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cyclin dependent kinase 4

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Target id: 1976

Nomenclature: cyclin dependent kinase 4

Abbreviated Name: CDK4

Family: CDK4 subfamily

Contents:

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 P11802 (Hs), P30285 (Mm), P35426 (Rn)
BRENDA 2.7.11.22
ChEMBL Target CHEMBL331 (Hs), CHEMBL2134 (Mm)
Ensembl Gene ENSG00000135446 (Hs), ENSMUSG00000006728 (Mm), ENSRNOG00000025602 (Rn)
Entrez Gene 1019 (Hs), 12567 (Mm), 94201 (Rn)
Human Protein Atlas ENSG00000135446 (Hs)
KEGG Enzyme 2.7.11.22
KEGG Gene hsa:1019 (Hs), mmu:12567 (Mm), rno:94201 (Rn)
OMIM 123829 (Hs)
Orphanet ORPHA119289 (Hs)
Pharos P11802 (Hs)
RefSeq Nucleotide NM_000075 (Hs), NM_009870 (Mm), NM_053593 (Rn)
RefSeq Protein NP_000066 (Hs), NP_034000 (Mm), NP_446045 (Rn)
UniProtKB P11802 (Hs), P30285 (Mm), P35426 (Rn)
Wikipedia CDK4 (Hs)
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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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]

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CDK4 subfamily: cyclin dependent kinase 4. Last modified on 13/08/2024. Accessed on 12/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1976.