cyclin dependent kinase 2 | CDK1 subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

Top ▲

cyclin dependent kinase 2

Target not currently curated in GtoImmuPdb

Target id: 1973

Nomenclature: cyclin dependent kinase 2

Abbreviated Name: CDK2

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

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 298 12q13 CDK2 cyclin dependent kinase 2
Mouse - 298 10 D3 Cdk2 cyclin-dependent kinase 2
Rat - 298 7q11 Cdk2 cyclin dependent kinase 2
Previous and Unofficial Names
cell division protein kinase 2
Database Links
BRENDA
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:  APO STRUCTURE OF HUMAN CYCLIN-DEPENDENT KINASE 2
PDB Id:  1PW2
Resolution:  1.95Å
Species:  Human
References:  44
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human CDK2 in complex with the inhibitor SU9516.
PDB Id:  3PY0
Ligand:  SU9516
Resolution:  1.75Å
Species:  Human
References:  5
Image of receptor 3D structure from RCSB PDB
Description:  X-ray structure of CDK2/cyclin A complex with the kinase inhibitor PHA-848125 (milciclib).
PDB Id:  2wih
Ligand:  milciclib
Resolution:  2.5Å
Species:  Human
References:  7
Enzyme Reaction
EC Number: 2.7.11.22

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 Parameter Reference
R547 Hs Inhibition 9.3 pKd 12
pKd 9.3 (Kd 5.3x10-10 M) [12]
AT-7519 Hs - 7.5 pKd 12
pKd 7.5 (Kd 3x10-8 M) [12]
BMS-387032 Hs Inhibition 7.2 pKd 12
pKd 7.2 (Kd 6.9x10-8 M) [12]
aloisine Hs Inhibition 9.3 pKi 3
pKi 9.3 (Ki 5.3x10-10 M) [3]
Description: Measuring inhibition of CDK2 in association with cyclin E
R547 Hs Inhibition 8.5 pKi 13
pKi 8.5 (Ki 3x10-9 M) [13]
Description: Assayed using CDK2/cyclin E complex.
seliciclib Hs Inhibition 6.6 pKi 20
pKi 6.6 (Ki 2.5x10-7 M) [20]
Description: CDK2/cyclin A complex used in assay
VTX-11e Hs Inhibition 6.1 pKi 4
pKi 6.1 (Ki 8.52x10-7 M) [4]
Cdk1/2 inhibitor III Hs Inhibition 9.3 pIC50 27
pIC50 9.3 (IC50 5x10-10 M) [27]
Description: CDK2/cyclin A complex
compound 9b [PMID: 18986805] Hs Inhibition >9.0 pIC50 21
pIC50 >9.0 (IC50 <1x10-9 M) [21]
dinaciclib Hs Inhibition 8.7 – 9.0 pIC50 22,30
pIC50 9.0 (IC50 1x10-9 M) [30]
pIC50 8.7 (IC50 2x10-9 M) [22]
Description: Inhibition of CDK2/cyclin E complex.
JNJ-7706621 Hs Inhibition 8.7 pIC50 27
pIC50 8.7 (IC50 2x10-9 M) [27]
Description: CDK2 in association with cyclin A
RGB-286638 Hs Inhibition 8.5 pIC50 10
pIC50 8.5 (IC50 3x10-9 M) [10]
Description: in association with cyclin E
BS-194 Hs Inhibition 8.5 pIC50 19
pIC50 8.5 (IC50 3x10-9 M) [19]
CDK inhibitor 4.35 Hs Inhibition 8.2 – 8.7 pIC50 22
pIC50 8.7 (IC50 2x10-9 M) [22]
Description: Inhibition of CDK2/cyclin E1 complex.
pIC50 8.2 (IC50 6x10-9 M) [22]
Description: Inhibition of CDK2/cyclin A2 complex.
compound 3 [PMID: 19097791] Hs Inhibition 8.4 pIC50 40
pIC50 8.4 (IC50 4.1x10-9 M) [40]
purvalanol B Hs Inhibition 8.2 pIC50 18
pIC50 8.2 (IC50 6x10-9 M) [18]
Description: CDK2/cyclin A complex used in assay
AZD5438 Hs Inhibition 8.2 pIC50 8
pIC50 8.2 (IC50 6x10-9 M) [8]
Description: CDK2/cyclin E complex.
TG02 Hs Inhibition 7.9 – 8.3 pIC50 17,42
pIC50 7.9 – 8.3 (IC50 1.3x10-8 – 5x10-9 M) [17,42]
roniciclib Hs Inhibition 8.1 pIC50 29
pIC50 8.1 (IC50 9x10-9 M) [29]
Description: CDK2/cyclin E complex
BMS-265246 Hs Inhibition 8.1 pIC50 39
pIC50 8.1 (IC50 9x10-9 M) [39]
SU9516 Hs Inhibition 7.6 – 7.7 pIC50 23,26
pIC50 7.7 (IC50 2.2x10-8 M) [26]
Description: CDK2/cyclin A complex used in assay
pIC50 7.6 (IC50 2.6x10-8 M) [23]
Description: In vitro inhibition of CDK2/cyclin E.
pIC50 7.6 (IC50 2.7x10-8 M) [23]
Description: In vitro inhibition of CDK2/cyclin A.
aminopurvalanol A Hs Inhibition 7.6 pIC50 14
pIC50 7.6 (IC50 2.8x10-8 M) [14]
Description: CDK2 in association with cyclin E
CGP74514A Hs Inhibition 7.3 – 7.6 pIC50 23
pIC50 7.6 (IC50 2.6x10-8 M) [23]
Description: In vitro inhibition of human CDK2/cyclin E.
pIC50 7.3 (IC50 4.6x10-8 M) [23]
Description: In vitro inhibition of human CDK2/cyclin A.
purvalanol A Hs Inhibition 7.5 pIC50 18
pIC50 7.5 (IC50 3.5x10-8 M) [18]
Description: CDK2/cyclin E complex used in assay
AT-7519 Hs Inhibition 7.3 pIC50 38
pIC50 7.3 (IC50 4.7x10-8 M) [38]
kinase inhibitor 2 [PMID: 30199702] Hs Inhibition 7.2 pIC50 11
pIC50 7.2 (IC50 6.8x10-8 M) [11]
Description: CDK2/cyclin A
aloisine A Hs Inhibition 6.9 pIC50 32
pIC50 6.9 (IC50 1.2x10-7 M) [32]
Description: CDK2 in association with cyclin A
compound 89S [PMID: 19115845] Hs Inhibition 6.9 pIC50 31
pIC50 6.9 (IC50 1.38x10-7 M) [31]
Description: CDK2/cyclin A complex
MK-8776 Hs Inhibition 6.8 pIC50 25
pIC50 6.8 (IC50 1.6x10-7 M) [25]
Description: CDK2/cyclin A complex in assay
milciclib Hs Inhibition 6.2 – 7.3 pIC50 7,23
pIC50 7.3 (IC50 4.5x10-8 M) [7]
Description: CDK2/cyclin A complex
pIC50 7.0 (IC50 1.09x10-7 M) [23]
Description: In vitro inhibition of CDK2/cyclin A.
pIC50 6.2 (IC50 5.9x10-7 M) [23]
Description: In vitro inhibition of CDK2/cyclin E.
voruciclib Hs Inhibition 6.7 pIC50 33
pIC50 6.7 (IC50 1.8x10-7 M) [33]
Description: Inhibition of CDK2/cyclinA
alvocidib Hs Inhibition 6.4 – 7.0 pIC50 9,28
pIC50 6.4 – 7.0 (IC50 4x10-7 – 1x10-7 M) [9,28]
Cdk4 inhibitor III Hs Inhibition <6.7 pIC50 36
pIC50 <6.7 (IC50 >2x10-7 M) [36]
Description: CDK2/cyclin A complex
RO3306 Hs Inhibition 6.6 – 6.7 pIC50 23
pIC50 6.7 (IC50 1.86x10-7 M) [23]
Description: In vitro inhibition of human CDK2/cyclin E.
pIC50 6.6 (IC50 2.53x10-7 M) [23]
Description: In vitro inhibition of human CDK2/cyclin A.
Cdk2 inhibitor IV Hs Inhibition 6.4 – 6.4 pIC50 23,35
pIC50 6.4 (IC50 4x10-7 M) [23]
pIC50 6.4 (IC50 4.1x10-7 M) [35]
Description: CDK2/cyclin A complex used in assay
BX-795 Hs Inhibition 6.4 pIC50 15
pIC50 6.4 (IC50 4.3x10-7 M) [15]
Cdk2 inhibitor III Hs Inhibition 6.3 pIC50 37
pIC50 6.3 (IC50 5x10-7 M) [37]
Description: CDK2/cyclin E complex
Cdk4 inhibitor Hs Inhibition 6.3 pIC50 46
pIC50 6.3 (IC50 5.2x10-7 M) [46]
Description: CDK2/cyclin E complex
bohemine Hs Inhibition 6.2 pIC50 41
pIC50 6.2 (IC50 6x10-7 M) [41]
Description: CDK2/cyclin E complexes purified from sf9 cells.
ICEC0942 Hs Inhibition 6.2 pIC50 34
pIC50 6.2 (IC50 6.2x10-7 M) [34]
Description: In a biochemical assay.
BX-912 Hs Inhibition 6.2 pIC50 15
pIC50 6.2 (IC50 6.5x10-7 M) [15]
kenpaullone Mgl Inhibition 6.2 pIC50 45
pIC50 6.2 (IC50 6.8x10-7 M) [45]
Description: CDK2/cyclin A complex
BS-181 Hs Inhibition 6.1 pIC50 1
pIC50 6.1 (IC50 8.8x10-7 M) [1]
Description: Evaluated using purified recombinant CDK2/cycE complex and measuring free ATP remaining in the reaction using a luciferase assay.
trilaciclib Hs Inhibition 5.9 pIC50 6
pIC50 5.9 (IC50 1.29x10-6 M) [6]
Description: Inhibition of CDK2/cyclinA
Cdk4 inhibitor II Hs Inhibition <4.0 pIC50 24
pIC50 <4.0 (IC50 >1x10-4 M) [24]
Description: CDK2/cyclin A complex used in assay
View species-specific inhibitor tables
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: 12,43

Key to terms and symbols Click column headers to sort
Target used in screen: CDK2
Ligand Sp. Type Action Affinity Parameter
R547 Hs Inhibitor Inhibition 9.3 pKd
staurosporine Hs Inhibitor Inhibition 8.1 pKd
lestaurtinib Hs Inhibitor Inhibition 7.7 pKd
AT-7519 Hs Inhibitor Inhibition 7.5 pKd
BMS-387032 Hs Inhibitor Inhibition 7.2 pKd
AST-487 Hs Inhibitor Inhibition 6.3 pKd
alvocidib Hs Inhibitor Inhibition 6.3 pKd
SB203580 Hs Inhibitor Inhibition <5.5 pKd
ruboxistaurin Hs Inhibitor Inhibition <5.5 pKd
erlotinib Hs Inhibitor Inhibition <5.5 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: 2,16

Key to terms and symbols Click column headers to sort
Target used in screen: CDK2-cyclin A/CDK2-cyclin A
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 0.3 -1.0 0.0
PKR inhibitor Hs Inhibitor Inhibition 0.9 1.0 0.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 1.6 -2.0 -1.0
Cdk/Crk inhibitor Hs Inhibitor Inhibition 2.0 0.0 0.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 2.1 1.0 0.0
JNJ-7706621 Hs Inhibitor Inhibition 2.2 -1.0 1.0
alsterpaullone 2-cyanoethyl Hs Inhibitor Inhibition 2.9 0.0 1.0
aminopurvalanol A Hs Inhibitor Inhibition 4.1 34.0 4.0
K-252a Hs Inhibitor Inhibition 4.2 1.0 0.0
purvalanol A Hs Inhibitor Inhibition 6.9 3.0 0.0
Target used in screen: CDK2/cyclin E
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
PKR inhibitor Hs Inhibitor Inhibition 4.1
JNJ-7706621 Hs Inhibitor Inhibition 7.1
aminopurvalanol A Hs Inhibitor Inhibition 8.0
staurosporine Hs Inhibitor Inhibition 8.5
Cdk/Crk inhibitor Hs Inhibitor Inhibition 8.6
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 8.9
purvalanol A Hs Inhibitor Inhibition 9.9
alsterpaullone 2-cyanoethyl Hs Inhibitor Inhibition 13.4
JAK3 inhibitor VI Hs Inhibitor Inhibition 14.5
GSK-3 inhibitor IX Hs Inhibitor Inhibition 15.4
Target used in screen: CDK2/cyclinE
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
Cdk/Crk inhibitor Hs Inhibitor Inhibition -1.0 -3.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition -1.0 -2.0
alsterpaullone 2-cyanoethyl Hs Inhibitor Inhibition 1.0 -2.0
staurosporine Hs Inhibitor Inhibition 1.0 -0.5
PKR inhibitor Hs Inhibitor Inhibition 2.0 1.0
purvalanol A Hs Inhibitor Inhibition 2.0 -1.0
JNJ-7706621 Hs Inhibitor Inhibition 2.0 -1.0
GSK-3 inhibitor IX Hs Inhibitor Inhibition 3.0 7.0
CGP74514A Hs Inhibitor Inhibition 4.0 -1.0
K-252a Hs Inhibitor Inhibition 6.0 0.0
Displaying the top 10 most potent ligands  View all ligands in screen »

References

Show »

1. Ali S, Heathcote DA, Kroll SH, Jogalekar AS, Scheiper B, Patel H, Brackow J, Siwicka A, Fuchter MJ, Periyasamy M et al.. (2009) The development of a selective cyclin-dependent kinase inhibitor that shows antitumor activity. Cancer Res., 69 (15): 6208-15. [PMID:19638587]

2. 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]

3. Anderson PC, De Sapio V, Turner KB, Elmer SP, Roe DC, Schoeniger JS. (2012) Identification of binding specificity-determining features in protein families. J. Med. Chem., 55 (5): 1926-39. [PMID:22289061]

4. Aronov AM, Tang Q, Martinez-Botella G, Bemis GW, Cao J, Chen G, Ewing NP, Ford PJ, Germann UA, Green J et al.. (2009) Structure-guided design of potent and selective pyrimidylpyrrole inhibitors of extracellular signal-regulated kinase (ERK) using conformational control. J. Med. Chem., 52 (20): 6362-8. [PMID:19827834]

5. Betzi S, Alam R, Martin M, Lubbers DJ, Han H, Jakkaraj SR, Georg GI, Schönbrunn E. (2011) Discovery of a potential allosteric ligand binding site in CDK2. ACS Chem. Biol., 6 (5): 492-501. [PMID:21291269]

6. Bisi JE, Sorrentino JA, Roberts PJ, Tavares FX, Strum JC. (2016) Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression. Mol. Cancer Ther., 15 (5): 783-93. [PMID:26826116]

7. Brasca MG, Amboldi N, Ballinari D, Cameron A, Casale E, Cervi G, Colombo M, Colotta F, Croci V, D'Alessio R et al.. (2009) Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J. Med. Chem., 52 (16): 5152-63. [PMID:19603809]

8. 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]

9. Carlson BA, Dubay MM, Sausville EA, Brizuela L, Worland PJ. (1996) Flavopiridol induces G1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells. Cancer Res., 56 (13): 2973-8. [PMID:8674031]

10. 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]

11. 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]

12. 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]

13. 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]

14. 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]

15. Feldman RI, Wu JM, Polokoff MA, Kochanny MJ, Dinter H, Zhu D, Biroc SL, Alicke B, Bryant J, Yuan S et al.. (2005) Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J. Biol. Chem., 280 (20): 19867-74. [PMID:15772071]

16. 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]

17. 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]

18. 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]

19. 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]

20. 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]

21. 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]

22. Jorda R, Havlicek L, Sturc A, Tuskova D, Daumova L, Alam M, Skerlova J, Nekardova M, Perina M, Pospíšil T et al.. (2019) 3,5,7-Substituted pyrazolo[4,3-d]pyrimidine inhibitors of cyclindependent kinases and their evaluation in lymphoma models. Journal of Medicinal Chemistry, Just Accepted Manuscript. DOI: 10.1021/acs.jmedchem.9b00189

23. 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]

24. Kubo A, Nakagawa K, Varma RK, Conrad NK, Cheng JQ, Lee WC, Testa JR, Johnson BE, Kaye FJ, Kelley MJ. (1999) The p16 status of tumor cell lines identifies small molecule inhibitors specific for cyclin-dependent kinase 4. Clin. Cancer Res., 5 (12): 4279-86. [PMID:10632371]

25. Labroli M, Paruch K, Dwyer MP, Alvarez C, Keertikar K, Poker C, Rossman R, Duca JS, Fischmann TO, Madison V et al.. (2011) Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: a template-based approach--part 2. Bioorg. Med. Chem. Lett., 21 (1): 471-4. [PMID:21094607]

26. 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]

27. 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]

28. Losiewicz MD, Carlson BA, Kaur G, Sausville EA, Worland PJ. (1994) Potent inhibition of CDC2 kinase activity by the flavonoid L86-8275. Biochem. Biophys. Res. Commun., 201 (2): 589-95. [PMID:8002990]

29. 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]

30. 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]

31. Menichincheri M, Bargiotti A, Berthelsen J, Bertrand JA, Bossi R, Ciavolella A, Cirla A, Cristiani C, Croci V, D'Alessio R et al.. (2009) First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active antitumor agents. 2. Lead discovery. J. Med. Chem., 52 (2): 293-307. [PMID:19115845]

32. Mettey Y, Gompel M, Thomas V, Garnier M, Leost M, Ceballos-Picot I, Noble M, Endicott J, Vierfond JM, Meijer L. (2003) Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. J. Med. Chem., 46 (2): 222-36. [PMID:12519061]

33. Paiva C, Godbersen JC, Soderquist RS, Rowland T, Kilmarx S, Spurgeon SE, Brown JR, Srinivasa SP, Danilov AV. (2015) Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells. PLoS ONE, 10 (11): e0143685. [PMID:26606677]

34. Patel H, Periyasamy M, Sava GP, Bondke A, Slafer BW, Kroll SHB, Barbazanges M, Starkey R, Ottaviani S, Harrod A et al.. (2018) ICEC0942, an Orally Bioavailable Selective Inhibitor of CDK7 for Cancer Treatment. Mol. Cancer Ther., 17 (6): 1156-1166. [PMID:29545334]

35. Pennati M, Campbell AJ, Curto M, Binda M, Cheng Y, Wang LZ, Curtin N, Golding BT, Griffin RJ, Hardcastle IR et al.. (2005) Potentiation of paclitaxel-induced apoptosis by the novel cyclin-dependent kinase inhibitor NU6140: a possible role for survivin down-regulation. Mol. Cancer Ther., 4 (9): 1328-37. [PMID:16170024]

36. Ryu CK, Kang HY, Lee SK, Nam KA, Hong CY, Ko WG, Lee BH. (2000) 5-Arylamino-2-methyl-4,7-dioxobenzothiazoles as inhibitors of cyclin-dependent kinase 4 and cytotoxic agents. Bioorg. Med. Chem. Lett., 10 (5): 461-4. [PMID:10743948]

37. Schow SR, Mackman RL, Blum CL, Brooks E, Horsma AG, Joly A, Kerwar SS, Lee G, Shiffman D, Nelson MG et al.. (1997) Synthesis and activity of 2,6,9-trisubstituted purines. Bioorganic & Medicinal Chemistry Letters, 7 (21): 2697-2702.

38. Squires MS, Feltell RE, Wallis NG, Lewis EJ, Smith DM, Cross DM, Lyons JF, Thompson NT. (2009) Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Mol. Cancer Ther., 8 (2): 324-32. [PMID:19174555]

39. Sutherland JJ, Low J, Blosser W, Dowless M, Engler TA, Stancato LF. (2011) A robust high-content imaging approach for probing the mechanism of action and phenotypic outcomes of cell-cycle modulators. Mol. Cancer Ther., 10 (2): 242-54. [PMID:21216932]

40. Trujillo JI, Kiefer JR, Huang W, Thorarensen A, Xing L, Caspers NL, Day JE, Mathis KJ, Kretzmer KK, Reitz BA et al.. (2009) 2-(6-Phenyl-1H-indazol-3-yl)-1H-benzo[d]imidazoles: design and synthesis of a potent and isoform selective PKC-zeta inhibitor. Bioorg. Med. Chem. Lett., 19 (3): 908-11. [PMID:19097791]

41. Vermeulen K, Strnad M, Krystof V, Havlícek L, Van der Aa A, Lenjou M, Nijs G, Rodrigus I, Stockman B, van Onckelen H et al.. (2002) Antiproliferative effect of plant cytokinin analogues with an inhibitory activity on cyclin-dependent kinases. Leukemia, 16 (3): 299-305. [PMID:11896531]

42. William AD, Lee AC, Goh KC, Blanchard S, Poulsen A, Teo EL, Nagaraj H, Lee CP, Wang H, Williams M et al.. (2012) Discovery of kinase spectrum selective macrocycle (16E)-14-methyl-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (SB1317/TG02), a potent inhibitor of cyclin dependent kinases (CDKs), Janus kinase 2 (JAK2), and fms-like tyrosine kinase-3 (FLT3) for the treatment of cancer. J. Med. Chem., 55 (1): 169-96. [PMID:22148278]

43. 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]

44. Wu SY, McNae I, Kontopidis G, McClue SJ, McInnes C, Stewart KJ, Wang S, Zheleva DI, Marriage H, Lane DP et al.. (2003) Discovery of a novel family of CDK inhibitors with the program LIDAEUS: structural basis for ligand-induced disordering of the activation loop. Structure, 11 (4): 399-410. [PMID:12679018]

45. Zaharevitz DW, Gussio R, Leost M, Senderowicz AM, Lahusen T, Kunick C, Meijer L, Sausville EA. (1999) Discovery and initial characterization of the paullones, a novel class of small-molecule inhibitors of cyclin-dependent kinases. Cancer Res., 59 (11): 2566-9. [PMID:10363974]

46. Zhu G, Conner SE, Zhou X, Shih C, Li T, Anderson BD, Brooks HB, Campbell RM, Considine E, Dempsey JA et al.. (2003) Synthesis, structure-activity relationship, and biological studies of indolocarbazoles as potent cyclin D1-CDK4 inhibitors. J. Med. Chem., 46 (11): 2027-30. [PMID:12747775]

How to cite this page

CDK1 subfamily: cyclin dependent kinase 2. Last modified on 18/04/2019. Accessed on 23/05/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1973.