General Information of the Protein
Protein ID
PT01023
Protein Name
Cyclin-dependent kinase 4
Secondarily
Protein Name
Cell division protein kinase 4
PSK-J3
Gene Name
CDK4
Sequence
MATSRYEPVAEIGVGAYGTVYKARDPHSGHFVALKSVRVPNGGGGGGGLPISTVREVALLRRLEAFEHPNVVRLMDVCATSRTDREIKVTLVFEHVDQDLRTYLDKAPPPGLPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGTVKLADFGLARIYSYQMALTPVVVTLWYRAPEVLLQSTYATPVDMWSVGCIFAEMFRRKPLFCGNSEADQLGKIFDLIGLPPEDDWPRDVSLPRGAFPPRGPRPVQSVVPEMEESGAQLLLEMLTFNPHKRISAFRALQHSYLHKDEGNPE
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
CMGC protein kinase group
Function
Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex.
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Uniprot ID
Primary ID:
P11802

Secondarily ID:
B2R9A0
B4DNF9
O00576
Q6FG61
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Ensembl ID
ENSG00000135446
HGNC ID
HGNC:1773
Subcellular Location
Cytoplasm
Nucleus
Nucleus membrane
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000182 , JeKo-1
 Cell Line Info 
Compound ID Compound Name Compound Formula
CP0009812
 Compound Info 
4-(5-Chloro-3-isopropyl-1H-pyrazol-4-yl)-N-(5-(piperidin-4-yl)-pyridin-2-yl)pyrimidin-2-amine
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C20H24ClN7
  2
1
IC50 = 134 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
2
IC50 = 383 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
CP0007953
 Compound Info 
4-[5-chloro-3-(1-methylethyl)-1H-pyrazol-4-yl]-N-(5-piperazin-1-ylpyridin-2-yl)pyrimidin-2-amine
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C19H23ClN8
  2
1
IC50 = 223 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
2
IC50 = 467 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
CP0004203
 Compound Info 
4-(5-Chloro-3-isopropyl-1H-pyrazol-4-yl)-N-(5-(4-(dimethylamino)piperidin-1-yl)pyridin-2-yl)pyrimidin-2-amine
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C22H29ClN8
  2
1
IC50 = 324 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
2
IC50 = 365 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
CP0007952
 Compound Info 
4-(3-Isopropyl-1H-pyrazol-4-yl)-N-(5-(piperazin-1-yl)pyridin-2-yl)pyrimidin-2-amine
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C19H24N8
  2
1
IC50 = 451 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
2
IC50 = 591 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
CP0004204
 Compound Info 
N-[5-[4-(dimethylamino)piperidin-1-yl]pyridin-2-yl]-4-[5-propan-2-yl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrimidin-2-amine
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C23H29F3N8
  2
1
IC50 = 468 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
2
IC50 = 557 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0006340
 Compound Info 
Dinaciclib
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C21H28N6O2
  2
1 IC50 = 1 nM
2 IC50 = 127 nM
CP0025156
 Compound Info 
US8623885, 5
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C26H29N7O2
  1
1 IC50 = 2.4 nM
CP0000866
 Compound Info 
6-Acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one Hydrochloride
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C24H29N7O2
  6
1 IC50 = 8.2 nM
2 IC50 = 9 nM
3 IC50 = 11 nM
4 IC50 = 16 nM
5 IC50 = 18 nM
6 IC50 < 20 nM
CP0001372
 Compound Info 
(2R,3R)-3-[2-[4-(cyclopropylsulfonimidoyl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]oxybutan-2-ol
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C18H21F3N4O3S
  1
1 IC50 = 11 nM
CP0018477
 Compound Info 
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide
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C21H16ClF3N4O3
  1
1 Kd > 10000 nM
Clinical Information about the Protein
Target 1 ( Cyclin-dependent kinase 4 (CDK4) )
Target Type Successful Target
Disease 7 Target-related Diseases  7
1 Psoriasis vulgaris [ICD-11: EA90]
2 Breast cancer [ICD-11: 2C60-2C65]
3 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
4 Mantle cell lymphoma [ICD-11: 2A85.5]
5 Small-cell lung cancer [ICD-11: 2C25.Y]
6 Advanced solid tumour [ICD-11: 2A00-2F9Z]
7 Retinoblastoma [ICD-11: 2D02.2]
Approved Drug(s) 4 Approved Drugs  4
1 Apremilast
 Drug Info 
Approved
Psoriasis vulgaris
2 LY2835219
 Drug Info 
Approved
Breast cancer
3 Palbociclib
 Drug Info 
Approved
Breast cancer
4 Trilaciclib
 Drug Info 
Approved
Small-cell lung cancer
Clinical Trial Drug(s) 9 Clinical Trial Drugs  9
1 LEE011
 Drug Info 
Phase 3
Solid tumour/cancer
2 G1T38
 Drug Info 
Phase 2
Breast cancer
3 P-276
 Drug Info 
Phase 2
Breast cancer
4 P276-00
 Drug Info 
Phase 2
Mantle cell lymphoma
5 Ro 31-7453
 Drug Info 
Phase 2
Solid tumour/cancer
6 AG-024322
 Drug Info 
Phase 1
Solid tumour/cancer
7 FN-1501
 Drug Info 
Phase 1
Solid tumour/cancer
8 P1446A-05
 Drug Info 
Phase 1
Solid tumour/cancer
9 PHA-793887
 Drug Info 
Phase 1
Solid tumour/cancer
Discontinued Drug(s) 3 Discontinued Drugs  3
1 BAY 10-00394
 Drug Info 
Discontinued in Phase 2
Small-cell lung cancer
2 R547
 Drug Info 
Discontinued in Phase 1
Advanced solid tumour
3 PD-0183812
 Drug Info 
Terminated
Retinoblastoma