC50 9.4 (IC50 4x10-10 M) [35]
Gö 6976 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.1 pIC50 77
⤷ pIC50 9.1 (IC50 7x10-10 M) [77]
Description: Inhibitory activity against recombinant FLT3 in an in vitro kinase assay.
TTT-3002 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.1 pIC50 41
⤷ pIC50 9.1 (IC50 7.2x10-10 M) [41]
Description: Inhibition of FLT3 phosphorylation in Molm14 human leukemia cells that carry the FLT3/ITD activation mutation
compound 8i [PMID: 22765894] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.1 pIC50 78
⤷ pIC50 9.1 (IC50 8x10-10 M) [78]
compound 8h [PMID: 22765894] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.1 pIC50 32
⤷ pIC50 9.1 (IC50 8.5x10-10 M) [32]
dorsomorphin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition >9.0 pIC50 42
⤷ pIC50 >9.0 (IC50 <1x10-9 M) [42]
Description: Assayed using AMPK heterotrimeric complex containing α2, β1, γ1 subunits
RGB-286638 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.0 pIC50 11
⤷ pIC50 9.0 (IC50 1x10-9 M) [11]
ilorasertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.0 pIC50 21
⤷ pIC50 9.0 (IC50 1x10-9 M) [21]
Description: Measuring inhibition of kinase activity in a biochemical assay.
tuspetinib Small molecule or natural product Hs Inhibition 9.0 pIC50 5
⤷ pIC50 9.0 (IC50 1.1x10-9 M) [5]
dovitinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.5 – 9.0 pIC50 56,62
⤷ pIC50 8.5 – 9.0 (IC50 3x10-9 – 1x10-9 M) [56,62]
compound 34f [PMID: 37535845] Small molecule or natural product Hs Inhibition 8.4 – 9.0 pIC50 4
⤷ pIC50 9.0 (IC50 1x10-9 M) [4]
Description: Inhibition of FLT3-D835Y catalytic activity
pIC50 8.4 (IC50 4x10-9 M) [4]
Description: Inhibition of FLT3-ITD catalytic activity
compound 2c [PMID: 24900538] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 65
⤷ pIC50 8.7 (IC50 2.1x10-9 M) [65]
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 8.5 pIC50 55
⤷ pIC50 8.5 (IC50 3x10-9 M) [55]
linifanib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 2
⤷ pIC50 8.4 (IC50 4x10-9 M) [2]
URMC-099 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 23
⤷ pIC50 8.4 (IC50 4x10-9 M) [23]
compound 18e [PMID: 31670517] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.4 pIC50 76
⤷ pIC50 8.4 (IC50 4x10-9 M) [76]
quizartinib 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 79
⤷ pIC50 8.4 (IC50 4.2x10-9 M) [79]
mivavotinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.3 pIC50 34
⤷ pIC50 8.3 (IC50 4.6x10-9 M) [34]
Description: In vitro potency
AKN-028 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.2 pIC50 16
⤷ pIC50 8.2 (IC50 6x10-9 M) [16]
sunitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pIC50 31
⤷ pIC50 8.2 (IC50 6.5x10-9 M) [31]
KW-2449 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.2 pIC50 59
⤷ pIC50 8.2 (IC50 6.6x10-9 M) [59]
sitravatinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 53
⤷ pIC50 8.1 (IC50 8x10-9 M) [53]
Description: In a biochemical enzyme activity assay.
compound 25ap [PMID: 37796543] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 pIC50 80
⤷ pIC50 8.0 (IC50 1.09x10-8 M) [80]
compound 7d [PMID: 29672049] Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 7.9 pIC50 26
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [26]
Description: In a biochemical assay.
MELK-TI Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 29
⤷ pIC50 7.7 (IC50 1.8x10-8 M) [29]
Description: Measured in a MIllipore kinase screening panel assay
tafetinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 64
⤷ pIC50 7.7 (IC50 2.08x10-8 M) [64]
Description: In a radiometric biochemical protein kinase assay.
pacritinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 70
⤷ pIC50 7.7 (IC50 2.2x10-8 M) [70]
MK-2461 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 50
⤷ pIC50 7.7 (IC50 2.2x10-8 M) [50]
JNJ-28312141 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.5 pIC50 45
⤷ pIC50 7.5 (IC50 3x10-8 M) [45]
merestinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.5 pIC50 74
⤷ pIC50 7.5 (IC50 3.1x10-8 M) [74]
Description: Inhibition of in vitro biochemical activity by EMD Millipore assay.
zotiraciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 – 7.7 pIC50 22,71
⤷ pIC50 7.3 – 7.7 (IC50 5.6x10-8 – 1.9x10-8 M) [22,71]
Flt-3 inhibitor II Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.5 pIC50 44
⤷ pIC50 7.5 (IC50 3.3x10-8 M) [44]
Flt-3 inhibitor Small molecule or natural product Primary target of this compound Hs Inhibition 7.4 pIC50 51
⤷ pIC50 7.4 (IC50 4.2x10-8 M) [51]
SGI-1776 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 pIC50 15
⤷ pIC50 7.4 (IC50 4.4x10-8 M) [15]
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 – 7.5 pIC50 69,78
⤷ pIC50 7.5 (IC50 3.3x10-8 M) [78]
pIC50 7.2 (IC50 5.8x10-8 M) [69]
Flt-3 inhibitor III Small molecule or natural product Primary target of this compound Hs Inhibition 7.3 pIC50 18
⤷ pIC50 7.3 (IC50 5x10-8 M) [18]
ruserontinib Small molecule or natural product Hs Inhibition 7.3 pIC50 8
⤷ pIC50 7.3 (IC50 5.5x10-8 M) [8]
ceritinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.2 pIC50 47
⤷ pIC50 7.2 (IC50 6x10-8 M) [47]
compound 13ac [PMID: 33256400] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pIC50 75
⤷ pIC50 7.2 (IC50 6.2x10-8 M) [75]
PF-562271 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 pIC50 57
⤷ pIC50 7.0 (IC50 9.7x10-8 M) [57]
compound 14k [PMID: 21982499] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.0 pIC50 54
⤷ pIC50 7.0 (IC50 1.04x10-7 M) [54]
BMS-690514 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.0 pIC50 46
⤷ pIC50 7.0 (IC50 1.1x10-7 M) [46]
BAY-985 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.9 pIC50 37
⤷ pIC50 6.9 (IC50 1.23x10-7 M) [37]
pexidartinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pIC50 60
⤷ pIC50 6.8 (IC50 1.6x10-7 M) [60]
edicotinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.7 pIC50 20
⤷ pIC50 6.7 (IC50 1.9x10-7 M) [20]
tandutinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.7 pIC50 30
⤷ pIC50 6.7 (IC50 2.2x10-7 M) [30]
nuvisertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.6 pIC50 17
⤷ pIC50 6.6 (IC50 2.79x10-7 M) [17]
GTP-14564 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.5 pIC50 49
⤷ pIC50 6.5 (IC50 3x10-7 M) [49]
onvansertib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 pIC50 6
⤷ pIC50 6.3 (IC50 5.1x10-7 M) [6]
AST-487 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.3 pIC50 1
⤷ pIC50 6.3 (IC50 5.2x10-7 M) [1]
midostaurin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.3 pIC50 67
⤷ pIC50 6.3 (IC50 5.28x10-7 M) [67]
cediranib Small molecule or natural product Click here for species-specific activity table Hs Inhibition <6.0 pIC50 66
⤷ pIC50 <6.0 (IC50 >1x10-6 M) [66]
compound 1 [Cruz-López et al., 2019] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 4.3 pIC50 12
⤷ pIC50 4.3 (IC50 5.35x10-5 M) [12]
Inhibitor Comments
Cyclin-dependent kinase 1 (CDK1) which shares a phenylalanine gate keeper residue in the analogous position to that in FLT3, is significantly inhibited by Flt-3 inhibitor III but with a much lower IC50 value of 2100μM [18]. c-Kit and KDR (VEGFR-2) which contain a cysteine residue at the position corresponding to Cys828 important in the binding pocket of FLT3, are also inhibited by this compound, with IC50 values of 260 and 910μM respectively [18].
G-749 inhibits FLT3 mutant D835Y with an IC50 value of 0.6nM [35].
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
LWY713 Small molecule or natural product Hs Binding - - 40
⤷ PROTAC [40]
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: 13,72
Key to terms and symbols Click column headers to sort
Target used in screen: FLT3
Ligand Sp. Type Action Value Parameter
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.4 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 9.3 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 9.2 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 9.2 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.1 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 9.1 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.1 pKd
quizartinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.9 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.5 pKd
tandutinib Small molecule or natural product Hs Inhibitor Inhibition 8.5 pKd
Target used in screen: FLT3(D835H)
Ligand Sp. Type Action Value Parameter
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.2 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.2 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.9 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 8.6 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 8.6 pKd
quizartinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 8.3 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.3 pKd
Target used in screen: FLT3(D835Y)
Ligand Sp. Type Action Value Parameter
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.4 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.2 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 8.8 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.6 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.6 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 8.3 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 8.2 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.2 pKd
Target used in screen: FLT3(ITD)
Ligand Sp. Type Action Value Parameter
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.3 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.8 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 8.7 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.6 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.6 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 8.4 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 8.4 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 8.1 pKd
Target used in screen: FLT3(K663Q)
Ligand Sp. Type Action Value Parameter
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.7 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 9.3 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.2 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 9.1 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.1 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 9.0 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 8.9 pKd
tandutinib Small molecule or natural product Hs Inhibitor Inhibition 8.8 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.7 pKd
quizartinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 pKd
Target used in screen: FLT3(N841I)
Ligand Sp. Type Action Value Parameter
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.9 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.8 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.8 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 8.6 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.6 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 8.6 pKd
quizartinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 8.3 pKd
Target used in screen: FLT3(R834Q)
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.7 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 9.1 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.4 pKd
quizartinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.3 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.1 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 8.1 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.9 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 7.8 pKd
Target used in screen: FLT3-autoinhibited
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure 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
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.9 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.7 pKd
quizartinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.2 pKd
tandutinib Small molecule or natural product Hs Inhibitor Inhibition 6.1 pKd
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 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: 3,19
Key to terms and symbols Click column headers to sort
Target used in screen: Flt3/FLT3
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.2 0.0 -1.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 0.2 24.0 3.0
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.8 1.0 -1.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.1 2.0 1.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.1 -0.5 -0.5
indirubin derivative E804 Small molecule or natural product Hs Inhibitor Inhibition 1.1 0.0 0.0
Syk inhibitor Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 1.6 1.0 -1.0
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 1.6 0.0 1.0
indirubin-3'-monoxime Small molecule or natural product Hs Inhibitor Inhibition 2.2 1.0 0.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 2.4 0.0 1.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
FLT3 is the receptor for the cytokine Flt3 ligand (FLT3LG). Flt3 ligand is a growth factor akin to stem cell factor and colony stimulating factor 1, and is essential for hematopoietic progenitor cell development and expansion of both myeloid and lymphoid lineages. It is one of the growth factor receptors targeted by the chemotherapeutic tyrosine kinase inhibitor sorafenib.
Results from mouse experiments suggest that Flt3 ligand is effective in treating sepsis, by potentiating innate immune functions of dendritic cells and neutrophils and improving T cell function [52].
Immuno Process Associations
Immuno Process:  B cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling
Immuno Process:  Antigen presentation
Immuno Process:  T cell (activation)
Immuno Disease Associations
Disease Name:  Acute myeloid leukemia
Disease Synonyms:  no synonynms
Comment:  Somatic mutations in FLT3 have been found in cases of AML Idenification of FLT3 mutations in subclones of AML patient-derived cells, suggests that these may be cooperative mutations that drive established AML clones, rather than being disease initiating mutations.
Disease X-refs:  Disease Ontology: DOID:9119
OMIM: 601626
Orphanet: ORPHA519
References:  7
Tissue Distribution Click here for help
CD34 +ve immature, multipotential, myeloid and B-lymphoid progenitor cells, and monocytic cells.
Species:  Human
Technique:  Immunocytochemistry
References:  58
Patient derived hematologic malignancy cells: from acute myelogenous leukemia (AML), B-precursor cell acute lymphoblastic leukemia (ALL), and some T-cell ALL, and chronic myelogenous leukemia (CML).
Species:  Human
Technique:  Immunocytochemistry, RT-PCR, flow-cytometry
References:  14,58
Physiological Functions Click here for help
Development of multipotent stem cells and B cells.
Species:  Mouse
Tissue:  Bone marrow, hematopoietic cells.
References:  43
Physiological Consequences of Altering Gene Expression Click here for help
Flt3 knockout mice develop normally to adulthood. They have normal mature hematopoietic populations, but have specific deficiencies in primitive B lymphoid progenitors.
Species:  Mouse
Tissue: 
Technique:  Gene-knockout
References:  43
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Acute biphenotypic leukemia
Orphanet: ORPHA98837
Disease:  Acute myeloblastic leukemia with maturation
Orphanet: ORPHA98834
Disease:  Acute myeloblastic leukemia without maturation
Orphanet: ORPHA98833
Disease:  Acute myeloid leukemia
Synonyms: Acute myelogenous leukemia
Disease Ontology: DOID:9119
OMIM: 601626
Orphanet: ORPHA519
Role:  Point mutations in the tyrosine kinase domain of FLT3 are found in 4-11% of all AML, depending on population tested. These mutations correlate with a significantly more favorable prognosis than FLT3 internal tandem duplication (FLT3-ITD) mutations.
References:  24,48
Disease:  Acute myeloid leukemia
Synonyms: Acute myelogenous leukemia
Disease Ontology: DOID:9119
OMIM: 601626
Orphanet: ORPHA519
Role:  Internal tandem duplications and/or insertions in the FLT3 gene are implicated in 20-25% of all acute myeloid leukemias and rare cases of acute lymphoblastic leukemia (ALL). Such FLT3 length mutations (FLT3-LM, a.k.a. FLT3-ITD, FLT3 internal tandem duplication) correlate with poor prognosis and a high relapse rate.
References:  33
Disease:  Acute myeloid leukemia with abnormal bone marrow eosinophils
Orphanet: ORPHA98829
Disease:  Acute myeloid leukemia with t(8;21)(q22;q22) translocation
Orphanet: ORPHA102724
Disease:  Acute myelomonocytic leukemia
Orphanet: ORPHA517
Disease:  Minimally differentiated acute myeloblastic leukemia
Orphanet: ORPHA98832
Disease:  Precursor B-cell acute lymphoblastic leukemia
Synonyms: Acute lymphocytic leukemia [Disease Ontology: DOID:9952]
Leukemia, acute lymphoblastic; ALL [OMIM: 613065]
Leukemia, B-cell acute lymphoblastic, susceptibility to [OMIM: 613065]
Disease Ontology: DOID:9952
OMIM: 613065
Orphanet: ORPHA99860
Disease:  Precursor T-cell acute lymphoblastic leukemia
Synonyms: Acute lymphocytic leukemia [Disease Ontology: DOID:9952]
Leukemia, acute lymphoblastic; ALL [OMIM: 613065]
Leukemia, T-cell acute lymphoblastic, susceptibility to [OMIM: 613065]
Disease Ontology: DOID:9952
OMIM: 613065
Orphanet: ORPHA99861

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Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family: fms related receptor tyrosine kinase 3. Last modified on 06/03/2024. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1807.