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

Target id: 1805

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

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 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
piebald trait
c-kit receptor tyrosine kinase
mast/stem cell growth factor receptor
p145 c-kit
Proto-oncogene c-Kit
Steel Factor Receptor
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:  Crystal structure of the extracellular domain of the receptor tyrosine kinase, Kit
PDB Id:  2EC8
Resolution:  3.0Å
Species:  Human
References:  14
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:  6
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
crenolanib Hs Inhibition 7.11 pKd 8
pKd 7.11 (Kd 7.8x10-8 M) [8]
cediranib Hs Inhibition 8.52 pIC50 12
pIC50 8.52 (IC50 3x10-9 M) [12]
dovitinib Hs Inhibition 8.52 pIC50 10
pIC50 8.52 (IC50 3x10-9 M) [10]
SU11652 Hs Inhibition 8.0 pIC50 5
pIC50 8.0 (IC50 1x10-8 M) [5]
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]
GTP-14564 Hs Inhibition 6.52 pIC50 9
pIC50 6.52 (IC50 3x10-7 M) [9]
apatinib Hs Inhibition 6.37 pIC50 11
pIC50 6.37 (IC50 4.29x10-7 M) [11]
Description: Assay used apatinib mesylate (YN968D1)
lucitanib Hs Inhibition 6.28 pIC50 15
pIC50 6.28 (IC50 5.27x10-7 M) [15]
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: 3,13

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
NVP-TAE684 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: 2,7

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:  Acute myeloblastic leukemia with maturation
Orphanet:  98834
Disease:  Acute myeloid leukemia with abnormal bone marrow eosinophils
Orphanet:  98829
Disease:  Acute myeloid leukemia with t(8;21)(q22;q22) translocation
Orphanet:  102724
Disease:  Aleukemic mast cell leukemia
Orphanet:  158799
Disease:  Bullous diffuse cutaneous mastocytosis
Orphanet:  280785
Disease:  Classic mast cell leukemia
Orphanet:  158796
Disease:  Cutaneous mastocytoma
Orphanet:  79455
Disease:  Gastrointestinal stromal tumor, familial
OMIM:  606764
Orphanet:  44890
Disease:  Isolated bone marrow mastocytosis
Orphanet:  158778
Disease:  Leukemia, acute myeloid
OMIM:  601626
Disease:  Lymphoadenopathic mastocytosis with eosinophilia
Orphanet:  158793
Disease:  Nodular urticaria pigmentosa
Orphanet:  158772
Disease:  Piebaldism
OMIM:  172800
Orphanet:  2884
Disease:  Plaque-form urticaria pigmentosa
Orphanet:  158769
Disease:  Pseudoxanthomatous diffuse cutaneous mastocytosis
Orphanet:  280794
Disease:  Smouldering systemic mastocytosis
Orphanet:  158775
Disease:  Systemic mastocytosis with an associated clonal hematologic non-mast cell lineage disease
Orphanet:  98849
Disease:  Telangiectasia macularis eruptiva perstans
Orphanet:  90389
Disease:  Testicular germ cell tumor
OMIM:  273300
Disease:  Typical urticaria pigmentosa
Orphanet:  158766

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. 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. U.S.A.104 (51): 20523-8. [PMID:18077363]

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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]

12. 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]

13. 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]

14. 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]

15. 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]

How to cite this page

Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family: v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog. Last modified on 05/11/2014. Accessed on 21/12/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1805.