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polo like kinase 4

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Target not currently curated in GtoImmuPdb

Target id: 2171

Nomenclature: polo like kinase 4

Abbreviated Name: PLK4

Family: Polo-like kinase (PLK) family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 970 4q28.1 PLK4 polo like kinase 4
Mouse - 925 3 B Plk4 polo like kinase 4
Rat - 924 2q25 Plk4 polo-like kinase 4
Previous and Unofficial Names Click here for help
serine/threonine kinase 18 | serine/threonine-protein kinase Sak | STK18 | polo-like kinase 4
Database Links Click here for help
Alphafold O00444 (Hs), Q64702 (Mm), B2GUY1 (Rn)
BRENDA 2.7.11.21
CATH/Gene3D 3.30.1120.30
ChEMBL Target CHEMBL3788 (Hs)
Ensembl Gene ENSG00000142731 (Hs), ENSMUSG00000025758 (Mm), ENSRNOG00000011654 (Rn)
Entrez Gene 10733 (Hs), 20873 (Mm), 310344 (Rn)
Human Protein Atlas ENSG00000142731 (Hs)
KEGG Enzyme 2.7.11.21
KEGG Gene hsa:10733 (Hs), mmu:20873 (Mm), rno:310344 (Rn)
OMIM 605031 (Hs)
Pharos O00444 (Hs)
RefSeq Nucleotide NM_001190799 (Hs), NM_011495 (Mm), NM_001107669 (Rn)
RefSeq Protein NP_055079 (Hs), NP_775261 (Mm), NP_001101139 (Rn)
UniProtKB O00444 (Hs), Q64702 (Mm), B2GUY1 (Rn)
Wikipedia PLK4 (Hs)
Selected 3D Structures Click here for help
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 Click here for help
EC Number: 2.7.11.21

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
RG-1530 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 pKd 6
⤷ pKd 8.0 (Kd 1.1x10-8 M) [6]
XMD8-92 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 pKd 8
⤷ pKd 6.2 (Kd 6x10-7 M) [8]
CZS-241 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.6 pIC50 5
⤷ pIC50 8.6 (IC50 2.6x10-9 M) [5]
ocifisertib Small molecule or natural product Primary target of this compound Hs Inhibition 8.6 pIC50 4
⤷ pIC50 8.6 (IC50 2.8x10-9 M) [4]
axitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pIC50 3
⤷ pIC50 7.3 (IC50 4.6x10-8 M) [3]
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: 2,7
Key to terms and symbols Click column headers to sort
Target used in screen: PLK4
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.1 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.8 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 8.4 pKd
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
axitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 7.7 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 7.5 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.2 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology Click here for help
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. Elife, 4. [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 Cell, 26 (2): 163-76. [PMID:25043604]

5. Sun Y, Xue Y, Liu H, Mu S, Sun P, Sun Y, Wang L, Wang H, Wang J, Wu T et al.. (2023) Discovery of CZS-241: A Potent, Selective, and Orally Available Polo-Like Kinase 4 Inhibitor for the Treatment of Chronic Myeloid Leukemia. J Med Chem, 66 (4): 2396-2421. [PMID:36734825]

6. 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]

7. 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]

8. 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 Cell, 18 (3): 258-67. [PMID:20832753]

How to cite this page

Polo-like kinase (PLK) family: polo like kinase 4. Last modified on 23/02/2023. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2171.