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cyclin dependent kinase 2

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Target not currently curated in GtoImmuPdb

Target id: 1973

Nomenclature: cyclin dependent kinase 2

Abbreviated Name: CDK2

Family: CDK1 subfamily

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 298 12q13.2 CDK2 cyclin dependent kinase 2
Mouse - 346 10 D3 Cdk2 cyclin dependent kinase 2
Rat - 298 7q11 Cdk2 cyclin dependent kinase 2
Previous and Unofficial Names Click here for help
cell division protein kinase 2
Database Links Click here for help
Alphafold
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
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:  54
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:  6
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:  8
Image of receptor 3D structure from RCSB PDB
Description:  Discovery of (4-Pyrazolyl)-2-Aminopyrimidines as Potent and Selective Inhibitors of Cyclin-Dependent Kinase 2
PDB Id:  8UV0
Ligand:  compound 17 [PMID: 38325398]
Resolution:  1.55Å
Species:  Human
References:  25
Enzyme Reaction Click here for help
EC Number: 2.7.11.22

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
R547 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.3 pKd 14
pKd 9.3 (Kd 5.3x10-10 M) [14]
AT-7519 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - 7.5 pKd 14
pKd 7.5 (Kd 3x10-8 M) [14]
BMS-387032 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.2 pKd 14
pKd 7.2 (Kd 6.9x10-8 M) [14]
PF-06873600 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.9 pKi 5
pKi 9.9 (Ki 1.2x10-10 M) [5]
Description: Evaluated in a CDK2/Cyclin E1 mobility shift assay.
aloisine Small molecule or natural product Primary target of this compound Click here for species-specific activity table 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 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 16
pKi 8.5 (Ki 3x10-9 M) [16]
Description: Assayed using CDK2/cyclin E complex.
asnuciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pKi 44
pKi 8.5 (Ki 3x10-9 M) [44]
Description: Inhibition of human recombinant His6 tagged CDK2/Cyclin A expressed in Sf21 insect cells
BMS-387032 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pKi 24
pKi 7.4 (Ki 3.8x10-8 M) [24]
seliciclib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 pKi 24
pKi 6.6 (Ki 2.5x10-7 M) [24]
Description: CDK2/cyclin A complex used in assay
VTX-11e Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.1 pKi 4
pKi 6.1 (Ki 8.52x10-7 M) [4]
compound 17 [PMID: 38325398] Small molecule or natural product Ligand has a PDB structure Hs Inhibition 9.5 pIC50 25
pIC50 9.5 (IC50 2.9x10-10 M) [25]
QR-6401 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.4 pIC50 55
pIC50 9.4 (IC50 3.7x10-10 M) [55]
Description: Inhibition of CDK2/cyclin E1
Cdk1/2 inhibitor III Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.3 pIC50 32
pIC50 9.3 (IC50 5x10-10 M) [32]
Description: CDK2/cyclin A complex
tanuxiciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.1 pIC50 11
pIC50 9.1 (IC50 9x10-10 M) [11]
Description: CDK2/cyclinE
compound 9b [PMID: 18986805] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition >9.0 pIC50 26
pIC50 >9.0 (IC50 <1x10-9 M) [26]
tagtociclib Small molecule or natural product Hs Inhibition 8.9 pIC50 46
pIC50 8.9 (IC50 1.16x10-9 M) [46]
Description: Inhibition of CDK2/Cyclin E
dinaciclib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.7 – 9.0 pIC50 27,35
pIC50 9.0 (IC50 1x10-9 M) [35]
pIC50 8.7 (IC50 2x10-9 M) [27]
Description: Inhibition of CDK2/cyclin E complex.
JNJ-7706621 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pIC50 32
pIC50 8.7 (IC50 2x10-9 M) [32]
Description: CDK2 in association with cyclin A
compound 5g [PMID: 36385925] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.6 pIC50 47
pIC50 8.6 (IC50 2.6x10-9 M) [47]
RGB-286638 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.5 pIC50 12
pIC50 8.5 (IC50 3x10-9 M) [12]
Description: in association with cyclin E
BS-194 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 23
pIC50 8.5 (IC50 3x10-9 M) [23]
CDK inhibitor 4.35 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 – 8.7 pIC50 27
pIC50 8.7 (IC50 2x10-9 M) [27]
Description: Inhibition of CDK2/cyclin E1 complex.
pIC50 8.2 (IC50 6x10-9 M) [27]
Description: Inhibition of CDK2/cyclin A2 complex.
compound 3 [PMID: 19097791] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.4 pIC50 50
pIC50 8.4 (IC50 4.1x10-9 M) [50]
purvalanol B Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pIC50 22
pIC50 8.2 (IC50 6x10-9 M) [22]
Description: CDK2/cyclin A complex used in assay
AZD5438 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pIC50 9
pIC50 8.2 (IC50 6x10-9 M) [9]
Description: CDK2/cyclin E complex.
zotiraciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 – 8.3 pIC50 21,52
pIC50 7.9 – 8.3 (IC50 1.3x10-8 – 5x10-9 M) [21,52]
roniciclib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.1 pIC50 34
pIC50 8.1 (IC50 9x10-9 M) [34]
Description: CDK2/cyclin E complex
BMS-265246 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.1 pIC50 49
pIC50 8.1 (IC50 9x10-9 M) [49]
AZD8421 Small molecule or natural product Hs Inhibition 7.2 – 8.1 pIC50 15
pIC50 8.1 (IC50 9x10-9 M) [15]
Description: Determined in a nanoBRET assay measuring cellular target engagement.
pIC50 7.2 (IC50 5.8x10-8 M) [15]
Description: Measuring inhibition of endogenous substrate phosphorylation in a cellular assay.
SU9516 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 – 7.7 pIC50 28,31
pIC50 7.7 (IC50 2.2x10-8 M) [31]
Description: CDK2/cyclin A complex used in assay
pIC50 7.6 (IC50 2.6x10-8 M) [28]
Description: In vitro inhibition of CDK2/cyclin E.
pIC50 7.6 (IC50 2.7x10-8 M) [28]
Description: In vitro inhibition of CDK2/cyclin A.
aminopurvalanol A Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.6 pIC50 17
pIC50 7.6 (IC50 2.8x10-8 M) [17]
Description: CDK2 in association with cyclin E
CGP74514A Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 – 7.6 pIC50 28
pIC50 7.6 (IC50 2.6x10-8 M) [28]
Description: In vitro inhibition of human CDK2/cyclin E.
pIC50 7.3 (IC50 4.6x10-8 M) [28]
Description: In vitro inhibition of human CDK2/cyclin A.
purvalanol A Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.5 pIC50 22
pIC50 7.5 (IC50 3.5x10-8 M) [22]
Description: CDK2/cyclin E complex used in assay
fadraciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 – 7.7 pIC50 45
pIC50 7.7 (IC50 2x10-8 M) [45]
Description: Inhibition of CDK2/cyclin E
pIC50 7.1 (IC50 9x10-8 M) [45]
Description: Inhibition of CDK2/cyclin A
AT-7519 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pIC50 48
pIC50 7.3 (IC50 4.7x10-8 M) [48]
THAL-SNS-032 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pIC50 38
pIC50 7.2 (IC50 6.2x10-8 M) [38]
Description: Biochemical inhibition of CDK2/cyclin A
kinase inhibitor 2 [PMID: 30199702] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pIC50 13
pIC50 7.2 (IC50 6.8x10-8 M) [13]
Description: CDK2/cyclin A
aloisine A Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.9 pIC50 37
pIC50 6.9 (IC50 1.2x10-7 M) [37]
Description: CDK2 in association with cyclin A
compound 89S [PMID: 19115845] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.9 pIC50 36
pIC50 6.9 (IC50 1.38x10-7 M) [36]
Description: CDK2/cyclin A complex
MK-8776 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pIC50 30
pIC50 6.8 (IC50 1.6x10-7 M) [30]
Description: CDK2/cyclin A complex in assay
milciclib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 – 7.3 pIC50 8,28
pIC50 7.3 (IC50 4.5x10-8 M) [8]
Description: CDK2/cyclin A complex
pIC50 7.0 (IC50 1.09x10-7 M) [28]
Description: In vitro inhibition of CDK2/cyclin A.
pIC50 6.2 (IC50 5.9x10-7 M) [28]
Description: In vitro inhibition of CDK2/cyclin E.
voruciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.7 pIC50 39
pIC50 6.7 (IC50 1.8x10-7 M) [39]
Description: Inhibition of CDK2/cyclinA
alvocidib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.4 – 7.0 pIC50 10,33
pIC50 6.4 – 7.0 (IC50 4x10-7 – 1x10-7 M) [10,33]
Cdk4 inhibitor III Small molecule or natural product Click here for species-specific activity table Hs Inhibition <6.7 pIC50 42
pIC50 <6.7 (IC50 >2x10-7 M) [42]
Description: CDK2/cyclin A complex
RO3306 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.6 – 6.7 pIC50 28
pIC50 6.7 (IC50 1.86x10-7 M) [28]
Description: In vitro inhibition of human CDK2/cyclin E.
pIC50 6.6 (IC50 2.53x10-7 M) [28]
Description: In vitro inhibition of human CDK2/cyclin A.
istisociclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pIC50 19
pIC50 6.4 (IC50 3.97x10-7 M) [19]
Description: Inhibition of CDK2/Cyclin A
Cdk2 inhibitor IV Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.4 – 6.4 pIC50 28,41
pIC50 6.4 (IC50 4x10-7 M) [28]
pIC50 6.4 (IC50 4.1x10-7 M) [41]
Description: CDK2/cyclin A complex used in assay
BX-795 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.4 pIC50 18
pIC50 6.4 (IC50 4.3x10-7 M) [18]
Cdk2 inhibitor III Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 pIC50 43
pIC50 6.3 (IC50 5x10-7 M) [43]
Description: CDK2/cyclin E complex
Cdk4 inhibitor Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 pIC50 57
pIC50 6.3 (IC50 5.2x10-7 M) [57]
Description: CDK2/cyclin E complex
bohemine Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.2 pIC50 51
pIC50 6.2 (IC50 6x10-7 M) [51]
Description: CDK2/cyclin E complexes purified from sf9 cells.
samuraciclib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 pIC50 40
pIC50 6.2 (IC50 6.2x10-7 M) [40]
Description: In a biochemical assay.
BX-912 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pIC50 18
pIC50 6.2 (IC50 6.5x10-7 M) [18]
kenpaullone Small molecule or natural product Primary target of this compound Click here for species-specific activity table Mgl Inhibition 6.2 pIC50 56
pIC50 6.2 (IC50 6.8x10-7 M) [56]
Description: CDK2/cyclin A complex
BS-181 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure 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 Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.9 pIC50 7
pIC50 5.9 (IC50 1.29x10-6 M) [7]
Description: Inhibition of CDK2/cyclinA
Cdk4 inhibitor II Small molecule or natural product Click here for species-specific activity table Hs Inhibition <4.0 pIC50 29
pIC50 <4.0 (IC50 >1x10-4 M) [29]
Description: CDK2/cyclin A complex used in assay
View species-specific inhibitor tables
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: 14,53

Key to terms and symbols Click column headers to sort
Target used in screen: CDK2
Ligand Sp. Type Action Value Parameter
R547 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.3 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.7 pKd
AT-7519 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.5 pKd
BMS-387032 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.3 pKd
alvocidib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure 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 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: 2,20

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 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.3 -1.0 0.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.9 1.0 0.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.6 -2.0 -1.0
Cdk/Crk inhibitor Small molecule or natural product Hs Inhibitor Inhibition 2.0 0.0 0.0
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 2.1 1.0 0.0
JNJ-7706621 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.2 -1.0 1.0
alsterpaullone 2-cyanoethyl Small molecule or natural product Hs Inhibitor Inhibition 2.9 0.0 1.0
aminopurvalanol A Small molecule or natural product Hs Inhibitor Inhibition 4.1 34.0 4.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 4.2 1.0 0.0
purvalanol A Small molecule or natural product 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 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.1
JNJ-7706621 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1
aminopurvalanol A Small molecule or natural product Hs Inhibitor Inhibition 8.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.5
Cdk/Crk inhibitor Small molecule or natural product Hs Inhibitor Inhibition 8.6
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.9
purvalanol A Small molecule or natural product Hs Inhibitor Inhibition 9.9
alsterpaullone 2-cyanoethyl Small molecule or natural product Hs Inhibitor Inhibition 13.4
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 14.5
GSK-3 inhibitor IX Small molecule or natural product 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
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition -1.0 -2.0
Cdk/Crk inhibitor Small molecule or natural product Hs Inhibitor Inhibition -1.0 -3.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.0 -0.5
alsterpaullone 2-cyanoethyl Small molecule or natural product Hs Inhibitor Inhibition 1.0 -2.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.0 1.0
purvalanol A Small molecule or natural product Hs Inhibitor Inhibition 2.0 -1.0
JNJ-7706621 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.0 -1.0
GSK-3 inhibitor IX Small molecule or natural product Hs Inhibitor Inhibition 3.0 7.0
CGP74514A Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.0 -1.0
K-252a Small molecule or natural product 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. Behenna DC, Chen P, Freeman-Cook KD, Hoffman RL, Jalaie M, Nagata A, Nair SK, Ninkovic S, Ornelas MA, Palmer CL et al.. (2018) Pyridopyrimdinone cdk2/4/6 inhibitors. Patent number: WO2018033815A1. Assignee: Pfizer Inc.. Priority date: 15/08/2016. Publication date: 22/02/2018.

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. Changhee M, Oh B-g, Kim Y-e, Park C-m. (2016) Heterocyclic compound and pharmaceutical composition comprising same. Patent number: WO2016126085A2. Assignee: Beyond Bio. Priority date: 04/02/2015. Publication date: 03/11/2016.

12. 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]

13. 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]

14. 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]

15. Denz CR, Grondine M, Fan J, Hsu JHR, Jackson A, Robinson J, Guo G, Li W, Wang Y, San Martin M et al.. (2024) Abstract 5730: Targeting the cell cycle with AZD8421, a potent and highly selective CDK2 inhibitor. Cancer Research, 84 (6_Supplement). DOI: 10.1158/1538-7445.AM2024-5730

16. 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]

17. 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 USA, 104 (51): 20523-8. [PMID:18077363]

18. 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]

19. Freeman DB, Hopkins TD, Mikochik PJ, Vacca JP, Gao H, Naylor-Olsen A, Rudra S, Li H, Pop MS, Villagomez RA et al.. (2023) Discovery of KB-0742, a Potent, Selective, Orally Bioavailable Small Molecule Inhibitor of CDK9 for MYC-Dependent Cancers. J Med Chem, 66 (23): 15629-15647. [PMID:37967851]

20. 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]

21. 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]

22. 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]

23. 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]

24. 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]

25. Hummel JR, Xiao KJ, Yang JC, Epling LB, Mukai K, Ye Q, Xu M, Qian D, Huo L, Weber M et al.. (2024) Discovery of (4-Pyrazolyl)-2-aminopyrimidines as Potent and Selective Inhibitors of Cyclin-Dependent Kinase 2. J Med Chem, 67 (4): 3112-3126. [PMID:38325398]

26. 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]

27. 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]

28. 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]

29. 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]

30. 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]

31. 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]

32. 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]

33. 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]

34. 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]

35. 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]

36. 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]

37. 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]

38. 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]

39. 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]

40. 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]

41. 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]

42. 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]

43. 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. Bioorg Med Chem Lett, 7 (21): 2697-2702.

44. Shao H, Shi S, Huang S, Hole AJ, Abbas AY, Baumli S, Liu X, Lam F, Foley DW, Fischer PM et al.. (2013) Substituted 4-(thiazol-5-yl)-2-(phenylamino)pyrimidines are highly active CDK9 inhibitors: synthesis, X-ray crystal structures, structure-activity relationship, and anticancer activities. J Med Chem, 56 (3): 640-59. [PMID:23301767]

45. Sheldrake PW, Atrash B, Green S, Mcdonald E, Frame S. (2008) 2, 6, 9-substituted purine derivatives having anti proliferative properties. Patent number: WO2008122767A2. Assignee: Cyclacel Limited, Cancer Research Technology Limited. Priority date: 04/04/2007. Publication date: 16/10/2008.

46. Shi Z, Tian L, Qiang T, Li J, Xing Y, Ren X, Liu C, Liang C. (2022) From Structure Modification to Drug Launch: A Systematic Review of the Ongoing Development of Cyclin-Dependent Kinase Inhibitors for Multiple Cancer Therapy. J Med Chem, 65 (9): 6390-6418. [PMID:35485642]

47. Sokolsky A, Winterton S, Kennedy K, Drake K, Stump K, Huo L, Lo Y, Ye M, Covington M, Diamond S et al.. (2022) Discovery of 5,7-Dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-ones as Highly Selective CDK2 Inhibitors. ACS Med Chem Lett, 13 (11): 1797-1804. [PMID:36385925]

48. 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]

49. 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]

50. 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]

51. 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]

52. 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]

53. 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]

54. 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]

55. Yu Y, Huang J, He H, Han J, Ye G, Xu T, Sun X, Chen X, Ren X, Li C et al.. (2023) Accelerated Discovery of Macrocyclic CDK2 Inhibitor QR-6401 by Generative Models and Structure-Based Drug Design. ACS Med Chem Lett, 14 (3): 297-304. [PMID:36923916]

56. 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]

57. 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]

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CDK1 subfamily: cyclin dependent kinase 2. Last modified on 23/05/2024. Accessed on 09/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1973.