KIT proto-oncogene, receptor tyrosine kinase | Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family | IUPHAR/BPS Guide to PHARMACOLOGY

Top ▲

KIT proto-oncogene, receptor tyrosine kinase

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

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

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 976 4q11-q12 KIT KIT proto-oncogene, receptor tyrosine kinase
Mouse 1 979 5 Kit KIT proto-oncogene receptor tyrosine kinase
Rat - 978 14p11 Kit KIT proto-oncogene receptor tyrosine kinase
Previous and Unofficial Names
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
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the extracellular domain of the receptor tyrosine kinase, Kit
PDB Id:  2EC8
Resolution:  3.0Å
Species:  Human
References:  56
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:  15
Enzyme Reaction
EC Number: 2.7.10.1
Natural/Endogenous Ligands
stem cell factor {Sp: Human}

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

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
sunitinib Hs Inhibition 9.4 pKd 9
pKd 9.4 (Kd 3.7x10-10 M) [9]
AC710 Hs Inhibition 9.0 pKd 32
pKd 9.0 (Kd 1x10-9 M) [32]
quizartinib Hs Inhibition 8.3 pKd 7
pKd 8.3 (Kd 4.8x10-9 M) [7]
masitinib Hs Inhibition 8.1 pKd 9
pKd 8.1 (Kd 8.1x10-9 M) [9]
RG-1530 Hs Inhibition 7.6 pKd 49
pKd 7.6 (Kd 2.6x10-8 M) [49]
crenolanib Hs Inhibition 7.1 pKd 25
pKd 7.1 (Kd 7.8x10-8 M) [25]
famitinib Hs Inhibition 8.7 pIC50 8
pIC50 8.7 (IC50 2x10-9 M) [8]
dovitinib Hs Inhibition 8.5 – 8.7 pIC50 42,50
pIC50 8.5 – 8.7 (IC50 3x10-9 – 2x10-9 M) [42,50]
cediranib Hs Inhibition 8.5 pIC50 52
pIC50 8.5 (IC50 3x10-9 M) [52]
compound 7k [PMID: 23521020] Hs Inhibition 8.3 pIC50 17
pIC50 8.3 (IC50 4.89x10-9 M) [17]
JNJ-28312141 Hs Inhibition 8.3 pIC50 34
pIC50 8.3 (IC50 5x10-9 M) [34]
sitravatinib Hs Inhibition 8.2 pIC50 39
pIC50 8.2 (IC50 6x10-9 M) [39]
Description: In a biochemical enzyme activity assay.
henatinib Hs Inhibition 8.1 pIC50 8
pIC50 8.1 (IC50 8x10-9 M) [8]
SU11652 Hs Inhibition 8.0 pIC50 13
pIC50 8.0 (IC50 1x10-8 M) [13]
KBP-7018 Hs Inhibition 8.0 pIC50 26
pIC50 8.0 (IC50 1x10-8 M) [26]
compound 8h [PMID: 22765894] Hs Inhibition 8.0 pIC50 30
pIC50 8.0 (IC50 1.1x10-8 M) [30]
sunitinib Hs Inhibition 7.9 pIC50 29
pIC50 7.9 (IC50 1.31x10-8 M) [29]
compound 8i [PMID: 22765894] Hs Inhibition 7.9 pIC50 55
pIC50 7.9 (IC50 1.38x10-8 M) [55]
linifanib Hs Inhibition 7.8 pIC50 2
pIC50 7.8 (IC50 1.4x10-8 M) [2]
SU-14813 Hs Inhibition 7.8 pIC50 40
pIC50 7.8 (IC50 1.5x10-8 M) [40]
edicotinib Hs Inhibition 7.7 pIC50 20
pIC50 7.7 (IC50 2x10-8 M) [20]
ilorasertib Hs Inhibition 7.7 pIC50 21
pIC50 7.7 (IC50 2x10-8 M) [21]
Description: Measuring inhibition of kinase activity in a biochemical assay.
pexidartinib Hs Inhibition >7.6 pIC50 46
pIC50 >7.6 (IC50 <2.7x10-8 M) [46]
AKN-028 Hs Inhibition 7.5 pIC50 11
pIC50 7.5 (IC50 2.9x10-8 M) [11]
Description: Inhibition of KIT autophosphorylation in human AML M07 cells which overexpress KIT
CHMFL-KIT-8140 Hs Inhibition 7.5 pIC50 31
pIC50 7.5 (IC50 3.3x10-8 M) [31]
compound 19a [PMID: 30503936] Hs Inhibition 7.2 pIC50 41
pIC50 7.2 (IC50 6.4x10-8 M) [41]
sorafenib Hs Inhibition 7.2 pIC50 53,55
pIC50 7.2 (IC50 6.8x10-8 M) [55]
pIC50 7.2 (IC50 6.8x10-8 M) [53]
avapritinib Hs Inhibition 7.1 pIC50 12
pIC50 7.1 (IC50 7.3x10-8 M) [12]
OSI-930 Hs Inhibition 6.4 – 7.6 pIC50 19
pIC50 6.4 – 7.6 (IC50 4x10-7 – 2.5x10-8 M) [19]
Description: The IC50 varied dependent on whether KIT was activated or unactivated, with the lower value measured for the activated enzyme.
pazopanib Hs Inhibition 6.8 pIC50 24
pIC50 6.8 (IC50 1.4x10-7 M) [24]
tandutinib Hs Inhibition 6.8 pIC50 28
pIC50 6.8 (IC50 1.7x10-7 M) [28]
masitinib Hs Inhibition 6.7 pIC50 10
pIC50 6.7 (IC50 2x10-7 M) [10]
CP-673451 Hs Inhibition 6.6 pIC50 43
pIC50 6.6 (IC50 2.52x10-7 M) [43]
GTP-14564 Hs Inhibition 6.5 pIC50 36
pIC50 6.5 (IC50 3x10-7 M) [36]
semaxanib Hs Inhibition 6.4 pIC50 6
pIC50 6.4 (IC50 4x10-7 M) [6]
apatinib Hs Inhibition 6.4 pIC50 48
pIC50 6.4 (IC50 4.29x10-7 M) [48]
Description: Assay used apatinib mesylate (YN968D1)
Ki-20227 Hs Inhibition 6.3 pIC50 37
pIC50 6.3 (IC50 4.51x10-7 M) [37]
AST-487 Hs Inhibition 6.3 pIC50 1
pIC50 6.3 (IC50 5x10-7 M) [1]
Description: In vitro inhibition of c-Kit
lucitanib Hs Inhibition 6.3 pIC50 57
pIC50 6.3 (IC50 5.27x10-7 M) [57]
flumatinib Hs Inhibition 6.2 pIC50 33
pIC50 6.2 (IC50 6.66x10-7 M) [33]
BLZ945 Hs Inhibition 5.4 pIC50 45
pIC50 5.4 (IC50 3.88x10-6 M) [45]
ripretinib Hs Inhibition - - 14
[14]
Inhibitor Comments
Note that the primary target of avapritinib (BLU-285) is mutant, constitutively active KIT rather than the wild type kinase [12].
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
stem cell factor {Sp: Human} Hs Agonist 9.6 – 9.8 pKd 51
pKd 9.6 – 9.8 (Kd 2.4x10-10 – 1.5x10-10 M) [51]
Description: Binding affinity of KIT receptors on cell membranes from OCIM1, MO7e and HEL cells, using 125I-SCF as radioligand.
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 9,54

Key to terms and symbols Click column headers to sort
Target used in screen: KIT
Ligand Sp. Type Action Value Parameter
sunitinib Hs Inhibitor Inhibition 9.4 pKd
cediranib Hs Inhibitor Inhibition 9.4 pKd
SU-14813 Hs Inhibitor Inhibition 9.2 pKd
Ki-20227 Hs Inhibitor Inhibition 9.2 pKd
dasatinib Hs Inhibitor Inhibition 9.1 pKd
PD-173955 Hs Inhibitor Inhibition 8.7 pKd
linifanib Hs Inhibitor Inhibition 8.7 pKd
foretinib Hs Inhibitor Inhibition 8.6 pKd
tandutinib Hs Inhibitor Inhibition 8.6 pKd
pazopanib Hs Inhibitor Inhibition 8.6 pKd
Target used in screen: KIT(A829P)
Ligand Sp. Type Action Value Parameter
staurosporine Hs Inhibitor Inhibition 9.2 pKd
dasatinib Hs Inhibitor Inhibition 9.2 pKd
foretinib Hs Inhibitor Inhibition 8.5 pKd
tamatinib Hs Inhibitor Inhibition 8.5 pKd
quizartinib Hs Inhibitor Inhibition 8.4 pKd
AST-487 Hs Inhibitor Inhibition 8.4 pKd
masitinib Hs Inhibitor Inhibition 7.9 pKd
motesanib Hs Inhibitor Inhibition 7.8 pKd
imatinib Hs Inhibitor Inhibition 7.8 pKd
linifanib Hs Inhibitor Inhibition 7.8 pKd
Target used in screen: KIT(D816H)
Ligand Sp. Type Action Value Parameter
staurosporine Hs Inhibitor Inhibition 9.4 pKd
dasatinib Hs Inhibitor Inhibition 8.8 pKd
tamatinib Hs Inhibitor Inhibition 8.2 pKd
lestaurtinib Hs Inhibitor Inhibition 8.0 pKd
midostaurin Hs Inhibitor Inhibition 7.8 pKd
foretinib Hs Inhibitor Inhibition 7.4 pKd
JNJ-28312141 Hs Inhibitor Inhibition 7.3 pKd
AST-487 Hs Inhibitor Inhibition 7.2 pKd
sunitinib Hs Inhibitor Inhibition 7.0 pKd
tandutinib Hs Inhibitor Inhibition 6.9 pKd
Target used in screen: KIT(D816V)
Ligand Sp. Type Action Value Parameter
staurosporine Hs Inhibitor Inhibition 9.2 pKd
tamatinib Hs Inhibitor Inhibition 8.6 pKd
dasatinib Hs Inhibitor Inhibition 8.6 pKd
lestaurtinib Hs Inhibitor Inhibition 8.1 pKd
midostaurin Hs Inhibitor Inhibition 8.1 pKd
foretinib Hs Inhibitor Inhibition 8.0 pKd
JNJ-28312141 Hs Inhibitor Inhibition 7.7 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.6 pKd
tandutinib Hs Inhibitor Inhibition 7.5 pKd
PD-173955 Hs Inhibitor Inhibition 7.5 pKd
Target used in screen: KIT(L576P)
Ligand Sp. Type Action Value Parameter
SU-14813 Hs Inhibitor Inhibition 9.5 pKd
cediranib Hs Inhibitor Inhibition 9.3 pKd
dasatinib Hs Inhibitor Inhibition 9.2 pKd
Ki-20227 Hs Inhibitor Inhibition 9.1 pKd
motesanib Hs Inhibitor Inhibition 8.9 pKd
sunitinib Hs Inhibitor Inhibition 8.9 pKd
dovitinib Hs Inhibitor Inhibition 8.8 pKd
axitinib Hs Inhibitor Inhibition 8.8 pKd
pazopanib Hs Inhibitor Inhibition 8.7 pKd
linifanib Hs Inhibitor Inhibition 8.7 pKd
Target used in screen: KIT(V559D)
Ligand Sp. Type Action Value Parameter
cediranib Hs Inhibitor Inhibition 9.6 pKd
sunitinib Hs Inhibitor Inhibition 9.4 pKd
Ki-20227 Hs Inhibitor Inhibition 9.3 pKd
axitinib Hs Inhibitor Inhibition 9.3 pKd
SU-14813 Hs Inhibitor Inhibition 9.3 pKd
dasatinib Hs Inhibitor Inhibition 9.2 pKd
PD-173955 Hs Inhibitor Inhibition 8.8 pKd
linifanib Hs Inhibitor Inhibition 8.8 pKd
foretinib Hs Inhibitor Inhibition 8.7 pKd
pazopanib Hs Inhibitor Inhibition 8.6 pKd
Target used in screen: KIT(V559D,T670I)
Ligand Sp. Type Action Value Parameter
sunitinib Hs Inhibitor Inhibition 9.6 pKd
cediranib Hs Inhibitor Inhibition 9.5 pKd
SU-14813 Hs Inhibitor Inhibition 9.3 pKd
axitinib Hs Inhibitor Inhibition 8.9 pKd
foretinib Hs Inhibitor Inhibition 8.6 pKd
linifanib Hs Inhibitor Inhibition 8.4 pKd
quizartinib Hs Inhibitor Inhibition 8.2 pKd
pazopanib Hs Inhibitor Inhibition 8.2 pKd
barasertib-hQPA Hs Inhibitor Inhibition 8.1 pKd
staurosporine Hs Inhibitor Inhibition 8.0 pKd
Target used in screen: KIT(V559D,V654A)
Ligand Sp. Type Action Value Parameter
sunitinib Hs Inhibitor Inhibition 9.7 pKd
SU-14813 Hs Inhibitor Inhibition 9.6 pKd
cediranib Hs Inhibitor Inhibition 9.5 pKd
dasatinib Hs Inhibitor Inhibition 8.6 pKd
dovitinib Hs Inhibitor Inhibition 8.5 pKd
Ki-20227 Hs Inhibitor Inhibition 8.5 pKd
axitinib Hs Inhibitor Inhibition 8.5 pKd
masitinib Hs Inhibitor Inhibition 8.3 pKd
JNJ-28312141 Hs Inhibitor Inhibition 8.2 pKd
foretinib Hs Inhibitor Inhibition 8.1 pKd
Target used in screen: KIT-autoinhibited
Ligand Sp. Type Action Value Parameter
dasatinib Hs Inhibitor Inhibition 8.9 pKd
sunitinib Hs Inhibitor Inhibition 8.5 pKd
Ki-20227 Hs Inhibitor Inhibition 7.3 pKd
PD-173955 Hs Inhibitor Inhibition 7.0 pKd
quizartinib Hs Inhibitor Inhibition 6.7 pKd
staurosporine Hs Inhibitor Inhibition 6.3 pKd
AST-487 Hs Inhibitor Inhibition 5.9 pKd
vatalanib Hs Inhibitor Inhibition 5.8 pKd
sorafenib Hs Inhibitor Inhibition 5.7 pKd
imatinib 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
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: 3,18

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 Hs Inhibitor Inhibition 3.3
sunitinib Hs Inhibitor Inhibition 8.7
staurosporine Hs Inhibitor Inhibition 8.7 9.5 1.0
dovitinib Hs Inhibitor Inhibition 9.9
pazopanib Hs Inhibitor Inhibition 10.9
Flt-3 inhibitor III Hs Inhibitor Inhibition 20.3 1.0 1.0
dorsomorphin Hs Inhibitor Inhibition 21.4 5.0 2.0
Lck inhibitor Hs Inhibitor Inhibition 21.6 36.0 1.0
PDK1/Akt/Flt dual pathway inhibitor Hs Inhibitor Inhibition 22.2 114.0 96.0
PDGF receptor tyrosine kinase inhibitor IV 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 [22]. 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) [44]. Experimental bispecific antibodies crosslinking KIT with inhibitory CD300a inhibit human mast cell differentiation and CBMC survival and activation [4]. Additional strategies targeting the KIT pathway in allergic inflammatory disease are reviewed in [27].
Cell Type Associations
Immuno Cell Type:  Mast cells
Cell Ontology Term:   mast cell (CL:0000097)