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KIT proto-oncogene, receptor tyrosine kinase

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 1805

Nomenclature: KIT proto-oncogene, receptor tyrosine kinase

Abbreviated Name: Kit

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 1 976 4q12 KIT KIT proto-oncogene, receptor tyrosine kinase
Mouse 1 979 5 39.55 cM Kit KIT proto-oncogene receptor tyrosine kinase
Rat - 978 14p11 Kit KIT proto-oncogene receptor tyrosine kinase
Previous and Unofficial Names Click here for help
CD117 | C-Kit | PBT | stem cell growth factor receptor | piebald trait | c-kit receptor tyrosine kinase | mast/stem cell growth factor receptor | p145 c-kit | Proto-oncogene c-Kit | Steel Factor Receptor | v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog | kit oncogene | KIT proto-oncogene receptor tyrosine kinase
Database Links Click here for help
Alphafold P10721 (Hs), P05532 (Mm)
BRENDA 2.7.10.1
CATH/Gene3D 2.60.40.10
ChEMBL Target CHEMBL1936 (Hs), CHEMBL2034798 (Mm)
DrugBank Target P10721 (Hs)
Ensembl Gene ENSG00000157404 (Hs), ENSMUSG00000005672 (Mm), ENSRNOG00000002227 (Rn)
Entrez Gene 3815 (Hs), 16590 (Mm), 64030 (Rn)
Human Protein Atlas ENSG00000157404 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:3815 (Hs), mmu:16590 (Mm), rno:64030 (Rn)
OMIM 164920 (Hs)
Orphanet ORPHA122862 (Hs)
Pharos P10721 (Hs)
RefSeq Nucleotide NM_000222 (Hs), NM_001122733 (Mm), NM_022264 (Rn)
RefSeq Protein NP_000213 (Hs), NP_066922 (Mm), NP_001116205 (Mm), NP_071600 (Rn)
SynPHARM 81286 (in complex with sunitinib)
81225 (in complex with sunitinib)
UniProtKB P10721 (Hs), P05532 (Mm)
Wikipedia KIT (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the extracellular domain of the receptor tyrosine kinase, Kit
PDB Id:  2EC8
Resolution:  3.0Å
Species:  Human
References:  68
Image of receptor 3D structure from RCSB PDB
Description:  KIT kinase domain in complex with sunitinib
PDB Id:  3G0E
Ligand:  sunitinib
Resolution:  1.6Å
Species:  Human
References:  18
Enzyme Reaction Click here for help
EC Number: 2.7.10.1
Natural/Endogenous Ligands Click here for help
stem cell factor {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
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 9.4 pKd 12
⤷ pKd 9.4 (Kd 3.7x10-10 M) [12]
AC710 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.0 pKd 40
⤷ pKd 9.0 (Kd 1x10-9 M) [40]
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 2.6x10-9 M) [9]
quizartinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.3 pKd 10
⤷ pKd 8.3 (Kd 4.8x10-9 M) [10]
masitinib 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 12
⤷ pKd 8.1 (Kd 8.1x10-9 M) [12]
RG-1530 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pKd 58
⤷ pKd 7.6 (Kd 2.6x10-8 M) [58]
crenolanib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.1 pKd 30
⤷ pKd 7.1 (Kd 7.8x10-8 M) [30]
BPR1R024 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.0 pIC50 38
⤷ pIC50 9.0 (IC50 1.1x10-9 M) [38]
famitinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.7 pIC50 11
⤷ pIC50 8.7 (IC50 2x10-9 M) [11]
dovitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 – 8.7 pIC50 51,59
⤷ pIC50 8.5 – 8.7 (IC50 3x10-9 – 2x10-9 M) [51,59]
cediranib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.5 pIC50 61
⤷ pIC50 8.5 (IC50 3x10-9 M) [61]
CHMFL-KIT-64 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 65
⤷ pIC50 8.4 (IC50 4x10-9 M) [65]
Description: In a biochemical assay.
ibcasertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 71
⤷ pIC50 8.4 (IC50 4x10-9 M) [71]
Description: Inhibition in a biochemical assay.
elenestinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition >8.4 pIC50 35
⤷ pIC50 >8.4 (IC50 <4.5x10-9 M) [35]
Description: Biochemical inhibition assay, using KITD816V
compound 7k [PMID: 23521020] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pIC50 20
⤷ pIC50 8.3 (IC50 4.89x10-9 M) [20]
JNJ-28312141 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pIC50 42
⤷ pIC50 8.3 (IC50 5x10-9 M) [42]
sitravatinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.2 pIC50 48
⤷ pIC50 8.2 (IC50 6x10-9 M) [48]
Description: In a biochemical enzyme activity assay.
risvodetinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 62
⤷ pIC50 8.1 (IC50 7.8x10-9 M) [62]
henatinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 11
⤷ pIC50 8.1 (IC50 8x10-9 M) [11]
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 8.0 pIC50 16
⤷ pIC50 8.0 (IC50 1x10-8 M) [16]
KBP-7018 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.0 pIC50 31
⤷ pIC50 8.0 (IC50 1x10-8 M) [31]
compound 8h [PMID: 22765894] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 pIC50 36
⤷ pIC50 8.0 (IC50 1.1x10-8 M) [36]
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 7.9 pIC50 34
⤷ pIC50 7.9 (IC50 1.31x10-8 M) [34]
compound 8i [PMID: 22765894] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pIC50 67
⤷ pIC50 7.9 (IC50 1.38x10-8 M) [67]
linifanib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.8 pIC50 3
⤷ pIC50 7.8 (IC50 1.4x10-8 M) [3]
SU-14813 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.8 pIC50 49
⤷ pIC50 7.8 (IC50 1.5x10-8 M) [49]
edicotinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.7 pIC50 24
⤷ pIC50 7.7 (IC50 2x10-8 M) [24]
ilorasertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 25
⤷ pIC50 7.7 (IC50 2x10-8 M) [25]
Description: Measuring inhibition of kinase activity in a biochemical assay.
labuxtinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 7.7 pIC50 66
⤷ pIC50 7.7 (IC50 2x10-8 M) [66]
pexidartinib 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 >7.6 pIC50 55
⤷ pIC50 >7.6 (IC50 <2.7x10-8 M) [55]
bezuclastinib Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.6 pIC50 23
⤷ pIC50 7.6 (IC50 2.8x10-8 M) [23]
Description: Inhibition of KITV560G/D816V
AKN-028 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.5 pIC50 14
⤷ pIC50 7.5 (IC50 2.9x10-8 M) [14]
Description: Inhibition of KIT autophosphorylation in human AML M07 cells which overexpress KIT
CHMFL-KIT-8140 Small molecule or natural product Hs Inhibition 7.5 pIC50 39
⤷ pIC50 7.5 (IC50 3.3x10-8 M) [39]
M4205 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pIC50 7
⤷ pIC50 7.4 (IC50 4.4x10-8 M) [7]
compound 19a [PMID: 30503936] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pIC50 50
⤷ pIC50 7.2 (IC50 6.4x10-8 M) [50]
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 pIC50 63,67
⤷ pIC50 7.2 (IC50 6.8x10-8 M) [67]
pIC50 7.2 (IC50 6.8x10-8 M) [63]
avapritinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.1 pIC50 15
⤷ pIC50 7.1 (IC50 7.3x10-8 M) [15]
PLX5622 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition <7.0 pIC50 69
⤷ pIC50 <7.0 (IC50 >1x10-7 M) [69]
Description: Binned IC50 value from patent data
OSI-930 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 – 7.6 pIC50 22
⤷ pIC50 6.4 – 7.6 (IC50 4x10-7 – 2.5x10-8 M) [22]
Description: The IC50 varied dependent on whether KIT was activated or unactivated, with the lower value measured for the activated enzyme.
pazopanib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 6.8 pIC50 29
⤷ pIC50 6.8 (IC50 1.4x10-7 M) [29]
tandutinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pIC50 33
⤷ pIC50 6.8 (IC50 1.7x10-7 M) [33]
masitinib 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 6.7 pIC50 13
⤷ pIC50 6.7 (IC50 2x10-7 M) [13]
CP-673451 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 pIC50 52
⤷ pIC50 6.6 (IC50 2.52x10-7 M) [52]
GTP-14564 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.5 pIC50 44
⤷ pIC50 6.5 (IC50 3x10-7 M) [44]
vimseltinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.0 – 7.0 pIC50 1
⤷ pIC50 6.0 – 7.0 (IC50 1x10-6 – 1x10-7 M) [1]
semaxanib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.4 pIC50 8
⤷ pIC50 6.4 (IC50 4x10-7 M) [8]
rivoceranib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 6.4 pIC50 57
⤷ pIC50 6.4 (IC50 4.29x10-7 M) [57]
Description: Assay used apatinib mesylate (YN968D1)
Ki-20227 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 pIC50 45
⤷ pIC50 6.3 (IC50 4.51x10-7 M) [45]
AST-487 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 pIC50 2
⤷ pIC50 6.3 (IC50 5x10-7 M) [2]
Description: In vitro inhibition of c-Kit
lucitanib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 pIC50 70
⤷ pIC50 6.3 (IC50 5.27x10-7 M) [70]
flumbatinib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 6.2 pIC50 41
⤷ pIC50 6.2 (IC50 6.66x10-7 M) [41]
sotuletinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.4 pIC50 54
⤷ pIC50 5.4 (IC50 3.88x10-6 M) [54]
ripretinib Small molecule or natural product Approved drug Hs Inhibition - - 17
⤷ [17]
Inhibitor Comments
Note that the primary target of avapritinib (BLU-285) is mutant, constitutively active KIT rather than the wild type kinase [15].
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
stem cell factor {Sp: Human} Peptide Ligand is endogenous in the given species Immunopharmacology Ligand Hs Agonist 9.6 – 9.8 pKd 60
⤷ pKd 9.6 – 9.8 (Kd 2.4x10-10 – 1.5x10-10 M) [60]
Description: Binding affinity of KIT receptors on cell membranes from OCIM1, MO7e and HEL cells, using 125I-SCF as radioligand.
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
barzolvolimab Peptide Hs Binding - - 28
⤷ [28]
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: 12,64
Key to terms and symbols Click column headers to sort
Target used in screen: KIT
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
cediranib Small molecule or natural product Hs Inhibitor Inhibition 9.4 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 9.2 pKd
Ki-20227 Small molecule or natural product Hs Inhibitor Inhibition 9.2 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.1 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 8.7 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.6 pKd
tandutinib Small molecule or natural product Hs Inhibitor Inhibition 8.6 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 8.6 pKd
Target used in screen: KIT(A829P)
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.2 pKd
dasatinib Small molecule or natural product Approved drug 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 8.5 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.5 pKd
quizartinib 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 8.4 pKd
masitinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.9 pKd
motesanib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
imatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.8 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 7.8 pKd
Target used in screen: KIT(D816H)
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.4 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.8 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.2 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.0 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.8 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 7.3 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 7.2 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
tandutinib Small molecule or natural product Hs Inhibitor Inhibition 6.9 pKd
Target used in screen: KIT(D816V)
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.2 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.6 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.6 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.1 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.1 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 7.7 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.6 pKd
tandutinib Small molecule or natural product Hs Inhibitor Inhibition 7.5 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.5 pKd
Target used in screen: KIT(L576P)
Ligand Sp. Type Action Value Parameter
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 9.5 pKd
cediranib Small molecule or natural product Hs Inhibitor Inhibition 9.3 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.2 pKd
Ki-20227 Small molecule or natural product Hs Inhibitor Inhibition 9.1 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.9 pKd
motesanib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.9 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 8.8 pKd
axitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.8 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 8.7 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 8.7 pKd
Target used in screen: KIT(V559D)
Ligand Sp. Type Action Value Parameter
cediranib Small molecule or natural product Hs Inhibitor Inhibition 9.6 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.4 pKd
Ki-20227 Small molecule or natural product Hs Inhibitor Inhibition 9.3 pKd
axitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.3 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 9.3 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.2 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.8 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 8.8 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 8.6 pKd
Target used in screen: KIT(V559D,T670I)
Ligand Sp. Type Action Value Parameter
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.6 pKd
cediranib Small molecule or natural product Hs Inhibitor Inhibition 9.5 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 9.3 pKd
axitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.9 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.6 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 8.4 pKd
quizartinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.2 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 8.2 pKd
barasertib-hQPA Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
Target used in screen: KIT(V559D,V654A)
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
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 9.6 pKd
cediranib Small molecule or natural product Hs Inhibitor Inhibition 9.5 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.6 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 8.5 pKd
Ki-20227 Small molecule or natural product Hs Inhibitor Inhibition 8.5 pKd
axitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.5 pKd
masitinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.3 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 8.2 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
Target used in screen: KIT-autoinhibited
Ligand Sp. Type Action Value Parameter
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.9 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.5 pKd
Ki-20227 Small molecule or natural product Hs Inhibitor Inhibition 7.3 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
quizartinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 5.9 pKd
vatalanib Small molecule or natural product Hs Inhibitor Inhibition 5.8 pKd
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 5.7 pKd
imatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.3 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: 4,21
Key to terms and symbols Click column headers to sort
Target used in screen: cKit/c-Kit
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 3.3
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.7
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 9.5 1.0
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 9.9
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 10.9
Flt-3 inhibitor III Small molecule or natural product Hs Inhibitor Inhibition 20.3 1.0 1.0
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 21.4 5.0 2.0
Lck inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 21.6 36.0 1.0
PDK1/Akt/Flt dual pathway inhibitor Small molecule or natural product Hs Inhibitor Inhibition 22.2 114.0 96.0
PDGF receptor tyrosine kinase inhibitor IV Small molecule or natural product Hs Inhibitor Inhibition 27.9 0.0 0.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
Stem cell factor (SCF) and its receptor KIT (c-KIT) play an essential part in mast cell biology. In addition to CSF/KIT-mediated regulation of mast cell development, proliferation and survival, KIT is also reported to be involved in the adhesion of mast cells to human airway epithelial cells (a homing and adhesion role), suggesting a mechanism that could be targeted for anti-asthmatic potential [26]. In addition, SCF is considered necessary for optimal IgE/antigen-induced mast cell degranulation and cytokine production. A study in mice suggests KIT my play a role in regulating type 2 innate lymphoid cell accumulation and central nervous system demyelination (providing a potential link with multiple sclerosis, and an explanation for MS disproportionately affecting women) [53]. Experimental bispecific antibodies crosslinking KIT with inhibitory CD300a inhibit human mast cell differentiation and CBMC survival and activation [5]. Additional strategies targeting the KIT pathway in allergic inflammatory disease are reviewed in [32].
Cell Type Associations
Immuno Cell Type:  Mast cells
Cell Ontology Term:   mast cell (CL:0000097)
Comment:  Mast cells ubiquitously express KIT. It is expressed by mast cell precursors and mature mast cells.
References:  19
Immuno Process Associations
Immuno Process:  Barrier integrity
Immuno Process:  Inflammation
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
Immuno Disease Associations
Disease Name:  Mastocytosis
Disease Synonyms:  no synonynms
Comment:  Constitutively active KIT D816V is associated with mast cell clonal disorders. KIT D816V detection in blood and bone marrow is important for diagnosing systemic mastocytosis.
Disease X-refs:  Disease Ontology: DOID:350
References:  6,27,46,56
Disease Name:  Acute myeloid leukemia
Disease Synonyms:  no synonynms
Comment:  KIT mutations have been identified in founding clones from AML patients, which suggests that KIT mutations initiate development of AML.
Disease X-refs:  Disease Ontology: DOID:9119
OMIM: 601626
Orphanet: ORPHA519
References:  43
Physiological Functions Click here for help
KIT regulates mast cell growth, survival, chemotaxis and degranulation.
Species:  Human
Tissue: 
References:  47
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Acute myeloblastic leukemia with maturation
Orphanet: ORPHA98834
Disease:  Acute myeloid leukemia
Synonyms: Acute myelogenous leukemia
Disease Ontology: DOID:9119
OMIM: 601626
Orphanet: ORPHA519
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:  Aleukemic mast cell leukemia
Orphanet: ORPHA158799
Disease:  Bullous diffuse cutaneous mastocytosis
Orphanet: ORPHA280785
Disease:  Classic mast cell leukemia
Orphanet: ORPHA158796
Disease:  Cutaneous mastocytoma
Orphanet: ORPHA79455
Disease:  Gastrointestinal stromal tumor
Disease Ontology: DOID:9253
OMIM: 606764
Orphanet: ORPHA44890
Comments:  A heterozygous mutation in KIT is implicated in the familial form of gastrointestinal tumors
Disease:  Isolated bone marrow mastocytosis
Orphanet: ORPHA158778
Disease:  Lymphoadenopathic mastocytosis with eosinophilia
Orphanet: ORPHA158793
Disease:  Mast cell disease
Synonyms: Maculopapular cutaneous mastocytosis [Orphanet: ORPHA79457]
Typical urticaria pigmentosa [Orphanet: ORPHA158766]
Urticaria pigmentosa [Disease Ontology: DOID:12309]
Disease Ontology: DOID:12309
OMIM: 154800
Orphanet: ORPHA79457, ORPHA158766
Disease:  Mastocytosis
Description: A disease caused by mast cell hyperplasia.
Disease Ontology: DOID:350
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human D816V Constitutively active KIT D816V is associated with mast cell clonal disorders. KIT D816V detection in blood and bone marrow is important for diagnosing systemic mastocytosis. 6,46,56
Disease:  Mastocytosis
Description: A disease caused by mast cell hyperplasia.
Disease Ontology: DOID:350
Role:  Gain-of-function somatic point mutations of the c-Kit gene (e.g. KITD816V mutation) are known to drive adult-onset mastocytosis. A small number of pediatric mastocytosis cases have been linked to elevated KIT activity.
Comments:  KIT-blocking agents are being investigated as modulators of mast cell-related diseases including chronic idiopathic urticaria.
References:  37,47
Disease:  Nodular urticaria pigmentosa
Orphanet: ORPHA158772
Disease:  Piebaldism
Synonyms: Piebald trait [OMIM: 172800]
Disease Ontology: DOID:3263
OMIM: 172800
Orphanet: ORPHA2884
Disease:  Plaque-form urticaria pigmentosa
Orphanet: ORPHA158769
Disease:  Pseudoxanthomatous diffuse cutaneous mastocytosis
Orphanet: ORPHA280794
Disease:  Smouldering systemic mastocytosis
Orphanet: ORPHA158775
Disease:  Systemic mastocytosis with an associated clonal hematologic non-mast cell lineage disease
Orphanet: ORPHA98849
Disease:  Telangiectasia macularis eruptiva perstans
Orphanet: ORPHA90389
Disease:  Testicular germ cell tumor
Synonyms: Seminoma [Disease Ontology: DOID:4440]
Testicular pure germ cell tumor [Disease Ontology: DOID:4087]
Disease Ontology: DOID:4440, DOID:4087
OMIM: 273300

References

Show »

1. Ahn Y,Vogeti L, Caldwell TM, Kaufman MD, Flynn DL. (2014) 2-aminopyrimidin-6-ones and analogs exhibiting anti-cancer and anti-proliferative activities. Patent number: WO2014145025A2. Assignee: Deciphera Pharmaceuticals, Llc. Priority date: 15/03/2013. Publication date: 18/09/2014.

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. Bachelet I, Munitz A, Berent-Maoz B, Mankuta D, Levi-Schaffer F. (2008) Suppression of normal and malignant kit signaling by a bispecific antibody linking kit with CD300a. J Immunol, 180 (9): 6064-9. [PMID:18424727]

6. Bibi S, Zhang Y, Hugonin C, Mangean MD, He L, Wedeh G, Launay JM, Van Rijn S, Würdinger T, Louache F et al.. (2016) A new humanized in vivo model of KIT D816V+ advanced systemic mastocytosis monitored using a secreted luciferase. Oncotarget, 7 (50): 82985-83000. [PMID:27783996]

7. Blum A, Dorsch D, Linde N, Brandstetter S, Buchstaller HP, Busch M, Glaser N, Grädler U, Ruff A, Petersson C et al.. (2023) Identification of M4205─A Highly Selective Inhibitor of KIT Mutations for Treatment of Unresectable Metastatic or Recurrent Gastrointestinal Stromal Tumors. J Med Chem, 66 (4): 2386-2395. [PMID:36728508]

8. 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]

9. Chan S, Zhang Y, Wang J, Yu Q, Peng X, Zou J, Zhou L, Tan L, Duan Y, Zhou Y et al.. (2022) Discovery of 3-Aminopyrazole Derivatives as New Potent and Orally Bioavailable AXL Inhibitors. Journal of Nedicinal Chemistry,. DOI: 10.1021/acs.jmedchem.2c01346

10. Chao Q, Sprankle KG, Grotzfeld RM, Lai AG, Carter TA, Velasco AM, Gunawardane RN, Cramer MD, Gardner MF, James J et al.. (2009) Identification of N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea dihydrochloride (AC220), a uniquely potent, selective, and efficacious FMS-like tyrosine kinase-3 (FLT3) inhibitor. J Med Chem, 52 (23): 7808-16. [PMID:19754199]

11. 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]

12. 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]

13. Dubreuil P, Letard S, Ciufolini M, Gros L, Humbert M, Castéran N, Borge L, Hajem B, Lermet A, Sippl W et al.. (2009) Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS ONE, 4 (9): e7258. [PMID:19789626]

14. Eriksson A, Hermanson M, Wickström M, Lindhagen E, Ekholm C, Jenmalm Jensen A, Löthgren A, Lehmann F, Larsson R, Parrow V et al.. (2012) The novel tyrosine kinase inhibitor AKN-028 has significant antileukemic activity in cell lines and primary cultures of acute myeloid leukemia. Blood Cancer J, 2: e81. [PMID:22864397]

15. Evans EK, Gardino AK, Kim JL, Hodous BL, Shutes A, Davis A, Zhu XJ, Schmidt-Kittler O, Wilson D, Wilson K et al.. (2017) A precision therapy against cancers driven by KIT/PDGFRA mutations. Sci Transl Med, 9 (414). [PMID:29093181]

16. 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]

17. Flynn DL, Petillo PA, Kaufman MD. (2010) Cyclopropane amides and analogs exhibiting anti-cancer and anti-proliferative activities. Patent number: WO2010051373. Assignee: Deciphera Pharmaceuticals, Llc. Priority date: 29/10/2008. Publication date: 06/05/2010.

18. Gajiwala KS, Wu JC, Christensen J, Deshmukh GD, Diehl W, DiNitto JP, English JM, Greig MJ, He YA, Jacques SL et al.. (2009) KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Proc Natl Acad Sci USA, 106 (5): 1542-7. [PMID:19164557]

19. Gangwar RS, Landolina N, Arpinati L, Levi-Schaffer F. (2017) Mast cell and eosinophil surface receptors as targets for anti-allergic therapy. Pharmacol Ther, 170: 37-63. [PMID:27773785]

20. Gao M, Duan L, Luo J, Zhang L, Lu X, Zhang Y, Zhang Z, Tu Z, Xu Y, Ren X et al.. (2013) Discovery and optimization of 3-(2-(Pyrazolo[1,5-a]pyrimidin-6-yl)ethynyl)benzamides as novel selective and orally bioavailable discoidin domain receptor 1 (DDR1) inhibitors. J Med Chem, 56 (8): 3281-95. [PMID:23521020]

21. 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]

22. 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]

23. Gebreyohannes YK, Burton EA, Wozniak A, Matusow B, Habets G, Wellens J, Cornillie J, Lin J, Nespi M, Wu G et al.. (2019) PLX9486 shows anti-tumor efficacy in patient-derived, tyrosine kinase inhibitor-resistant KIT-mutant xenograft models of gastrointestinal stromal tumors. Clin Exp Med, 19 (2): 201-210. [PMID:30523507]

24. Genovese MC, Hsia E, Belkowski SM, Chien C, Masterson T, Thurmond RL, Manthey CL, Yan XD, Ge T, Franks C et al.. (2015) Results from a Phase IIA Parallel Group Study of JNJ-40346527, an Oral CSF-1R Inhibitor, in Patients with Active Rheumatoid Arthritis despite Disease-modifying Antirheumatic Drug Therapy. J Rheumatol, 42 (10): 1752-60. [PMID:26233509]

25. 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]

26. Gough KC, Maddison BC, Shikotra A, Moiseeva EP, Yang W, Jarvis S, Bradding P. (2015) Evidence for a novel Kit adhesion domain mediating human mast cell adhesion to structural airway cells. Respir Res, 16: 86. [PMID:26173671]

27. Greiner G, Gurbisz M, Ratzinger F, Witzeneder N, Simonitsch-Klupp I, Mitterbauer-Hohendanner G, Mayerhofer M, Müllauer L, Sperr WR, Valent P et al.. (2018) Digital PCR: A Sensitive and Precise Method forKITD816V Quantification in Mastocytosis. Clin Chem, 64 (3): 547-555. [PMID:29237714]

28. Hadari Y, Mandel-Bausch EM Carr FJ, Jones TD, Perry LCA. (2020) Anti-kit antibodies and uses thereof. Patent number: US10781267B2. Assignee: Celldex Therapeutics Inc. Priority date: 25/07/2012. Publication date: 22/09/2020.

29. 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]

30. Heinrich MC, Griffith D, McKinley A, Patterson J, Presnell A, Ramachandran A, Debiec-Rychter M. (2012) Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin Cancer Res, 18 (16): 4375-84. [PMID:22745105]

31. Huang Z, Li H, Zhang Q, Lu F, Hong M, Zhang Z, Guo X, Zhu Y, Li S, Liu H. (2017) Discovery of Indolinone-Based Multikinase Inhibitors as Potential Therapeutics for Idiopathic Pulmonary Fibrosis. ACS Med Chem Lett, 8 (11): 1142-1147. [PMID:29152045]

32. Jensen BM, Metcalfe DD, Gilfillan AM. (2007) Targeting kit activation: a potential therapeutic approach in the treatment of allergic inflammation. Inflamm Allergy Drug Targets, 6 (1): 57-62. [PMID:17352689]

33. Kelly LM, Yu JC, Boulton CL, Apatira M, Li J, Sullivan CM, Williams I, Amaral SM, Curley DP, Duclos N et al.. (2002) CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell, 1 (5): 421-32. [PMID:12124172]

34. 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]

35. Kim JL, Dineen TA, Guzi T. (2020) Pyrrolotriazine derivatives for treating kit- and pdgfra-mediated diseases. Patent number: WO2020210293A1. Assignee: Blueprint Medicines Corporation. Priority date: 08/04/2020. Publication date: 15/10/2020.

36. 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]

37. Kristensen T, Vestergaard H, Bindslev-Jensen C, Mortz CG, Kjaer HF, Ollert M, Møller MB, Broesby-Olsen S, Mastocytosis Centre Odense University Hospital (MastOUH). (2017) Prospective evaluation of the diagnostic value of sensitive KIT D816V mutation analysis of blood in adults with suspected systemic mastocytosis. Allergy, 72 (11): 1737-1743. [PMID:28432683]

38. Lee KH, Yen WC, Lin WH, Wang PC, Lai YL, Su YC, Chang CY, Wu CS, Huang YC, Yang CM et al.. (2021) Discovery of BPR1R024, an Orally Active and Selective CSF1R Inhibitor that Exhibits Antitumor and Immunomodulatory Activity in a Murine Colon Tumor Model. J Med Chem, 64 (19): 14477-14497. [PMID:34606263]

39. Li B, Wang A, Liu J, Qi Z, Liu X, Yu K, Wu H, Chen C, Hu C, Wang W et al.. (2016) Discovery of N-((1-(4-(3-(3-((6,7-Dimethoxyquinolin-3-yl)oxy)phenyl)ureido)-2-(trifluoromethyl)phenyl)piperidin-4-yl)methyl)propionamide (CHMFL-KIT-8140) as a Highly Potent Type II Inhibitor Capable of Inhibiting the T670I "Gatekeeper" Mutant of cKIT Kinase. J Med Chem, 59 (18): 8456-72. [PMID:27545040]

40. Liu G, Campbell BT, Holladay MW, Ford Pulido JM, Hua H, Gitnick D, Gardner MF, James J, Breider MA, Brigham D et al.. (2012) Discovery of AC710, a Globally Selective Inhibitor of Platelet-Derived Growth Factor Receptor-Family Kinases. ACS Med Chem Lett, 3 (12): 997-1002. [PMID:24900421]

41. Luo H, Quan H, Xie C, Xu Y, Fu L, Lou L. (2010) HH-GV-678, a novel selective inhibitor of Bcr-Abl, outperforms imatinib and effectively overrides imatinib resistance. Leukemia, 24 (10): 1807-9. [PMID:20703259]

42. Manthey CL, Johnson DL, Illig CR, Tuman RW, Zhou Z, Baker JF, Chaikin MA, Donatelli RR, Franks CF, Zeng L et al.. (2009) JNJ-28312141, a novel orally active colony-stimulating factor-1 receptor/FMS-related receptor tyrosine kinase-3 receptor tyrosine kinase inhibitor with potential utility in solid tumors, bone metastases, and acute myeloid leukemia. Mol Cancer Ther, 8 (11): 3151-61. [PMID:19887542]

43. Miller CA, Wilson RK, Ley TJ. (2013) Genomic landscapes and clonality of de novo AML. N Engl J Med, 369 (15): 1473. [PMID:24106950]

44. Murata K, Kumagai H, Kawashima T, Tamitsu K, Irie M, Nakajima H, Suzu S, Shibuya M, Kamihira S, Nosaka T et al.. (2003) Selective cytotoxic mechanism of GTP-14564, a novel tyrosine kinase inhibitor in leukemia cells expressing a constitutively active Fms-like tyrosine kinase 3 (FLT3). J Biol Chem, 278 (35): 32892-8. [PMID:12815052]

45. 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]

46. Onnes MC, Tanno LK, Elberink JN. (2016) Mast Cell Clonal Disorders: Classification, Diagnosis and Management. Curr Treat Options Allergy, 3 (4): 453-464. [PMID:27942432]

47. Pardanani A. (2019) Systemic mastocytosis in adults: 2019 update on diagnosis, risk stratification and management. Am J Hematol, 94 (3): 363-377. [PMID:30536695]

48. 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]

49. 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]

50. 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]

51. 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]

52. Roberts WG, Whalen PM, Soderstrom E, Moraski G, Lyssikatos JP, Wang HF, Cooper B, Baker DA, Savage D, Dalvie D et al.. (2005) Antiangiogenic and antitumor activity of a selective PDGFR tyrosine kinase inhibitor, CP-673,451. Cancer Res, 65 (3): 957-66. [PMID:15705896]

53. Russi AE, Walker-Caulfield ME, Ebel ME, Brown MA. (2015) Cutting edge: c-Kit signaling differentially regulates type 2 innate lymphoid cell accumulation and susceptibility to central nervous system demyelination in male and female SJL mice. J Immunol, 194 (12): 5609-13. [PMID:25972476]

54. Strachan DC, Ruffell B, Oei Y, Bissell MJ, Coussens LM, Pryer N, Daniel D. (2013) CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8(+) T cells. Oncoimmunology, 2 (12): e26968. [PMID:24498562]

55. 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]

56. Taylor ML, Sehgal D, Raffeld M, Obiakor H, Akin C, Mage RG, Metcalfe DD. (2004) Demonstration that mast cells, T cells, and B cells bearing the activating kit mutation D816V occur in clusters within the marrow of patients with mastocytosis. J Mol Diagn, 6 (4): 335-42. [PMID:15507672]

57. 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]

58. 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]

59. 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]

60. Turner AM, Bennett LG, Lin NL, Wypych J, Bartley TD, Hunt RW, Atkins HL, Langley KE, Parker V, Martin F et al.. (1995) Identification and characterization of a soluble c-kit receptor produced by human hematopoietic cell lines. Blood, 85 (8): 2052-8. [PMID:7536489]

61. 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]

62. Werner MH, Kelly TA. (2020) Compositions and methods for inhibiting kinases. Patent number: US20200046699A1. Assignee: Inhibikase Therapeutics Inc. Priority date: 25/10/2017. Publication date: 13/02/2020.

63. 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]

64. 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]

65. Wu Y, Wang B, Wang J, Qi S, Zou F, Qi Z, Liu F, Liu Q, Chen C, Hu C et al.. (2019) Discovery of 2-(4-Chloro-3-(trifluoromethyl)phenyl)-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)acetamide (CHMFL-KIT-64) as a Novel Orally Available Potent Inhibitor against Broad-Spectrum Mutants of c-KIT Kinase for Gastrointestinal Stromal Tumors. J Med Chem, 62 (13): 6083-6101. [PMID:31250638]

66. Yeh V, Li X, Liu X, Loren J, Molteni V, Nabakka J, Nguyen B, Michael H, Petrassi J. (2013) COMPOUNDS AND COMPOSITIONS AS c-KIT KINASE INHIBITORS. Patent number: WO2013033070A1. Assignee: Irm Llc. Priority date: 28/08/2012. Publication date: 07/03/2013.

67. 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]

68. Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J. (2007) Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor. Cell, 130 (2): 323-34. [PMID:17662946]

69. Zhang J, Ibrahim PN, Bremer R, Spevak W, Cho H. (2015) Compounds and methods for kinase modulation, and indications therefor. Patent number: US9096593B2. Assignee: Plexxikon Inc. Priority date: 20/09/2013. Publication date: 08/04/2015.

70. 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]

71. 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]

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Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family: KIT proto-oncogene, receptor tyrosine kinase. Last modified on 11/08/2023. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1805.