v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog

Nomenclature: v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog

Abbreviated Name: Kit

Family: Receptor tyrosine kinases

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Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 976 4q11-q12 KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
Mouse 1 979 5 Kit kit oncogene
Rat - 978 14p11 Kit v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
Previous and Unofficial Names
CD117
C-Kit
PBT
stem cell growth factor receptor
SCFR
piebald trait
protein kinase
c-kit receptor tyrosine kinase
mast/stem cell growth factor receptor
Steel Factor Receptor
Dominant white spotting
belly-spot
Tr-kit
SCO1
SCO5
SOW3
Gsfsco1
Gsfsco5
Gsfsow3
Proto-oncogene c-Kit
p145 c-kit
Database Links
BRENDA
Ensembl Gene
Entrez Gene
ExplorEnz
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG BRITE Hierarchy
KEGG Gene
OMIM
Orphanet Gene
PhosphoSitePlus
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  KIT kinase domain in complex with sunitinib
PDB Id:  3GOE
Ligand:  sunitinib
Resolution:  1.6Å
Species:  Human
References:  5
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:  10
Enzyme Reaction
EC Number: 2.7.10.1
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
cediranib Hs Inhibition 8.52 pIC50 8
pIC50 8.52 (IC50 3x10-9 M) [8]
dovitinib Hs Inhibition 8.52 pIC50 7
pIC50 8.52 (IC50 3x10-9 M) [7]
linifanib Hs Inhibition 7.85 pIC50 1
pIC50 7.85 (IC50 1.4x10-8 M) [1]
masitinib Hs Inhibition 6.7 pIC50 4
pIC50 6.7 (IC50 2x10-7 M) [4]
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: 3,9

Key to terms and symbols Click column headers to sort
Target used in screen: KIT
Ligand Sp. Type Action Affinity Units
sunitinib Hs Inhibitor Inhibition 9.43 pKd
cediranib Hs Inhibitor Inhibition 9.42 pKd
SU-14813 Hs Inhibitor Inhibition 9.17 pKd
Ki-20227 Hs Inhibitor Inhibition 9.16 pKd
dasatinib Hs Inhibitor Inhibition 9.09 pKd
PD-173955 Hs Inhibitor Inhibition 8.74 pKd
linifanib Hs Inhibitor Inhibition 8.7 pKd
foretinib Hs Inhibitor Inhibition 8.6 pKd
tandutinib Hs Inhibitor Inhibition 8.57 pKd
pazopanib Hs Inhibitor Inhibition 8.55 pKd
Target used in screen: KIT(A829P)
Ligand Sp. Type Action Affinity Units
staurosporine Hs Inhibitor Inhibition 9.22 pKd
dasatinib Hs Inhibitor Inhibition 9.18 pKd
foretinib Hs Inhibitor Inhibition 8.49 pKd
R406 Hs Inhibitor Inhibition 8.46 pKd
quizartinib Hs Inhibitor Inhibition 8.44 pKd
AST-487 Hs Inhibitor Inhibition 8.36 pKd
masitinib Hs Inhibitor Inhibition 7.92 pKd
motesanib Hs Inhibitor Inhibition 7.82 pKd
imatinib Hs Inhibitor Inhibition 7.82 pKd
linifanib Hs Inhibitor Inhibition 7.77 pKd
Target used in screen: KIT(D816H)
Ligand Sp. Type Action Affinity Units
staurosporine Hs Inhibitor Inhibition 9.37 pKd
dasatinib Hs Inhibitor Inhibition 8.8 pKd
R406 Hs Inhibitor Inhibition 8.19 pKd
lestaurtinib Hs Inhibitor Inhibition 7.96 pKd
midostaurin Hs Inhibitor Inhibition 7.8 pKd
foretinib Hs Inhibitor Inhibition 7.44 pKd
JNJ-28312141 Hs Inhibitor Inhibition 7.32 pKd
AST-487 Hs Inhibitor Inhibition 7.17 pKd
sunitinib Hs Inhibitor Inhibition 6.96 pKd
tandutinib Hs Inhibitor Inhibition 6.92 pKd
Target used in screen: KIT(D816V)
Ligand Sp. Type Action Affinity Units
staurosporine Hs Inhibitor Inhibition 9.19 pKd
R406 Hs Inhibitor Inhibition 8.6 pKd
dasatinib Hs Inhibitor Inhibition 8.59 pKd
lestaurtinib Hs Inhibitor Inhibition 8.15 pKd
midostaurin Hs Inhibitor Inhibition 8.11 pKd
foretinib Hs Inhibitor Inhibition 8.02 pKd
JNJ-28312141 Hs Inhibitor Inhibition 7.74 pKd
TAE 684 Hs Inhibitor Inhibition 7.59 pKd
tandutinib Hs Inhibitor Inhibition 7.54 pKd
PD-173955 Hs Inhibitor Inhibition 7.46 pKd
Target used in screen: KIT(L576P)
Ligand Sp. Type Action Affinity Units
SU-14813 Hs Inhibitor Inhibition 9.54 pKd
cediranib Hs Inhibitor Inhibition 9.27 pKd
dasatinib Hs Inhibitor Inhibition 9.24 pKd
Ki-20227 Hs Inhibitor Inhibition 9.07 pKd
motesanib Hs Inhibitor Inhibition 8.89 pKd
sunitinib Hs Inhibitor Inhibition 8.89 pKd
dovitinib Hs Inhibitor Inhibition 8.8 pKd
axitinib Hs Inhibitor Inhibition 8.77 pKd
pazopanib Hs Inhibitor Inhibition 8.74 pKd
linifanib Hs Inhibitor Inhibition 8.72 pKd
Target used in screen: KIT(V559D)
Ligand Sp. Type Action Affinity Units
cediranib Hs Inhibitor Inhibition 9.57 pKd
sunitinib Hs Inhibitor Inhibition 9.39 pKd
Ki-20227 Hs Inhibitor Inhibition 9.34 pKd
axitinib Hs Inhibitor Inhibition 9.31 pKd
SU-14813 Hs Inhibitor Inhibition 9.29 pKd
dasatinib Hs Inhibitor Inhibition 9.17 pKd
PD-173955 Hs Inhibitor Inhibition 8.8 pKd
linifanib Hs Inhibitor Inhibition 8.77 pKd
foretinib Hs Inhibitor Inhibition 8.68 pKd
pazopanib Hs Inhibitor Inhibition 8.64 pKd
Target used in screen: KIT(V559D,T670I)
Ligand Sp. Type Action Affinity Units
sunitinib Hs Inhibitor Inhibition 9.55 pKd
cediranib Hs Inhibitor Inhibition 9.49 pKd
SU-14813 Hs Inhibitor Inhibition 9.25 pKd
axitinib Hs Inhibitor Inhibition 8.85 pKd
foretinib Hs Inhibitor Inhibition 8.62 pKd
linifanib Hs Inhibitor Inhibition 8.42 pKd
quizartinib Hs Inhibitor Inhibition 8.22 pKd
pazopanib Hs Inhibitor Inhibition 8.19 pKd
barasertib-hQPA Hs Inhibitor Inhibition 8.1 pKd
staurosporine Hs Inhibitor Inhibition 8.02 pKd
Target used in screen: KIT(V559D,V654A)
Ligand Sp. Type Action Affinity Units
sunitinib Hs Inhibitor Inhibition 9.68 pKd
SU-14813 Hs Inhibitor Inhibition 9.6 pKd
cediranib Hs Inhibitor Inhibition 9.51 pKd
dasatinib Hs Inhibitor Inhibition 8.57 pKd
dovitinib Hs Inhibitor Inhibition 8.51 pKd
Ki-20227 Hs Inhibitor Inhibition 8.49 pKd
axitinib Hs Inhibitor Inhibition 8.46 pKd
masitinib Hs Inhibitor Inhibition 8.33 pKd
JNJ-28312141 Hs Inhibitor Inhibition 8.22 pKd
foretinib Hs Inhibitor Inhibition 8.12 pKd
Target used in screen: KIT-autoinhibited
Ligand Sp. Type Action Affinity Units
dasatinib Hs Inhibitor Inhibition 8.92 pKd
sunitinib Hs Inhibitor Inhibition 8.52 pKd
Ki-20227 Hs Inhibitor Inhibition 7.27 pKd
PD-173955 Hs Inhibitor Inhibition 7.04 pKd
quizartinib Hs Inhibitor Inhibition 6.72 pKd
staurosporine Hs Inhibitor Inhibition 6.34 pKd
AST-487 Hs Inhibitor Inhibition 5.92 pKd
vatalanib Hs Inhibitor Inhibition 5.82 pKd
sorafenib Hs Inhibitor Inhibition 5.66 pKd
imatinib Hs Inhibitor Inhibition 5.35 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: 2,6

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 »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Cutaneous mastocytoma
Orphanet:  79455
References: 
Mutations not determined
Disease:  Leukemia, acute myeloid
OMIM:  601626
References: 
Mutations not determined
Disease:  Piebaldism
OMIM:  172800
Orphanet:  2884
References: 
Mutations not determined
Disease:  Classic mast cell leukemia
Orphanet:  158796
References: 
Mutations not determined
Disease:  Acute myeloblastic leukemia with maturation
Orphanet:  98834
References: 
Mutations not determined
Disease:  Acute myeloid leukemia with abnormal bone marrow eosinophils
Orphanet:  98829
References: 
Mutations not determined
Disease:  Acute myeloid leukemia with t(8;21)(q22;q22) translocation
Orphanet:  102724
References: 
Mutations not determined
Disease:  Aleukemic mast cell leukemia
Orphanet:  158799
References: 
Mutations not determined
Disease:  Bullous diffuse cutaneous mastocytosis
Orphanet:  280785
References: 
Mutations not determined
Disease:  Gastrointestinal stromal tumor, familial
OMIM:  606764
Orphanet:  44890
References: 
Mutations not determined
Disease:  Isolated bone marrow mastocytosis
Orphanet:  158778
References: 
Mutations not determined
Disease:  Lymphoadenopathic mastocytosis with eosinophilia
Orphanet:  158793
References: 
Mutations not determined
Disease:  Nodular urticaria pigmentosa
Orphanet:  158772
References: 
Mutations not determined
Disease:  Plaque-form urticaria pigmentosa
Orphanet:  158769
References: 
Mutations not determined
Disease:  Pseudoxanthomatous diffuse cutaneous mastocytosis
Orphanet:  280794
References: 
Mutations not determined
Disease:  Typical urticaria pigmentosa
Orphanet:  158766
References: 
Mutations not determined
Disease:  Smouldering systemic mastocytosis
Orphanet:  158775
References: 
Mutations not determined
Disease:  Systemic mastocytosis with an associated clonal hematologic non-mast cell lineage disease
Orphanet:  98849
References: 
Mutations not determined
Disease:  Telangiectasia macularis eruptiva perstans
Orphanet:  90389
References: 
Mutations not determined
Disease:  Testicular germ cell tumor
OMIM:  273300
References: 
Mutations not determined

References

Show »

1. 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]

2. 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]

3. 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]

4. 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 ONE4 (9): e7258. [PMID:19789626]

5. 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. U.S.A.106 (5): 1542-7. [PMID:19164557]

6. 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]

7. 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]

8. 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]

9. 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]

10. 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. Cell130 (2): 323-34. [PMID:17662946]

How to cite this page

Receptor tyrosine kinases: v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog. Last modified on 13/05/2014. Accessed on 30/07/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1805.