polo like kinase 4

Target id: 2171

Nomenclature: polo like kinase 4

Abbreviated Name: PLK4

Family: Polo-like kinase (PLK) family

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

   GtoImmuPdb view: OFF :     Currently no data for polo like kinase 4 in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 970 4q27-q28 PLK4 polo like kinase 4
Mouse - 898 3 B Plk4 polo-like kinase 4
Rat - 869 2 q26 Plk4 polo-like kinase 4
Previous and Unofficial Names
serine/threonine kinase 18 | serine/threonine-protein kinase Sak | STK18 | polo-like kinase 4
Database Links
BRENDA
CATH/Gene3D
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of PLK4 kinase
PDB Id:  3COK
Resolution:  2.25Å
Species:  Human
References: 
Image of receptor 3D structure from RCSB PDB
Description:  STIL binding to Polo-box 3 of PLK4 regulates centriole duplication-Solution NMR
PDB Id:  2N19
Resolution:  0.0Å
Species:  Human
References:  1
Enzyme Reaction
EC Number: 2.7.11.21

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 Affinity Units Reference
XMD8-92 Hs Inhibition 6.2 pKd 6
pKd 6.2 (Kd 6x10-7 M) [6]
CFI-400945 Hs Inhibition 8.6 pIC50 4
pIC50 8.6 (IC50 2.8x10-9 M) [4]
axitinib Hs Inhibition 7.3 pIC50 3
pIC50 7.3 (IC50 4.6x10-8 M) [3]
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: 2,5

Key to terms and symbols Click column headers to sort
Target used in screen: PLK4
Ligand Sp. Type Action Affinity Units
staurosporine Hs Inhibitor Inhibition 9.1 pKd
NVP-TAE684 Hs Inhibitor Inhibition 9.0 pKd
lestaurtinib Hs Inhibitor Inhibition 8.8 pKd
foretinib Hs Inhibitor Inhibition 8.5 pKd
tamatinib Hs Inhibitor Inhibition 8.4 pKd
tozasertib Hs Inhibitor Inhibition 8.0 pKd
axitinib Hs Inhibitor Inhibition 7.8 pKd
KW-2449 Hs Inhibitor Inhibition 7.7 pKd
JNJ-28312141 Hs Inhibitor Inhibition 7.5 pKd
crizotinib Hs Inhibitor Inhibition 7.2 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Microcephaly and chorioretinopathy, autosomal recessive, 2; MCCRP2
OMIM: 616171

References

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1. Arquint C, Gabryjonczyk AM, Imseng S, Böhm R, Sauer E, Hiller S, Nigg EA, Maier T. (2015) STIL binding to Polo-box 3 of PLK4 regulates centriole duplication. Elife4. [PMID:26188084]

2. 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]

3. Laufer R, Forrest B, Li SW, Liu Y, Sampson P, Edwards L, Lang Y, Awrey DE, Mao G, Plotnikova O et al.. (2013) The discovery of PLK4 inhibitors: (E)-3-((1H-Indazol-6-yl)methylene)indolin-2-ones as novel antiproliferative agents. J. Med. Chem.56 (15): 6069-87. [PMID:23829549]

4. Mason JM, Lin DC, Wei X, Che Y, Yao Y, Kiarash R, Cescon DW, Fletcher GC, Awrey DE, Bray MR et al.. (2014) Functional characterization of CFI-400945, a Polo-like kinase 4 inhibitor, as a potential anticancer agent. Cancer Cell26 (2): 163-76. [PMID:25043604]

5. 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]

6. Yang Q, Deng X, Lu B, Cameron M, Fearns C, Patricelli MP, Yates 3rd JR, Gray NS, Lee JD. (2010) Pharmacological inhibition of BMK1 suppresses tumor growth through promyelocytic leukemia protein. Cancer Cell18 (3): 258-67. [PMID:20832753]

How to cite this page

Polo-like kinase (PLK) family: polo like kinase 4. Last modified on 29/01/2016. Accessed on 22/11/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2171.