cyclin dependent kinase 1 | CDK1 subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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cyclin dependent kinase 1

Target not currently curated in GtoImmuPdb

Target id: 1961

Nomenclature: cyclin dependent kinase 1

Abbreviated Name: CDK1

Family: CDK1 subfamily

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

Contents:

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 297 10q21.2 CDK1 cyclin dependent kinase 1
Mouse - 297 10 B5.3 Cdk1 cyclin-dependent kinase 1
Rat - 297 20p11 Cdk1 cyclin-dependent kinase 1
Previous and Unofficial Names
CDC2 | CDC28A | cell division cycle 2 homolog A | p34 protein kinase | p34
Database Links
BRENDA 2.7.11.22, 2.7.11.23
ChEMBL Target CHEMBL308 (Hs), CHEMBL4084 (Mm)
Ensembl Gene ENSG00000170312 (Hs), ENSMUSG00000019942 (Mm), ENSRNOG00000000632 (Rn)
Entrez Gene 983 (Hs), 12534 (Mm), 54237 (Rn)
Human Protein Atlas ENSG00000170312 (Hs)
KEGG Enzyme 2.7.11.22, 2.7.11.23
KEGG Gene hsa:983 (Hs), mmu:12534 (Mm), rno:54237 (Rn)
OMIM 116940 (Hs)
Pharos P06493 (Hs)
RefSeq Nucleotide NM_001170406 (Hs), NM_007659 (Mm), NM_019296 (Rn)
RefSeq Protein NP_031685 (Mm), NP_062169 (Rn)
UniProtKB P06493 (Hs), P11440 (Mm), P39951 (Rn)
Wikipedia CDK1 (Hs)
Enzyme Reaction
EC Number: 2.7.11.22
EC Number: 2.7.11.23

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
R547 Hs Inhibition 8.7 pKi 5
⤷ pKi 8.7 (Ki 2x10-9 M) [5]
Description: Assayed using CDK1/cyclin B complex.
CDK inhibitor 4.35 Hs Inhibition 7.1 pKi 15
⤷ pKi 7.1 (Ki 9x10-8 M) [15]
Description: Inhibition of CDK1/cyclin B1 complex.
BMS-387032 Hs Inhibition 6.3 pKi 11
⤷ pKi 6.3 (Ki 4.8x10-7 M) [11]
alsterpaullone 2-cyanoethyl Hs Inhibition 9.6 pIC50 6
⤷ pIC50 9.6 (IC50 2.3x10-10 M) [6]
Description: CDK1 in association with cyclin B
Cdk1/2 inhibitor III Hs Inhibition 9.2 pIC50 21
⤷ pIC50 9.2 (IC50 6x10-10 M) [21]
Description: CDK1/cyclin B complex
RGB-286638 Hs Inhibition 8.7 pIC50 3
⤷ pIC50 8.7 (IC50 2x10-9 M) [3]
Description: in association with cyclin B1
dinaciclib Hs Inhibition 8.5 pIC50 23
⤷ pIC50 8.5 (IC50 3x10-9 M) [23]
BMS-265246 Hs Inhibition 8.2 pIC50 34
⤷ pIC50 8.2 (IC50 6x10-9 M) [34]
JNJ-7706621 Hs Inhibition 8.2 pIC50 21
⤷ pIC50 8.2 (IC50 6.4x10-9 M) [21]
Description: CDK1 in association with cyclin B
roniciclib Hs Inhibition 8.1 pIC50 22
⤷ pIC50 8.1 (IC50 7x10-9 M) [22]
Description: CDK1/cyclin B complex
TG02 Hs Inhibition 8.1 pIC50 8
⤷ pIC50 8.1 (IC50 9x10-9 M) [8]
AZD5438 Hs Inhibition 7.8 pIC50 2
⤷ pIC50 7.8 (IC50 1.6x10-8 M) [2]
Description: CDK1/cyclin B1 complex.
voruciclib Hs Inhibition 7.6 pIC50 28
⤷ pIC50 7.6 (IC50 2.5x10-8 M) [28]
Description: Inhibition of CDK1/cyclinB
compound 89S [PMID: 19115845] Hs Inhibition 7.5 pIC50 25
⤷ pIC50 7.5 (IC50 3x10-8 M) [25]
Description: CDK1/cyclin B complex
aminopurvalanol A Hs Inhibition 7.5 pIC50 6
⤷ pIC50 7.5 (IC50 3.3x10-8 M) [6]
Description: CDK1 in association with cyclin B
BS-194 Hs Inhibition 7.5 pIC50 10
⤷ pIC50 7.5 (IC50 3.3x10-8 M) [10]
alsterpaullone Hs Inhibition 7.5 pIC50 20
⤷ pIC50 7.5 (IC50 3.5x10-8 M) [20]
Description: CDK1 in association with cyclin B
RO3306 Hs Inhibition 7.3 pIC50 16
⤷ pIC50 7.3 (IC50 4.7x10-8 M) [16]
Description: In vitro inhibition of human CDK1/cyclin B.
7-hydroxystaurosporine Hs Inhibition 7.3 pIC50 13
⤷ pIC50 7.3 (IC50 5x10-8 M) [13]
compound 9b [PMID: 18986805] Hs Inhibition 7.2 pIC50 14
⤷ pIC50 7.2 (IC50 6x10-8 M) [14]
CGP74514A Hs Inhibition 6.8 – 7.6 pIC50 12,16
⤷ pIC50 7.6 (IC50 2.5x10-8 M) [12]
pIC50 6.8 (IC50 1.47x10-7 M) [16]
Description: In vitro inhibition of human CDK1/cyclin B.
kinase inhibitor 2 [PMID: 30199702] Hs Inhibition 7.2 pIC50 4
⤷ pIC50 7.2 (IC50 7x10-8 M) [4]
Description: CDK1/cyclin B
riviciclib Hs Inhibition 7.1 pIC50 17
⤷ pIC50 7.1 (IC50 7.9x10-8 M) [17]
Description: CDK1/cyclin B complex
SU9516 Hs Inhibition 6.8 – 7.4 pIC50 16,19
⤷ pIC50 7.4 (IC50 4x10-8 M) [19]
Description: CDK1/cyclin B complex used in assay
pIC50 6.8 (IC50 1.68x10-7 M) [16]
Description: In vitro inhibition of CDK1/cyclin B.
aloisine A Hs Inhibition 6.8 pIC50 26
⤷ pIC50 6.8 (IC50 1.5x10-7 M) [26]
Description: CDK1 in association with cyclin B
THAL-SNS-032 Hs Inhibition 6.8 pIC50 27
⤷ pIC50 6.8 (IC50 1.71x10-7 M) [27]
Description: Biochemical inhibition of CDK1/CycB.
AT-7519 Hs Inhibition 6.7 pIC50 33
⤷ pIC50 6.7 (IC50 2.1x10-7 M) [33]
GSK-3 inhibitor IX Hs Inhibition 6.5 pIC50 24,31
⤷ pIC50 6.5 (IC50 3.2x10-7 M) [24,31]
Description: CDK1/cyclin B complex
compound 52 [PMID: 9677190] Hs Inhibition 6.5 pIC50 9
⤷ pIC50 6.5 (IC50 3.4x10-7 M) [9]
Description: CDK1/cyclin B complex
kenpaullone Mgl Inhibition 6.4 pIC50 36
⤷ pIC50 6.4 (IC50 4x10-7 M) [36]
Description: CDK1/cyclin B complex
Cdk1/5 inhibitor Hs Inhibition 6.2 pIC50 6
⤷ pIC50 6.2 (IC50 6x10-7 M) [6]
Description: CDK1/cyclin B complex
bohemine Hs Inhibition 6.0 pIC50 35
⤷ pIC50 6.0 (IC50 1.1x10-6 M) [35]
Description: CDK1/cyclin B complexes purified from sf9 cells
milciclib Hs Inhibition 5.9 pIC50 16
⤷ pIC50 5.9 (IC50 1.2x10-6 M) [16]
Description: In vitro inhibition of CDK1/cyclin B.
ICEC0942 Hs Inhibition 5.7 pIC50 29
⤷ pIC50 5.7 (IC50 1.8x10-6 M) [29]
Description: In a biochemical assay.
1-azakenpaullone Hs Inhibition 5.7 pIC50 18
⤷ pIC50 5.7 (IC50 2x10-6 M) [18]
Description: CDK1/cyclin B complex in assay
Cdk4 inhibitor Hs Inhibition 5.7 pIC50 37
⤷ pIC50 5.7 (IC50 2.1x10-6 M) [37]
Description: CDK1/cyclin B complex
Cdk2 inhibitor III Hs Inhibition 5.4 pIC50 6
⤷ pIC50 5.4 (IC50 4.2x10-6 M) [6]
Description: CDK1/cyclin B complex
Cdk1 inhibitor Hs Inhibition 5.2 pIC50 6
⤷ pIC50 5.2 (IC50 5.8x10-6 M) [6]
Description: CDK1/cyclin B complex
Cdk2 inhibitor IV Hs Inhibition 5.2 pIC50 30
⤷ pIC50 5.2 (IC50 6.6x10-6 M) [30]
Description: CDK1/cyclin B complex used in assay
CHIR-99021 Hs Inhibition 5.1 pIC50 32
⤷ pIC50 5.1 (IC50 8.8x10-6 M) [32]
View species-specific inhibitor tables
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: 1,7
Key to terms and symbols Click column headers to sort
Target used in screen: CDK1-cyclin B/CDK1-cyclin B
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
Cdk1/2 inhibitor III Hs Inhibitor Inhibition -1.8 0.0 -1.0
Cdk/Crk inhibitor Hs Inhibitor Inhibition -1.2 3.0 0.0
JNJ-7706621 Hs Inhibitor Inhibition 5.7 1.0 0.0
PKR inhibitor Hs Inhibitor Inhibition 7.8 1.0 -1.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 9.0 1.0 0.0
alsterpaullone 2-cyanoethyl Hs Inhibitor Inhibition 9.9 3.0 0.0
staurosporine Hs Inhibitor Inhibition 10.2 0.5 -0.5
CGP74514A Hs Inhibitor Inhibition 16.4 19.0 4.0
aminopurvalanol A Hs Inhibitor Inhibition 17.0 69.0 19.0
K-252a Hs Inhibitor Inhibition 18.7 5.0 -1.0
Target used in screen: nd/CDK1-cyclin A
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
Cdk1/2 inhibitor III Hs Inhibitor Inhibition -0.2
staurosporine Hs Inhibitor Inhibition 2.7
JAK3 inhibitor VI Hs Inhibitor Inhibition 6.8
PKR inhibitor Hs Inhibitor Inhibition 7.6
Cdk/Crk inhibitor Hs Inhibitor Inhibition 7.7
JNJ-7706621 Hs Inhibitor Inhibition 10.3
K-252a Hs Inhibitor Inhibition 19.8
alsterpaullone 2-cyanoethyl Hs Inhibitor Inhibition 24.8
aminopurvalanol A Hs Inhibitor Inhibition 25.9
purvalanol A Hs Inhibitor Inhibition 31.7
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Barrier integrity
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0001618 virus receptor activity IEA

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. Byth KF, Thomas A, Hughes G, Forder C, McGregor A, Geh C, Oakes S, Green C, Walker M, Newcombe N et al.. (2009) AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts. Mol. Cancer Ther., 8 (7): 1856-66. [PMID:19509270]

3. Cirstea D, Hideshima T, Santo L, Eda H, Mishima Y, Nemani N, Hu Y, Mimura N, Cottini F, Gorgun G et al.. (2013) Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia, 27 (12): 2366-75. [PMID:23807770]

4. Compain G, Oumata N, Clarhaut J, Péraudeau E, Renoux B, Galons H, Papot S. (2018) A β-glucuronidase-responsive albumin-binding prodrug for potential selective kinase inhibitor-based cancer chemotherapy. Eur J Med Chem, 158: 1-6. [PMID:30199702]

5. DePinto W, Chu XJ, Yin X, Smith M, Packman K, Goelzer P, Lovey A, Chen Y, Qian H, Hamid R et al.. (2006) In vitro and in vivo activity of R547: a potent and selective cyclin-dependent kinase inhibitor currently in phase I clinical trials. Mol. Cancer Ther., 5 (11): 2644-58. [PMID:17121911]

6. 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]

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. Goh KC, Novotny-Diermayr V, Hart S, Ong LC, Loh YK, Cheong A, Tan YC, Hu C, Jayaraman R, William AD et al.. (2012) TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti-leukemic properties. Leukemia, 26 (2): 236-43. [PMID:21860433]

9. Gray NS, Wodicka L, Thunnissen AM, Norman TC, Kwon S, Espinoza FH, Morgan DO, Barnes G, LeClerc S, Meijer L et al.. (1998) Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science, 281 (5376): 533-8. [PMID:9677190]

10. Heathcote DA, Patel H, Kroll SH, Hazel P, Periyasamy M, Alikian M, Kanneganti SK, Jogalekar AS, Scheiper B, Barbazanges M et al.. (2010) A novel pyrazolo[1,5-a]pyrimidine is a potent inhibitor of cyclin-dependent protein kinases 1, 2, and 9, which demonstrates antitumor effects in human tumor xenografts following oral administration. J. Med. Chem., 53 (24): 8508-22. [PMID:21080703]

11. Hole AJ, Baumli S, Shao H, Shi S, Huang S, Pepper C, Fischer PM, Wang S, Endicott JA, Noble ME. (2013) Comparative structural and functional studies of 4-(thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile CDK9 inhibitors suggest the basis for isotype selectivity. J. Med. Chem., 56 (3): 660-70. [PMID:23252711]

12. Imbach P, Capraro HG, Furet P, Mett H, Meyer T, Zimmermann J. (1999) 2,6,9-trisubstituted purines: optimization towards highly potent and selective CDK1 inhibitors. Bioorg. Med. Chem. Lett., 9 (1): 91-6. [PMID:9990463]

13. Jiang X, Zhao B, Britton R, Lim LY, Leong D, Sanghera JS, Zhou BB, Piers E, Andersen RJ, Roberge M. (2004) Inhibition of Chk1 by the G2 DNA damage checkpoint inhibitor isogranulatimide. Mol. Cancer Ther., 3 (10): 1221-7. [PMID:15486189]

14. Jones CD, Andrews DM, Barker AJ, Blades K, Byth KF, Finlay MR, Geh C, Green CP, Johannsen M, Walker M et al.. (2008) Imidazole pyrimidine amides as potent, orally bioavailable cyclin-dependent kinase inhibitors. Bioorg. Med. Chem. Lett., 18 (24): 6486-9. [PMID:18986805]

15. Jorda R, Havlíček L, Šturc A, Tušková D, Daumová L, Alam M, Škerlová J, Nekardová M, Peřina M, Pospíšil T et al.. (2019) 3,5,7-Substituted Pyrazolo[4,3- d]pyrimidine Inhibitors of Cyclin-Dependent Kinases and Their Evaluation in Lymphoma Models. J. Med. Chem., 62 (9): 4606-4623. DOI: 10.1021/acs.jmedchem.9b00189 [PMID:30943029]

16. Jorda R, Hendrychová D, Voller J, Řezníčková E, Gucký T, Kryštof V. (2018) How Selective Are Pharmacological Inhibitors of Cell-Cycle-Regulating Cyclin-Dependent Kinases?. J. Med. Chem., 61 (20): 9105-9120. [PMID:30234987]

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18. Kunick C, Lauenroth K, Leost M, Meijer L, Lemcke T. (2004) 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg. Med. Chem. Lett., 14 (2): 413-6. [PMID:14698171]

19. Lane ME, Yu B, Rice A, Lipson KE, Liang C, Sun L, Tang C, McMahon G, Pestell RG, Wadler S. (2001) A novel cdk2-selective inhibitor, SU9516, induces apoptosis in colon carcinoma cells. Cancer Res., 61 (16): 6170-7. [PMID:11507069]

20. Leost M, Schultz C, Link A, Wu YZ, Biernat J, Mandelkow EM, Bibb JA, Snyder GL, Greengard P, Zaharevitz DW et al.. (2000) Paullones are potent inhibitors of glycogen synthase kinase-3beta and cyclin-dependent kinase 5/p25. Eur. J. Biochem., 267 (19): 5983-94. [PMID:10998059]

21. Lin R, Connolly PJ, Huang S, Wetter SK, Lu Y, Murray WV, Emanuel SL, Gruninger RH, Fuentes-Pesquera AR, Rugg CA et al.. (2005) 1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities. J. Med. Chem., 48 (13): 4208-11. [PMID:15974571]

22. Lücking U, Jautelat R, Krüger M, Brumby T, Lienau P, Schäfer M, Briem H, Schulze J, Hillisch A, Reichel A et al.. (2013) The lab oddity prevails: discovery of pan-CDK inhibitor (R)-S-cyclopropyl-S-(4-{[4-{[(1R,2R)-2-hydroxy-1-methylpropyl]oxy}-5-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)sulfoximide (BAY 1000394) for the treatment of cancer. ChemMedChem, 8 (7): 1067-85. [PMID:23671017]

23. Martin MP, Olesen SH, Georg GI, Schönbrunn E. (2013) Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. ACS Chem. Biol., 8 (11): 2360-5. [PMID:24007471]

24. Meijer L, Skaltsounis AL, Magiatis P, Polychronopoulos P, Knockaert M, Leost M, Ryan XP, Vonica CA, Brivanlou A, Dajani R et al.. (2003) GSK-3-selective inhibitors derived from Tyrian purple indirubins. Chem. Biol., 10 (12): 1255-66. [PMID:14700633]

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27. Olson CM, Jiang B, Erb MA, Liang Y, Doctor ZM, Zhang Z, Zhang T, Kwiatkowski N, Boukhali M, Green JL et al.. (2018) Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation. Nat. Chem. Biol., 14 (2): 163-170. [PMID:29251720]

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How to cite this page

CDK1 subfamily: cyclin dependent kinase 1. Last modified on 12/11/2019. Accessed on 09/04/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1961.