General Information of the Protein
Protein ID
PT00926
Protein Name
Cyclin-dependent kinase 1
Secondarily
Protein Name
Cell division control protein 2 homolog
Cell division protein kinase 1
p34 protein kinase
Gene Name
CDK1
Secondarily
Gene Name
CDC2
CDC28A
CDKN1
P34CDC2
Sequence
MEDYTKIEKIGEGTYGVVYKGRHKTTGQVVAMKKIRLESEEEGVPSTAIREISLLKELRHPNIVSLQDVLMQDSRLYLIFEFLSMDLKKYLDSIPPGQYMDSSLVKSYLYQILQGIVFCHSRRVLHRDLKPQNLLIDDKGTIKLADFGLARAFGIPIRVYTHEVVTLWYRSPEVLLGSARYSTPVDIWSIGTIFAELATKKPLFHGDSEIDQLFRIFRALGTPNNEVWPEVESLQDYKNTFPKWKPGSLASHVKNLDENGLDLLSKMLIYDPAKRISGKMALNHPYFNDLDNQIKKM
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
CMGC protein kinase group
>
CMGC protein kinase CDK family
>
CMGC protein kinase CDC2 subfamily
Function
Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition via association with multiple interphase cyclins (PubMed:16407259, PubMed:17459720, PubMed:16933150, PubMed:18356527, PubMed:19509060, PubMed:20171170, PubMed:19917720, PubMed:20937773, PubMed:20935635, PubMed:21063390, PubMed:23355470, PubMed:23601106, PubMed:23602554, PubMed:25556658, PubMed:26829474, PubMed:30704899). Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, KAT5, LMNA, LMNB, LMNC, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MLST8, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, TPPP, UL40/R2, RAB4A, RAP1GAP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SAMHD1, SIRT2, CGAS and RUNX2 (PubMed:16407259, PubMed:17459720, PubMed:16933150, PubMed:18356527, PubMed:19509060, PubMed:20171170, PubMed:19917720, PubMed:20937773, PubMed:20935635, PubMed:21063390, PubMed:23355470, PubMed:23601106, PubMed:23602554, PubMed:25556658, PubMed:32351706, PubMed:26829474, PubMed:30704899, PubMed:34741373). CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs (PubMed:18480403, PubMed:20360007). Essential for early stages of embryonic development (PubMed:18480403, PubMed:20360007). During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation (PubMed:18480403, PubMed:20360007). Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis (PubMed:18480403, PubMed:20360007). Phosphorylates KRT5 during prometaphase and metaphase (By similarity). Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair (PubMed:20360007). Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression (PubMed:20395957). In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons (PubMed:18356527). The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis (PubMed:16371510). NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation (PubMed:19509060). In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis (PubMed:20171170). The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis (PubMed:19917720). In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis (PubMed:20937773). This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes (PubMed:20937773). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed:20935635). CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration (By similarity). CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis (PubMed:26549230). Regulates the amplitude of the cyclic expression of the core clock gene BMAL1 by phosphorylating its transcriptional repressor NR1D1, and this phosphorylation is necessary for SCF(FBXW7)-mediated ubiquitination and proteasomal degradation of NR1D1 (PubMed:27238018). Phosphorylates EML3 at 'Thr-881' which is essential for its interaction with HAUS augmin-like complex and TUBG1 (PubMed:30723163). Phosphorylates CGAS during mitosis, leading to its inhibition, thereby preventing CGAS activation by self DNA during mitosis (PubMed:32351706).
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Uniprot ID
Primary ID:
P06493

Secondarily ID:
A8K7C4
C9J497
O60764
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Ensembl ID
ENSG00000170312
HGNC ID
HGNC:1722
Subcellular Location
Nucleus
Cytoplasm
Mitochondrion
Cytoplasm
Cytoskeleton
Microtubule organizing center
Centrosome
Cytoplasm
Cytoskeleton
Spindle
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: CL000007 , HT-29
Compound ID Compound Name Compound Formula
CP0103138
4-(2-chlorophenyl)-8-(3-(dimethylamino)propoxy)-9-hydroxy-6-methylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione
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C26H24ClN3O4
 1
1
IC50 = 10 nM
   TI
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   LO
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CP0036972
4-(2-chlorophenyl)-9-hydroxy-6-methyl-8-(3-pyrrolidin-1-ylpropoxy)pyrrolo[3,4-c]carbazole-1,3-dione
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C28H26ClN3O4
 1
1
IC50 = 30 nM
   TI
   LI
   LO
   TS
CP0091753
4-(2-chlorophenyl)-9-hydroxy-6-(2-hydroxyethyl)-8-(3-pyrrolidin-1-ylpropoxy)pyrrolo[3,4-c]carbazole-1,3-dione
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C29H28ClN3O5
 1
1
IC50 = 30 nM
   TI
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   TS
CP0288607
4-(2-chlorophenyl)-9-hydroxy-8-(4-pyrrolidin-1-ylbutyl)-6H-pyrrolo[3,4-c]carbazole-1,3-dione
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C28H26ClN3O3
 1
1
IC50 = 200 nM
   TI
   LI
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   TS
CP0007420
4-(2-Chlorophenyl)-9-hydroxy-6-(3-hydroxypropyl)-pyrrolo[3,4-c]carbazole-1,3(2H,6H )-dione
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C23H17ClN2O4
 1
1
IC50 = 250 nM
   TI
   LI
   LO
   TS
CP0036892
4-(2-chlorophenyl)-8-(4-(dimethylamino)butyl)-9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione
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C26H24ClN3O3
 1
1
IC50 = 250 nM
   TI
   LI
   LO
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CP0037120
4-(2-chlorophenyl)-9-hydroxy-6-(2-hydroxyethyl)-8-(3-morpholinopropoxy)pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione
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C29H28ClN3O6
 1
1
IC50 = 250 nM
   TI
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CP0103141
4-(2-chlorophenyl)-9-hydroxy-8-(4-morpholinobutyl)pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione
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C28H26ClN3O4
 1
1
IC50 = 250 nM
   TI
   LI
   LO
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CP0288606
4-(2-chlorophenyl)-8-[3-(dimethylamino)propoxy]-9-hydroxy-6-(2-hydroxyethyl)pyrrolo[3,4-c]carbazole-1,3-dione
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C27H26ClN3O5
 1
1
IC50 = 250 nM
   TI
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CP0002311
4-(2-Chlorophenyl)-6-[3-(dimethylamino)-2-hydro-xypropyl]-9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H )-dione
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C25H22ClN3O4
 1
1
IC50 = 250 nM
   TI
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CP0004829
4-(2-chlorophenyl)-9-hydroxy-6-(2-morpholinoethyl)pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione
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C26H22ClN3O4
 1
1
IC50 = 250 nM
   TI
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CP0006410
3-(4-(2-chlorophenyl)-9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo[3,4-c]carbazol-6(1H)-yl)-N-(methylsulfonyl)propanamide
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C24H18ClN3O6S
 1
1
IC50 = 250 nM
   TI
   LI
   LO
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CP0002312
4-(2-Chlorophenyl)-9-hydroxy-6-[2-(1H-tetrazol-5-yl)-ethyl]pyrrolo[3,4-c]carbazole-1,3(2H,6H )-dione
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C23H15ClN6O3
 1
1
IC50 = 2500 nM
   TI
   LI
   LO
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CP0005464
4-(4-(2-Chlorophenyl)-9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo[3,4-c]carbazol-6(1H)-yl)butanoic acid
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C24H17ClN2O5
 1
1
IC50 > 10000 nM
   TI
   LI
   LO
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CP0008404
4-(2-Chlorophenyl)-9-hydroxy-6-[3-(1H-tetrazol-5-yl)-propyl]pyrrolo[3,4-c]carbazole-1,3(2H,6H )-dione
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C24H17ClN6O3
 1
1
IC50 > 10000 nM
   TI
   LI
   LO
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CP0013433
3-(4-(2-chlorophenyl)-9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo[3,4-c]carbazol-6(1H)-yl)propanamide
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C23H16ClN3O4
 1
1
IC50 > 10000 nM
   TI
   LI
   LO
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CP0005462
4-(2-chlorophenyl)-9-hydroxy-6-(3-(methylamino)propyl)pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione
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C24H20ClN3O3
 1
1
IC50 < 250 nM
   TI
   LI
   LO
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CP0005463
3-(4-(2-chlorophenyl)-9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo[3,4-c]carbazol-6(1H)-yl)-N-(2-(dimethylamino)ethyl)propanamide
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C27H25ClN4O4
 1
1
IC50 < 250 nM
   TI
   LI
   LO
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CP0009242
3-(4-(2-chlorophenyl)-9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo[3,4-c]carbazol-6(1H)-yl)propanenitrile
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C23H14ClN3O3
 1
1
IC50 < 250 nM
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Biochemical Assays
Compound ID Compound Name Compound Formula
CP0006340
Dinaciclib
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C21H28N6O2
 4
1 IC50 = 1 nM
2 IC50 = 3 nM
3 IC50 = 12 nM
4 IC50 = 72 nM
CP0001372
(2R,3R)-3-[2-[4-(cyclopropylsulfonimidoyl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]oxybutan-2-ol
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C18H21F3N4O3S
 1
1 IC50 = 7 nM
CP0005066
NR9
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C18H13N3OS2
 2
1 IC50 = 19 nM
2 Ki = 35 nM
CP0177375
ROCHE screening, 70
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C22H17N3OS
 1
1 Ki = 20 nM
CP0702723
(Z)-2-amino-5-(quinolin-6-ylmethylene)thiazol-4(5H)-one
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C13H9N3OS
 1
1 Ki = 150 nM
Clinical Information about the Protein
Target 1 ( Cyclin-dependent kinase 1 (CDK1) )
Target Type Clinical trial Target
Disease 10 Target-related Diseases  10
1 Breast cancer [ICD-11: 2C60-2C65]
2 Mantle cell lymphoma [ICD-11: 2A85.5]
3 Non-small-cell lung cancer [ICD-11: 2C25.Y]
4 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
5 Graft rejection [ICD-11: NE84]
6 Acute lymphoblastic leukaemia [ICD-11: 2A85]
7 Small-cell lung cancer [ICD-11: 2C25.Y]
8 Advanced solid tumour [ICD-11: 2A00-2F9Z]
9 Obesity [ICD-11: 5B81]
10 Pain [ICD-11: MG30-MG3Z]
Clinical Trial Drug(s) 6 Clinical Trial Drugs  6
1 P-276 Phase 2
Breast cancer
2 P276-00 Phase 2
Mantle cell lymphoma
3 R-roscovitine Phase 2
Non-small-cell lung cancer
4 Ro 31-7453 Phase 2
Solid tumour/cancer
5 AG-024322 Phase 1
Solid tumour/cancer
6 PHA-793887 Phase 1
Solid tumour/cancer
Discontinued Drug(s) 4 Discontinued Drugs  4
1 SCH 727965 Discontinued in Phase 3
Acute lymphoblastic leukaemia
2 BAY 10-00394 Discontinued in Phase 2
Small-cell lung cancer
3 R547 Discontinued in Phase 1
Advanced solid tumour
4 CGP-60474 Terminated
Solid tumour/cancer
Investigative Drug(s) 1 Investigative Drug  1
1 Microxine Investigative
Pain
Patented Agent(s) 1 Patented Agent  1
1 CHIR-99021 Patented
Graft rejection
Preclinical Drug(s) 1 Preclinical Drug  1
1 L-751250 Preclinical
Obesity
Similar Protein(s) and Bioactivity Statistics
50% Identity
Protein ID Protein Name Protein Organism
PT06662 Cyclin-dependent kinase 1 Mus musculus, Mouse