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cyclin dependent kinase 4

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Target not currently curated in GtoImmuPdb

Target id: 1976

Nomenclature: cyclin dependent kinase 4

Abbreviated Name: CDK4

Family: CDK4 subfamily

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 303 12q14.1 CDK4 cyclin dependent kinase 4
Mouse - 303 10 D3 Cdk4 cyclin dependent kinase 4
Rat - 303 7q22 Cdk4 cyclin-dependent kinase 4
Previous and Unofficial Names Click here for help
cell division protein kinase 4 | CRK3 | p34/cdk4 | PSK-J3
Database Links Click here for help
Alphafold
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  CRYSTAL STRUCTURE OF CDK4 IN COMPLEX WITH A D-TYPE CYCLIN
PDB Id:  2W96
Resolution:  2.3Å
Species:  Human
References:  11
Enzyme Reaction Click here for help
EC Number: 2.7.11.22

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
trilaciclib Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 10.0 pKd 3
pKd 10.0 (Kd 1x10-10 M) [3]
Description: Inhibition of CDK4/cyclin D3
atirmociclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.2 pKi 8
pKi 9.2 (Ki 6x10-10 M) [8]
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 9.0 pKi 12
pKi 9.0 (Ki 1x10-9 M) [12]
Description: Assayed using CDK4/cyclin D1 complex.
PF-06873600 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.9 pKi 2
pKi 8.9 (Ki 1.37x10-9 M) [2]
Description: Evaluated in a CDK4/Cyclin D3 mobility shift assay.
ulecaciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pKi 36
pKi 8.5 (Ki 3x10-9 M) [36]
Description: Inhibition of CDK4/cyclin D1 in vitro
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 7.2 pKi 6
pKi 7.2 (Ki 6.5x10-8 M) [6]
BMS-387032 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.0 pKi 17
pKi 6.0 (Ki 9.25x10-7 M) [17]
cimpuciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.3 pIC50 25
pIC50 9.3 (IC50 4.9x10-10 M) [25]
trilaciclib Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 9.0 pIC50 3
pIC50 9.0 (IC50 1x10-9 M) [3]
Description: Inhibition of CDK4/cyclin D1
lerociclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.0 pIC50 33
pIC50 9.0 (IC50 1x10-9 M) [33]
Description: Inhibition of CDK4/cyclin D1
tibremciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 37
pIC50 8.7 (IC50 1.9x10-9 M) [37]
abemaciclib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pIC50 15
pIC50 8.7 (IC50 2x10-9 M) [15]
Description: CDK4/cyclin D1 complex expressed in and purified from insect cells. Assays used the methanesulfonate salt of the compound.
inixaciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 28
pIC50 8.7 (IC50 2x10-9 M) [28]
crozbaciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 39
pIC50 8.5 (IC50 3x10-9 M) [39]
Description: Inhibition of CDK4/cyclin D1 in vitro
narazaciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 29
pIC50 8.4 (IC50 3.9x10-9 M) [29]
Description: CDK2/CyclinD1
RGB-286638 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.4 pIC50 9
pIC50 8.4 (IC50 4x10-9 M) [9]
Description: in association with cyclin D1
Cdk4 inhibitor III Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.2 pIC50 30
pIC50 8.2 (IC50 6x10-9 M) [30]
Description: CDK4/cyclin D1 complex
ribociclib Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.0 pIC50 4
pIC50 8.0 (IC50 1x10-8 M) [4]
dalpiciclib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 8.0 pIC50 35
pIC50 8.0 (IC50 1.1x10-8 M) [35]
palbociclib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 – 8.5 pIC50 14,34-35
pIC50 8.5 (IC50 3.2x10-9 M) [34]
pIC50 8.0 (IC50 1.1x10-8 M) [14]
pIC50 7.4 (IC50 4.4x10-8 M) [35]
Ro-0505124 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.7 pIC50 13
pIC50 7.7 (IC50 2x10-8 M) [13]
BSJ-03-204 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 18
pIC50 7.6 (IC50 2.69x10-8 M) [18]
Description: Inhibition of CDK4/cyclin D1 kinase activity in a biochemical assay.
CP-10 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.5 pIC50 34
pIC50 7.5 (IC50 3x10-8 M) [34]
compound 9b [PMID: 18986805] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pIC50 19
pIC50 7.3 (IC50 5x10-8 M) [19]
BSJ-04-132 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pIC50 18
pIC50 7.3 (IC50 5.06x10-8 M) [18]
Description: Inhibition of CDK4/cyclin D1 kinase activity in a biochemical assay.
riviciclib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.2 pIC50 22
pIC50 7.2 (IC50 6.3x10-8 M) [22]
Description: CDK4/cyclin D1 complex
Cdk4 inhibitor Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.1 pIC50 40
pIC50 7.1 (IC50 7.6x10-8 M) [40]
Description: CDK4/cyclin D1 complex
voruciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 26
pIC50 7.1 (IC50 9x10-8 M) [26]
Description: Inhibition of CDK4/cyclinD1.
AT-7519 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 pIC50 32
pIC50 7.0 (IC50 1x10-7 M) [32]
BSJ-03-123 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.0 pIC50 18
pIC50 7.0 (IC50 1.06x10-7 M) [18]
Description: Inhibition of CDK4/cyclin D1 activity in a biochemical kinase assay.
milciclib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.7 – 6.8 pIC50 5,21
pIC50 6.8 (IC50 1.6x10-7 M) [5]
Description: CDK4/cyclin D1 complex
pIC50 6.7 (IC50 2.2x10-7 M) [21]
Description: In vitro inhibition of CDK4/cyclin D.
Cdk4 inhibitor II Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.7 pIC50 23
pIC50 6.7 (IC50 2x10-7 M) [23]
Description: CDK4/cyclin D1 complex used in assay
tanuxiciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.5 pIC50 7
pIC50 6.5 (IC50 3.415x10-7 M) [7]
Description: CDK3/cyclinD
fascaplysin Small molecule or natural product Primary target of this compound Hs Inhibition 6.5 pIC50 31
pIC50 6.5 (IC50 3.5x10-7 M) [31]
Description: CDK4/cyclin D1 complex
SU9516 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.8 – 6.7 pIC50 21,24
pIC50 6.7 (IC50 2x10-7 M) [24]
Description: CDK4/cyclin D1 complex used in assay
pIC50 5.8 (IC50 1.7x10-6 M) [21]
Description: In vitro inhibition of CDK4/cyclin D.
CDK inhibitor 4.35 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 pIC50 20
pIC50 6.2 (IC50 6.03x10-7 M) [20]
Description: Inhibition of CDK4/cyclin D1 complex.
purvalanol A Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.1 pIC50 16
pIC50 6.1 (IC50 8.5x10-7 M) [16]
Description: CDK4/cyclin D1 complex used in assay
CGP74514A Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.5 pIC50 21
pIC50 5.5 (IC50 3x10-6 M) [21]
Description: In vitro inhibition of human CDK4/cyclin D.
Cdk2 inhibitor IV Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.3 pIC50 27
pIC50 5.3 (IC50 5.5x10-6 M) [27]
Description: CDK4/cyclin D complex used in assay
purvalanol B Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition <5.0 pIC50 16
pIC50 <5.0 (IC50 >1x10-5 M) [16]
Description: CDK4/cyclin D1 complex used in assay
Inhibitor Comments
Fascaplysin did not inhibit CDK4/cyclin D2 and CDK4/cyclin D3 at concentrations >100μM, but did inhibit CDK6/cyclin D2 but with a low affinity of 35000nM [31].
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: 10,38

Key to terms and symbols Click column headers to sort
Target used in screen: CDK4-cyclinD1
Ligand Sp. Type Action Value Parameter
R547 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.2 pKd
alvocidib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
AT-7519 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.7 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.3 pKd
BMS-387032 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.1 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 5.9 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 5.9 pKd
Target used in screen: CDK4-cyclinD3
Ligand Sp. Type Action Value Parameter
R547 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.1 pKd
alvocidib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.5 pKd
AT-7519 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.9 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.7 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 pKd
BMS-387032 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
PHA-665752 Small molecule or natural product Hs Inhibitor Inhibition 6.4 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.2 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

Key to terms and symbols Click column headers to sort
Target used in screen: nd/CDK4/cyclin D1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Small molecule or natural product Hs Inhibitor Inhibition 2.9
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.2
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 11.2
alsterpaullone 2-cyanoethyl Small molecule or natural product Hs Inhibitor Inhibition 11.8
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 14.0
JNJ-7706621 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 20.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 27.5
SU9516 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 33.7
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 35.3
Target used in screen: nd/CDK4/cyclin D3
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Small molecule or natural product Hs Inhibitor Inhibition 3.4
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.7
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.3
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 16.0
Cdk4 inhibitor Small molecule or natural product Hs Inhibitor Inhibition 21.1
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 21.3
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 22.2
alsterpaullone 2-cyanoethyl Small molecule or natural product Hs Inhibitor Inhibition 25.9
JNJ-7706621 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 34.7
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 44.5
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Dedifferentiated liposarcoma
Synonyms: Liposarcoma [Disease Ontology: DOID:3382]
Disease Ontology: DOID:3382
Orphanet: ORPHA99970
Disease:  Melanoma, cutaneous malignant, susceptibility to, 3; CMM3
Synonyms: Familial melanoma [Orphanet: ORPHA618]
OMIM: 609048
Orphanet: ORPHA618
Disease:  Well-differentiated liposarcoma
Synonyms: Liposarcoma [Disease Ontology: DOID:3382]
Disease Ontology: DOID:3382
Orphanet: ORPHA99971

References

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2. 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.

3. 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]

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6. 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]

7. 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.

8. Chen P, Cho-Schultz S, Deal JG, Gallego GM, Jalaie M, Kania RS, Nair SK, Ninlovic S, Orr STM, Palmer CL. (2020) Cyclin dependent kinase inhibitors. Patent number: US20200354350A1. Assignee: Pfizer Inc. Priority date: 29/07/2020. Publication date: 12/11/2020.

9. 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]

10. 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]

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12. 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]

13. Ding Q, Gillespie P, Kim K, McComas WW, Perrotta A. (2006) Diaminothiazoles having antiproliferative activity. Patent number: US7094896. Assignee: Hoffmann-La Roche Inc.. Priority date: 22/12/2001. Publication date: 22/08/2006.

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18. Jiang B, Wang ES, Donovan KA, Liang Y, Fischer ES, Zhang T, Gray NS. (2019) Development of Dual and Selective Degraders of Cyclin-Dependent Kinases 4 and 6. Angew Chem Int Ed Engl, 58 (19): 6321-6326. [PMID:30802347]

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26. 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]

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CDK4 subfamily: cyclin dependent kinase 4. Last modified on 13/08/2024. Accessed on 08/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1976.