polo like kinase 1 | Polo-like kinase (PLK) family | IUPHAR/BPS Guide to PHARMACOLOGY

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polo like kinase 1

Target not currently curated in GtoImmuPdb

Target id: 2168

Nomenclature: polo like kinase 1

Abbreviated Name: PLK1

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

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 603 16p PLK1 polo like kinase 1
Mouse - 603 7 F3 Plk1 polo like kinase 1
Rat - 603 1 q36 Plk1 polo-like kinase 1
Previous and Unofficial Names
STPK13 | polo-like kinase 1
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Polo-like kinase I Polo-box domain in complex with MQSpTPL phosphopeptide
PDB Id:  3P34
Resolution:  1.4Å
Species:  Human
References:  15
Image of receptor 3D structure from RCSB PDB
Description:  Structure of PLK1 in complex with BI2536
PDB Id:  2RKU
Ligand:  BI-2536
Resolution:  1.95Å
Species:  Human
References:  10
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of polo-like kinase 1 in complex with NMS-P937
PDB Id:  2YAC
Ligand:  NMS-P937
Resolution:  2.2Å
Species:  Human
References:  2
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 Value Parameter Reference
Ro3280 Hs Inhibition 10.1 pKd 3
pKd 10.1 (Kd 9x10-11 M) [3]
Description: Ambit selectivity screen at 1μM Ro3280.
GSK-461364A Hs Inhibition 9.3 pKi 9
pKi 9.3 (Ki 5x10-10 M) [9]
BI-2536 Hs Inhibition 8.5 pKi 14
pKi 8.5 (Ki 3x10-9 M) [14]
BI-2536 Hs Inhibition 9.1 pIC50 12
pIC50 9.1 (IC50 8.3x10-10 M) [12]
volasertib Hs Inhibition 9.1 pIC50 14
pIC50 9.1 (IC50 8.7x10-10 M) [14]
NMS-P937 Hs Inhibition 8.7 pIC50 2
pIC50 8.7 (IC50 2x10-9 M) [2]
GSK579289A Hs Inhibition 8.7 pIC50 6
pIC50 8.7 (IC50 2x10-9 M) [6]
compound 2 [PMID: 19097784] Hs Inhibition 8.7 pIC50 7
pIC50 8.7 (IC50 2x10-9 M) [7]
MLN0905 Hs Inhibition 8.7 pIC50 5
pIC50 8.7 (IC50 2x10-9 M) [5]
Ro3280 Hs Inhibition 8.5 pIC50 3
pIC50 8.5 (IC50 3x10-9 M) [3]
Description: In a biochemical enzymatic assay.
GW853606 Hs Inhibition 8.1 pIC50 7
pIC50 8.1 (IC50 9x10-9 M) [7]
compound 6 [PMID: 30125504] Hs Inhibition 8.0 pIC50 11
pIC50 8.0 (IC50 9.9x10-9 M) [11]
Description: Biochemical inhibition of PLK1.
dual BRD4/PLK1 inhibitor 23 Hs Inhibition 7.4 pIC50 11
pIC50 7.4 (IC50 4x10-8 M) [11]
Description: Biochemical inhibition of PLK1.
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: 4,13

Key to terms and symbols Click column headers to sort
Target used in screen: PLK1
Ligand Sp. Type Action Value Parameter
GSK-461364A Hs Inhibitor Inhibition 10.0 pKd
BI-2536 Hs Inhibitor Inhibition 9.7 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.7 pKd
GSK-1838705A Hs Inhibitor Inhibition 7.3 pKd
ruxolitinib Hs Inhibitor Inhibition 6.9 pKd
staurosporine Hs Inhibitor Inhibition 6.7 pKd
lestaurtinib Hs Inhibitor Inhibition 6.7 pKd
fedratinib Hs Inhibitor Inhibition 6.6 pKd
tamatinib Hs Inhibitor Inhibition 6.1 pKd
bosutinib Hs Inhibitor Inhibition 5.7 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: 1,8

Key to terms and symbols Click column headers to sort
Target used in screen: Plk1/PLK1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
wortmannin Hs Inhibitor Inhibition 2.4
JAK inhibitor I Hs Inhibitor Inhibition 10.5 14.0 17.0
PDK1/Akt/Flt dual pathway inhibitor Hs Inhibitor Inhibition 28.6 103.0 64.0
staurosporine Hs Inhibitor Inhibition 36.9 48.5 6.5
compound 52 [PMID: 9677190] Hs Inhibitor Inhibition 44.1 30.0 6.0
K-252a Hs Inhibitor Inhibition 46.2 50.0 17.0
SB 218078 Hs Inhibitor Inhibition 50.2 88.0 112.0
isogranulatimide Hs Inhibitor Inhibition 50.8 62.0 60.0
aminopurvalanol A Hs Inhibitor Inhibition 54.9 50.0 9.0
AG 112 Hs Inhibitor Inhibition 60.8 79.0 36.0
Displaying the top 10 most potent ligands  View all ligands in screen »

References

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1. 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]

2. Beria I, Bossi RT, Brasca MG, Caruso M, Ceccarelli W, Fachin G, Fasolini M, Forte B, Fiorentini F, Pesenti E et al.. (2011) NMS-P937, a 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivative as potent and selective Polo-like kinase 1 inhibitor. Bioorg. Med. Chem. Lett., 21 (10): 2969-74. [PMID:21470862]

3. Chen S, Bartkovitz D, Cai J, Chen Y, Chen Z, Chu XJ, Le K, Le NT, Luk KC, Mischke S et al.. (2012) Identification of novel, potent and selective inhibitors of Polo-like kinase 1. Bioorg. Med. Chem. Lett., 22 (2): 1247-50. [PMID:22172702]

4. 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]

5. Duffey MO, Vos TJ, Adams R, Alley J, Anthony J, Barrett C, Bharathan I, Bowman D, Bump NJ, Chau R et al.. (2012) Discovery of a potent and orally bioavailable benzolactam-derived inhibitor of Polo-like kinase 1 (MLN0905). J. Med. Chem., 55 (1): 197-208. [PMID:22070629]

6. Emmitte KA, Adjabeng GM, Adjebang GM, Andrews CW, Alberti JG, Bambal R, Chamberlain SD, Davis-Ward RG, Dickson HD, Hassler DF et al.. (2009) Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding. Bioorg. Med. Chem. Lett., 19 (6): 1694-7. [PMID:19237286]

7. Emmitte KA, Andrews CW, Badiang JG, Davis-Ward RG, Dickson HD, Drewry DH, Emerson HK, Epperly AH, Hassler DF, Knick VB et al.. (2009) Discovery of thiophene inhibitors of polo-like kinase. Bioorg. Med. Chem. Lett., 19 (3): 1018-21. [PMID:19097784]

8. 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]

9. Gilmartin AG, Bleam MR, Richter MC, Erskine SG, Kruger RG, Madden L, Hassler DF, Smith GK, Gontarek RR, Courtney MP et al.. (2009) Distinct concentration-dependent effects of the polo-like kinase 1-specific inhibitor GSK461364A, including differential effect on apoptosis. Cancer Res., 69 (17): 6969-77. [PMID:19690138]

10. Kothe M, Kohls D, Low S, Coli R, Rennie GR, Feru F, Kuhn C, Ding YH. (2007) Selectivity-determining residues in Plk1. Chem Biol Drug Des, 70 (6): 540-6. [PMID:18005335]

11. Liu S, Yosief HO, Dai L, Huang H, Dhawan G, Zhang X, Muthengi AM, Roberts J, Buckley DL, Perry JA et al.. (2018) Structure-Guided Design and Development of Potent and Selective Dual Bromodomain 4 (BRD4)/Polo-like Kinase 1 (PLK1) Inhibitors. J. Med. Chem., 61 (17): 7785-7795. [PMID:30125504]

12. Steegmaier M, Hoffmann M, Baum A, Lénárt P, Petronczki M, Krssák M, Gürtler U, Garin-Chesa P, Lieb S, Quant J et al.. (2007) BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo. Curr. Biol., 17 (4): 316-22. [PMID:17291758]

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. Zhang Q, Xia Z, Mitten MJ, Lasko LM, Klinghofer V, Bouska J, Johnson EF, Penning TD, Luo Y, Giranda VL et al.. (2012) Hit to Lead optimization of a novel class of squarate-containing polo-like kinases inhibitors. Bioorg. Med. Chem. Lett., 22 (24): 7615-22. [PMID:23103095]

15. Śledź P, Stubbs CJ, Lang S, Yang YQ, McKenzie GJ, Venkitaraman AR, Hyvönen M, Abell C. (2011) From crystal packing to molecular recognition: prediction and discovery of a binding site on the surface of polo-like kinase 1. Angew. Chem. Int. Ed. Engl., 50 (17): 4003-6. [PMID:21472932]

How to cite this page

Polo-like kinase (PLK) family: polo like kinase 1. Last modified on 04/09/2018. Accessed on 19/11/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2168.