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polo like kinase 1

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Target id: 2168

Nomenclature: polo like kinase 1

Abbreviated Name: PLK1

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 - 603 16p12.2 PLK1 polo like kinase 1
Mouse - 603 7 65.52 cM Plk1 polo like kinase 1
Rat - 603 1q36 Plk1 polo-like kinase 1
Previous and Unofficial Names Click here for help
STPK13 | polo-like kinase 1
Database Links Click here for help
Alphafold P53350 (Hs), Q07832 (Mm), Q62673 (Rn)
BRENDA 2.7.11.21
CATH/Gene3D 3.30.1120.30
ChEMBL Target CHEMBL3024 (Hs)
Ensembl Gene ENSG00000166851 (Hs), ENSMUSG00000030867 (Mm), ENSRNOG00000018815 (Rn)
Entrez Gene 5347 (Hs), 18817 (Mm), 25515 (Rn)
Human Protein Atlas ENSG00000166851 (Hs)
KEGG Enzyme 2.7.11.21
KEGG Gene hsa:5347 (Hs), mmu:18817 (Mm), rno:25515 (Rn)
OMIM 602098 (Hs)
Pharos P53350 (Hs)
RefSeq Nucleotide NM_005030 (Hs), NM_011121 (Mm), NM_017100 (Rn)
RefSeq Protein NP_005021 (Hs), NP_035251 (Mm), NP_058796 (Rn)
SynPHARM 79928 (in complex with BI-2536)
81115 (in complex with BI-2536)
80808 (in complex with NMS-P937)
84040 (in complex with Ro3280)
84039 (in complex with Ro3280)
80866 (in complex with volasertib)
UniProtKB P53350 (Hs), Q07832 (Mm), Q62673 (Rn)
Wikipedia PLK1 (Hs)
Selected 3D Structures Click here for help
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:  12
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:  18
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:  onvansertib
Resolution:  2.2Å
Species:  Human
References:  2
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
Ro3280 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 10.1 pKd 3
⤷ pKd 10.1 (Kd 9x10-11 M) [3]
Description: Ambit selectivity screen at 1μM Ro3280.
GSK-461364A Small molecule or natural product Primary target of this compound Hs Inhibition 9.3 pKi 9
⤷ pKi 9.3 (Ki 5x10-10 M) [9]
BI-2536 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pKi 17
⤷ pKi 8.5 (Ki 3x10-9 M) [17]
BI-2536 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.1 pIC50 14
⤷ pIC50 9.1 (IC50 8.3x10-10 M) [14]
volasertib Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 9.1 pIC50 17
⤷ pIC50 9.1 (IC50 8.7x10-10 M) [17]
onvansertib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pIC50 2
⤷ pIC50 8.7 (IC50 2x10-9 M) [2]
GSK579289A Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.7 pIC50 6
⤷ pIC50 8.7 (IC50 2x10-9 M) [6]
compound 2 [PMID: 19097784] Small molecule or natural product Hs Inhibition 8.7 pIC50 7
⤷ pIC50 8.7 (IC50 2x10-9 M) [7]
MLN0905 Small molecule or natural product Hs Inhibition 8.7 pIC50 5
⤷ pIC50 8.7 (IC50 2x10-9 M) [5]
Ro3280 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pIC50 3
⤷ pIC50 8.5 (IC50 3x10-9 M) [3]
Description: In a biochemical enzymatic assay.
GW853606 Small molecule or natural product Hs Inhibition 8.1 pIC50 7
⤷ pIC50 8.1 (IC50 9x10-9 M) [7]
compound 6 [PMID: 30125504] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 pIC50 13
⤷ pIC50 8.0 (IC50 9.9x10-9 M) [13]
Description: Biochemical inhibition of PLK1.
WNY0824 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 15
⤷ pIC50 7.7 (IC50 2.2x10-8 M) [15]
dual BRD4/PLK1 inhibitor 23 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 pIC50 13
⤷ pIC50 7.4 (IC50 4x10-8 M) [13]
Description: Biochemical inhibition of PLK1.
plogosertib Small molecule or natural product Hs Inhibition >7.0 pIC50 10
⤷ pIC50 >7.0 (IC50 <1x10-7 M) [10]
Description: This is a 'binned' IC50 value from the reference patent
XY-06-007 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.0 pIC50 11
⤷ pIC50 6.0 (IC50 9.85x10-7 M) [11]
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: 4,16
Key to terms and symbols Click column headers to sort
Target used in screen: PLK1
Ligand Sp. Type Action Value Parameter
GSK-461364A Small molecule or natural product Hs Inhibitor Inhibition 10.0 pKd
BI-2536 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.7 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.7 pKd
GSK-1838705A Small molecule or natural product Hs Inhibitor Inhibition 7.3 pKd
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.9 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.7 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.1 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand 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 Click here for help
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 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.4
JAK inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 10.5 14.0 17.0
PDK1/Akt/Flt dual pathway inhibitor Small molecule or natural product Hs Inhibitor Inhibition 28.6 103.0 64.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 36.9 48.5 6.5
compound 52 [PMID: 9677190] Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 44.1 30.0 6.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 46.2 50.0 17.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 50.2 88.0 112.0
isogranulatimide Small molecule or natural product Hs Inhibitor Inhibition 50.8 62.0 60.0
aminopurvalanol A Small molecule or natural product Hs Inhibitor Inhibition 54.9 50.0 9.0
AG 112 Small molecule or natural product Hs Inhibitor Inhibition 60.8 79.0 36.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Cellular signalling

References

Show »

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. Hollick JJ, Jones SD, Flynn CJ, Thomas MG. (2009) Pyrimidine derivatives as protein kinase inhibitors. Patent number: WO2009040556A1. Assignee: Cyclacel Limited. Priority date: 28/09/2007. Publication date: 02/04/2009.

11. Hu R, Wang WL, Yang YY, Hu XT, Wang QW, Zuo WQ, Xu Y, Feng Q, Wang NY. (2022) Identification of a selective BRD4 PROTAC with potent antiproliferative effects in AR-positive prostate cancer based on a dual BET/PLK1 inhibitor. Eur J Med Chem, 227: 113922. [PMID:34700270]

12. 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]

13. 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]

14. 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]

15. Wang NY, Xu Y, Xiao KJ, Zuo WQ, Zhu YX, Hu R, Wang WL, Shi YJ, Yu LT, Liu ZH. (2020) Design, synthesis, and biological evaluation of 4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridine derivatives as novel dual-PLK1/BRD4 inhibitors. Eur J Med Chem, 191: 112152. [PMID:32088495]

16. 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]

17. 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]

18. 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 23/08/2022. Accessed on 06/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2168.