CDK1

Summary

CDK1 (cyclin dependent kinase 1, HGNC:1722) is a protein-coding gene on chromosome 10q21.2, encoding Cyclin-dependent kinase 1 (P06493). 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. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF), which is essential for G2/M phase transitions of eukaryotic cell cycle. Mitotic cyclins stably associate with this protein and function as regulatory subunits. The kinase activity of this protein is controlled by cyclin accumulation and destruction through the cell cycle. The phosphorylation and dephosphorylation of this protein also play important regulatory roles in cell cycle control. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 983 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 26 total
• Druggable target: yes — 60 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_001786

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1722
Approved symbol	CDK1
Name	cyclin dependent kinase 1
Location	10q21.2
Locus type	gene with protein product
Status	Approved
Aliases	CDC28A
Ensembl gene	ENSG00000170312
Ensembl biotype	protein_coding
OMIM	116940
Entrez	983

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000316629, ENST00000373809, ENST00000395284, ENST00000448257, ENST00000475504, ENST00000487784, ENST00000519078, ENST00000519760, ENST00000856536, ENST00000856537, ENST00000925683, ENST00000925684, ENST00000925685, ENST00000925686, ENST00000925687, ENST00000925688, ENST00000945041

RefSeq mRNA: 4 — MANE Select: NM_001786 NM_001170406, NM_001320918, NM_001786, NM_033379

CCDS: CCDS44408, CCDS7260

Canonical transcript exons

ENST00000395284 — 8 exons

Exon	Start	End
ENSE00001173251	60791890	60792053
ENSE00001173258	60792148	60792289
ENSE00001173279	60785664	60785787
ENSE00001461632	60793877	60794852
ENSE00001521217	60788060	60788230
ENSE00003478364	60784705	60784861
ENSE00003527529	60780141	60780202
ENSE00003892956	60778478	60778570

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 99.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.0557 / max 1398.8943, expressed in 1574 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105039	47.4417	1554
105040	8.4188	1200
105043	0.1953	94

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.21	gold quality
ganglionic eminence	UBERON:0004023	97.66	gold quality
embryo	UBERON:0000922	97.13	gold quality
trabecular bone tissue	UBERON:0002483	94.86	gold quality
secondary oocyte	CL:0000655	92.64	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.55	gold quality
rectum	UBERON:0001052	91.43	gold quality
bone marrow	UBERON:0002371	91.10	gold quality
adrenal tissue	UBERON:0018303	90.63	gold quality
endometrium epithelium	UBERON:0004811	90.30	gold quality
tibia	UBERON:0000979	88.83	gold quality
vermiform appendix	UBERON:0001154	88.45	gold quality
cartilage tissue	UBERON:0002418	88.32	gold quality
mucosa of transverse colon	UBERON:0004991	88.17	gold quality
stromal cell of endometrium	CL:0002255	88.07	gold quality
esophagus mucosa	UBERON:0002469	87.14	gold quality
gingival epithelium	UBERON:0001949	86.80	gold quality
lower esophagus mucosa	UBERON:0035834	86.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.58	gold quality
esophagus squamous epithelium	UBERON:0006920	86.55	gold quality
bone marrow cell	CL:0002092	85.78	gold quality
oral cavity	UBERON:0000167	85.48	gold quality
caecum	UBERON:0001153	85.40	gold quality
endometrium	UBERON:0001295	85.39	gold quality
oocyte	CL:0000023	85.38	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.04	gold quality
duodenum	UBERON:0002114	85.03	gold quality
lymph node	UBERON:0000029	84.41	gold quality
squamous epithelium	UBERON:0006914	84.39	gold quality
colonic mucosa	UBERON:0000317	84.09	gold quality

Single-cell (SCXA)

Detected in 26 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-MTAB-8894	yes	1416.82
E-MTAB-11121	yes	702.37
E-MTAB-6308	yes	689.90
E-HCAD-24	yes	581.15
E-CURD-79	yes	562.18
E-ENAD-17	yes	523.92
E-MTAB-6108	yes	401.11
E-MTAB-6505	yes	361.69
E-MTAB-7052	yes	332.34
E-HCAD-15	yes	284.86
E-CURD-114	yes	240.57
E-MTAB-7037	yes	238.84
E-MTAB-8142	yes	238.31
E-GEOD-84465	yes	228.73
E-HCAD-10	yes	44.35

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ELAVL1	Activation

Upstream regulators (CollecTRI, top): ARID3A, DNMT1, E2F1, E2F2, E2F3, E2F4, ERF, ETS2, ETV3, FOXM1, FOXO1, GLI2, GLI3, HCFC1, HOXA10, IRF1, KAT5, KCNIP3, KDM2B, KLF5, KMT2E, MYB, MYBL2, MYC, NANOG, NCOA3, NFYA, PAX1, PTTG1, RB1, SLC22A2, SMAD7, SP1, TFDP1, TP53, TP63, TP73, ZNF331

miRNA regulators (miRDB)

53 targeting CDK1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Cyclin b1 promoter activity and functional cdk1 complex formation in G1 phase of human breast cancer cells (PMID:11779217)
• Abolishment of the Tyr-15 inhibitory phosphorylation site on cdc2 reduces the radiation-induced G(2) delay, revealing a potential checkpoint in early mitosis. (PMID:11782384)
• effects of ergosterol and cholesteron on Cdk1 activation (PMID:11895447)
• role in regulating peroxiredoxin I activity by phosphorylation (PMID:11986303)
• activation in cells depleted of Plk1 by siRNA (PMID:12077309)
• Syncytia from cells expressing the HIV-1 Env gene fused with cells expressing CD4/CXCR4 undergo apoptosis after nuclear translocation of mTOR, mTOR-mediated p53 phosphorylation, p53-dependent Bax upregulation & mitochondrial death pathway activation. (PMID:12145207)
• mediates phosphorylation and mobilizes microtubule-organizing centers from the apical intermediate filament scaffold in CACO-2 epithelial cells (PMID:12151413)
• cdc2 might be involved in the abnormal hyperphosphorylation of tau and aggregation of tau into paired helical filaments at an early stage and increased cdc2 activity is not consequent to the deposition of beta-amyloid in Alzheimer disease brain. (PMID:12200623)
• in a complex with cyclin B, regulates function of WARTS on the mitotic apparatus (PMID:12372621)
• SET protein regulates G(2)/M transition by modulating cyclin B-CDK1 activity. (PMID:12407107)
• Cdc2 provides a signal that triggers inactivation of S6K1 in mitosis. (PMID:12586835)
• deregulation of cdc2 kinase activity can trigger apoptotic machinery that leads to caspase-3 activation and apoptosis. (PMID:12604359)
• Cdc2 is important regulator for cell cycle as well as for apoptosis (PMID:12742823)
• alphavbeta3 expression in LNCaP (beta3-LNCaP) prostate cancer cells causes increased cdc2 mRNA levels as evaluated by gene expression analysis, and increased cdc2 protein and kinase activity levels (PMID:12771130)
• CDC2 phosphorylates emi1 on a consensus site, is recognized by bTrCP ubiquitin ligase and is destroyed, thus delaying activation of the anaphase promoting complex. (PMID:12791267)
• The immunohistochemical expression of p34(cdc2) is independently associated with lymph node metastasis in colorectal carcinoma (PMID:12884029)
• nonphosphorylated CDC2 has a role in stimulating DNA replication, histone H3 phosphorylation, and cell division even after DNA damage (PMID:12912980)
• CDK1 phosphorylates hamartin at three sites, one of which (Thr417) is in the hamartin-tuberin interaction domain; phosphorylation of hamartin regulates the function of the hamartin-tuberin complex during the G2/M phase of the cell cycle (PMID:14551205)
• data suggest the maintenance of Cdk1/cyclin B1 activity in HCMV-infected cells can be explained by 3 mechanisms: accumulation of cyclin B1, inactivation of negative regulatory pathways for Cdk1, accumulation of positive factors that promote Cdk1 activity (PMID:14645578)
• could play an important role in gastric carcinoma progression and would be a novel target for the treatment of gastric carcinomas as well as a strong prognostic marker. (PMID:14654553)
• Increased expression of CDK1 may have important causative role in decreasing levels of p25 in patients with aggressive colorectal carcinoma (PMID:15073847)
• At the onset of mitosis, Cdk1 phosphorylates the peripheral Golgi protein Nir2 at multiple sites. (PMID:15125835)
• the induction of Cdc2 phosphorylation due to the increase of Wee1 and Myt1 as well as the reduction of Cdc2 and cyclin B1 are involved in 1,25[OH]2VD3-induced G2/M arrest of keratinocytes. (PMID:15175024)
• exposure to nonrepairable DNA damage leads to nuclear accumulation of inactive cyclin B1-Cdk1 complexes (PMID:15181148)
• role in regulating Fas ligand transcription (PMID:15215233)
• results suggest that centrosome-associated Chk1 shields centrosomal Cdk1 from unscheduled activation by cytoplasmic Cdc25B, thereby contributing to proper timing of the initial steps of cell division, including mitotic spindle formation (PMID:15311285)
• expression of pdcd4 as an indirect suppressor of CDK1/cdc2 is lost in progressed carcinomas of lung, breast, colon, and prostate. (PMID:15317660)
• models of cyclin-dependent kinase 1 complexed with flavopiridol and roscovitine (PMID:15474478)
• protein 4.1R mitotic regulation involves phosphorylation by cdc2 kinase (PMID:15525677)
• Inhibition of Cdc2 activity and the subsequent downregulation of survivin and XIAP by subtoxic doses of rottlerin contribute to amplification of caspase cascades. (PMID:15531913)
• Abi enhances Abl-mediated downregulation and phosphorylation of Cdc2 kinase (PMID:15591787)
• The level of mitotic Bloom syndrome protein phosphorylation reflects the level of cdc2 activity. (PMID:15604258)
• Cellular differentiation in squamous cell carcinoma of the esophagus may be mediated by an intracellular localization of p34(cdc2). (PMID:15662526)
• Cdk1-cyclin B is the major kinase phosphorylating GRASP65 in mitosis (PMID:15678101)
• results show that human papillomavirus type 16 E1 E4 does not inhibit the kinase activity of the Cdk1/cyclin B1 complex; instead, 16E1 E4 uses a novel mechanism in which it sequesters Cdk1/cyclin B1 onto the cytokeratin network (PMID:15767402)
• results strongly indicate that in response to genotoxic stress, Cdk5 activator-binding protein C53(C53) serves as an important regulatory component of DNA damage checkpoint through modulating cyclin dependent kinase 1-cyclin B1 function (PMID:15790566)
• Cdc2 inhibits growth factor receptor-mediated ERK activation during mitosis by primarily targeting signaling proteins that are upstream of MEK1 (PMID:15888452)
• Our results demonstrate that differential regulation of Cdc2 and Cdk2 activity by different doses of doxorubicin may contribute to the induction of two modes of cell death in hepatoma cells, either apoptosis or cell death through mitotic catastrophe. (PMID:16036217)
• Cdk1 inactivation is sufficient to activate a signaling pathway leading to cytokinesis, which emanates from mitotic spindles and is regulated by ECT2, MgcRacGAP, and RhoA (PMID:16118207)
• in nasopharyngeal carcinoma cells, SarCNU-induced apoptosis is p53-dependent while SarCNU-induced G2/M arrest is mediated by the cyclin B1-cdc-2 complex (PMID:16142332)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdk1	ENSDARG00000087554
mus_musculus	Cdk1	ENSMUSG00000019942
rattus_norvegicus	Cdk1	ENSRNOG00000000632
drosophila_melanogaster	Cdk1	FBGN0004106
caenorhabditis_elegans		WBGENE00000405

Paralogs (26): CDKL3 (ENSG00000006837), CDKL5 (ENSG00000008086), CDK11A (ENSG00000008128), CDK14 (ENSG00000058091), CDK17 (ENSG00000059758), CDK13 (ENSG00000065883), CDKL1 (ENSG00000100490), CDK16 (ENSG00000102225), CDK6 (ENSG00000105810), PRP4K (ENSG00000112739), CDK18 (ENSG00000117266), CDK2 (ENSG00000123374), CDK8 (ENSG00000132964), CDK7 (ENSG00000134058), CDK4 (ENSG00000135446), CDK9 (ENSG00000136807), CDK15 (ENSG00000138395), CDKL2 (ENSG00000138769), CDK19 (ENSG00000155111), CDK20 (ENSG00000156345), CDK5 (ENSG00000164885), CDK12 (ENSG00000167258), CDK10 (ENSG00000185324), CDKL4 (ENSG00000205111), CDK11B (ENSG00000248333), CDK3 (ENSG00000250506)

Protein

Protein identifiers

Cyclin-dependent kinase 1 — P06493 (reviewed: P06493)

Alternative names: Cell division control protein 2 homolog, Cell division protein kinase 1, p34 protein kinase

All UniProt accessions (3): P06493, A0A024QZP7, E5RIU6

UniProt curated annotations — full annotation on UniProt →

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. Phosphorylates PARVA/actopaxin, APC, AMPH, APC, ASB7, 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, UHRF1, KAT5, LMNA, LMNB, LBR, MKI67, 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, RBBP8/CtIP, 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. CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs. Essential for early stages of embryonic development. 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. 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. Phosphorylates KRT5 during prometaphase and metaphase. 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. Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression. Catalyzes lamin (LMNA, LMNB1 and LMNB2) phosphorylation at the onset of mitosis, promoting nuclear envelope breakdown. 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. The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis. 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. In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis. The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis. In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration. CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis. 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. Phosphorylates EML3 at ‘Thr-881’ which is essential for its interaction with HAUS augmin-like complex and TUBG1. Phosphorylates CGAS during mitosis, leading to its inhibition, thereby preventing CGAS activation by self DNA during mitosis. Phosphorylates SKA3 on multiple sites during mitosis which promotes SKA3 binding to the NDC80 complex and anchoring of the SKA complex to kinetochores, to enable stable attachment of mitotic spindle microtubules to kinetochores. (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry.

Subunit / interactions. Forms a stable but non-covalent complex with a regulatory subunit and with a cyclin. The cyclin subunit imparts substrate specificity to the complex. Interacts with cyclins-B (CCNB1, CCNB2 and CCNB3) to form a serine/threonine kinase holoenzyme complex also known as maturation promoting factor (MPF). Promotes G2-M transition when in complex with a cyclin-B. Can also form CDK1-cylin-D and CDK1-cyclin-E complexes that phosphorylate RB1 in vitro. Associates with cyclins-A and B1 during S-phase in regenerating hepatocytes. Interacts with DLGAP5. Binds to the CDK inhibitors CDKN1A/p21 and CDKN1B/p27. Interacts with catalytically active CCNB1 and RALBP1 during mitosis to form an endocytotic complex during interphase. Interacts with FANCC. Interacts with CEP63; this interaction recruits CDK1 to centrosomes. Interacts with CENPA. Interacts with NR1D1. Interacts with proteasome subunit PSMA8; to participate in meiosis progression during spermatogenesis. Unable to complex with cyclin-B1 and also fails to bind to CDKN1A/p21. (Microbial infection) Interacts with severe fever with thrombocytopenia syndrome virus (SFTSV) NSs; this interaction is inclusion body dependent, it inhibits the formation and nuclear import of the cyclin B1-CDK1 complex and leads to cell cycle arrest.

Subcellular location. Nucleus. Cytoplasm. Mitochondrion. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle.

Tissue specificity. Found in breast cancer tissues.

Post-translational modifications. Phosphorylation at Thr-161 by CAK/CDK7 activates kinase activity. Phosphorylation at Thr-14 and Tyr-15 by PKMYT1 prevents nuclear translocation. Phosphorylation at Tyr-15 by WEE1 and WEE2 inhibits the protein kinase activity and acts as a negative regulator of entry into mitosis (G2 to M transition). Phosphorylation by PKMYT1 and WEE1 takes place during mitosis to keep CDK1-cyclin-B complexes inactive until the end of G2. By the end of G2, PKMYT1 and WEE1 are inactivated, but CDC25A and CDC25B are activated. Dephosphorylation by active CDC25A and CDC25B at Thr-14 and Tyr-15, leads to CDK1 activation at the G2-M transition. Phosphorylation at Tyr-15 by WEE2 during oogenesis is required to maintain meiotic arrest in oocytes during the germinal vesicle (GV) stage, a long period of quiescence at dictyate prophase I, leading to prevent meiotic reentry. Phosphorylation by WEE2 is also required for metaphase II exit during egg activation to ensure exit from meiosis in oocytes and promote pronuclear formation. Phosphorylated at Tyr-4 by PKR/EIF2AK2 upon genotoxic stress. This phosphorylation triggers CDK1 polyubiquitination and subsequent proteolysis, thus leading to G2 arrest. In response to UV irradiation, phosphorylation at Tyr-15 by PRKCD activates the G2/M DNA damage checkpoint. Polyubiquitinated upon genotoxic stress.

Activity regulation. Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-161 activates it. Activated through a multistep process; binding to cyclin-B is required for relocation of cyclin-kinase complexes to the nucleus, activated by CAK/CDK7-mediated phosphorylation on Thr-161, and CDC25-mediated dephosphorylation of inhibitory phosphorylation on Thr-14 and Tyr-15. Activity is restricted during S-phase in an ATR-dependent manner to prevent premature entry into G2. Repressed by the CDK inhibitors CDKN1A/p21 and CDKN1B/p27 during the G1 phase and by CDKN1A/p21 at the G1-S checkpoint upon DNA damage. Transient activation by rapid and transient dephosphorylation at Tyr-15 triggered by TGFB1. Inhibited by flavopiridol and derivatives, pyrimidine derivatives, pyridine derivatives, purine derivatives, staurosporine, paullones, oxoindoles, indazole analogs, indolin-2-ones, pyrazolo[3,4-b]pyridines, imidazo[1,2-a]pyridine (AZ703), thiazolinone analogs(RO-3306), thiazol urea, macrocyclic quinoxalin-2-one, pyrrolo[2,3-a]carbazole, pyrazolo[1,5-a]-1,3,5-triazine, pyrazolo[1,5-a]pyrimidine (Dinaciclib, SCH 727965), 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine), olomoucine, AG-024322, AT-7519, P276-00, R547/Ro-4584820 and SNS-032/BMS-387032.

Induction. Follows a cyclic expression; during interphase, accumulates gradually following G1, S to reach a critical threshold at the end of G2, which promotes self-activation and triggers onset of mitosis. Induced transiently by TGFB1 at an early phase of TGFB1-mediated apoptosis, but later repressed. Triggered by CKS1B during mitotic entry in breast cancer cells. Down-regulated under genotoxic stresses triggered by PKR/EIF2AK2-mediated phosphorylation.

Miscellaneous. As a key regulator of the cell cycle, CDK1 is a potent therapeutic target for inhibitors in cancer treatment.

Similarity. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P06493-1	1	yes
P06493-2	2, CDC2deltaT

RefSeq proteins (3): NP_001307847, NP_001777, NP_203698 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR050108	CDK	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.22 — cyclin-dependent kinase (BRENDA: 49 organisms, 441 substrates, 555 inhibitors, 8 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ADAQHATPPKKKRKVEDPKDF	0.046–0.521	2
ATP	0.0052–0.017	2
FIN1	0.003	1
PKTPKKAKKL	0.0029	1

Catalyzed reactions (Rhea), 3 shown:

• [DNA-directed RNA polymerase] + ATP = phospho-[DNA-directed RNA polymerase] + ADP + H(+) (RHEA:10216)
• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (59 total): helix 17, modified residue 15, strand 10, turn 5, cross-link 4, mutagenesis site 2, binding site 2, chain 1, domain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
6GU2	X-RAY DIFFRACTION	2
5LQF	X-RAY DIFFRACTION	2.06
6TWN	X-RAY DIFFRACTION	2.28
4Y72	X-RAY DIFFRACTION	2.3
5HQ0	X-RAY DIFFRACTION	2.3
6GU6	X-RAY DIFFRACTION	2.33
4YC6	X-RAY DIFFRACTION	2.6
6GU3	X-RAY DIFFRACTION	2.65
4YC3	X-RAY DIFFRACTION	2.7
6GU4	X-RAY DIFFRACTION	2.73
6GU7	X-RAY DIFFRACTION	2.75
9SKQ	ELECTRON MICROSCOPY	3.4
7NJ0	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06493-F1	89.52	0.70

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 128 (proton acceptor)

Ligand- & substrate-binding residues (2): 10–18; 33

Post-translational modifications (19): 15, 19, 39, 77, 141, 161, 178, 222, 245, 248, 6, 9, 20, 139, 1, 4, 6, 9, 14

Mutagenesis-validated functional residues (2):

Position	Phenotype
4	constitutive polyubiquitination.
14–15	abnormal cell cycle exhibiting only m-phase without completing either karyokinesis or cytokinesis.

Function

Pathways and Gene Ontology

Reactome pathways

80 pathways

ID	Pathway
R-HSA-110056	MAPK3 (ERK1) activation
R-HSA-113507	E2F-enabled inhibition of pre-replication complex formation
R-HSA-1362300	Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1
R-HSA-162658	Golgi Cisternae Pericentriolar Stack Reorganization
R-HSA-174048	APC/C:Cdc20 mediated degradation of Cyclin B
R-HSA-174184	Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-HSA-176408	Regulation of APC/C activators between G1/S and early anaphase
R-HSA-176412	Phosphorylation of the APC/C
R-HSA-176417	Phosphorylation of Emi1
R-HSA-2299718	Condensation of Prophase Chromosomes
R-HSA-2465910	MASTL Facilitates Mitotic Progression
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-2514853	Condensation of Prometaphase Chromosomes
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-2980767	Activation of NIMA Kinases NEK9, NEK6, NEK7
R-HSA-2995383	Initiation of Nuclear Envelope (NE) Reformation
R-HSA-3301854	Nuclear Pore Complex (NPC) Disassembly
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-4419969	Depolymerization of the Nuclear Lamina
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-5687128	MAPK6/MAPK4 signaling
R-HSA-5689896	Ovarian tumor domain proteases
R-HSA-6804114	TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest
R-HSA-6804757	Regulation of TP53 Degradation
R-HSA-68875	Mitotic Prophase
R-HSA-69205	G1/S-Specific Transcription
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition

MSigDB gene sets: 916 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_CIRCADIAN_RHYTHM, E2F_Q4, GOBP_SINGLE_FERTILIZATION, GOBP_CHROMOSOME_ORGANIZATION, SA_G2_AND_M_PHASES, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, MODULE_52, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EPITHELIUM_DEVELOPMENT, HORIUCHI_WTAP_TARGETS_DN

GO Biological Process (65): G1/S transition of mitotic cell cycle (GO:0000082), G2/M transition of mitotic cell cycle (GO:0000086), microtubule cytoskeleton organization (GO:0000226), DNA replication (GO:0006260), DNA repair (GO:0006281), apoptotic process (GO:0006915), DNA damage response (GO:0006974), mitotic nuclear membrane disassembly (GO:0007077), mitotic G2 DNA damage checkpoint signaling (GO:0007095), centrosome cycle (GO:0007098), pronuclear fusion (GO:0007344), response to toxic substance (GO:0009636), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), regulation of Schwann cell differentiation (GO:0014038), response to amine (GO:0014075), response to activity (GO:0014823), cell migration (GO:0016477), protein deubiquitination (GO:0016579), peptidyl-threonine phosphorylation (GO:0018107), chromosome condensation (GO:0030261), epithelial cell differentiation (GO:0030855), negative regulation of protein ubiquitination (GO:0031397), protein localization to kinetochore (GO:0034501), positive regulation of protein import into nucleus (GO:0042307), regulation of circadian rhythm (GO:0042752), negative regulation of apoptotic process (GO:0043066), response to ethanol (GO:0045471), positive regulation of DNA replication (GO:0045740), regulation of embryonic development (GO:0045995), response to cadmium ion (GO:0046686), response to copper ion (GO:0046688), fibroblast proliferation (GO:0048144), rhythmic process (GO:0048511), response to axon injury (GO:0048678), cell division (GO:0051301), ventricular cardiac muscle cell development (GO:0055015), positive regulation of cardiac muscle cell proliferation (GO:0060045), positive regulation of mitotic sister chromatid segregation (GO:0062033)

GO Molecular Function (16): virus receptor activity (GO:0001618), chromatin binding (GO:0003682), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), cyclin-dependent protein serine/threonine kinase activity (GO:0004693), ATP binding (GO:0005524), RNA polymerase II CTD heptapeptide repeat kinase activity (GO:0008353), kinase activity (GO:0016301), cyclin binding (GO:0030332), Hsp70 protein binding (GO:0030544), histone kinase activity (GO:0035173), cyclin-dependent protein kinase activity (GO:0097472), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (20): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), endoplasmic reticulum membrane (GO:0005789), centrosome (GO:0005813), cytosol (GO:0005829), spindle microtubule (GO:0005876), membrane (GO:0016020), midbody (GO:0030496), extracellular exosome (GO:0070062), mitotic spindle (GO:0072686), cyclin A1-CDK1 complex (GO:0097121), cyclin A2-CDK1 complex (GO:0097122), cyclin B1-CDK1 complex (GO:0097125), spindle (GO:0005819), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Mitotic Prophase	3
Mitotic Prometaphase	2
Nuclear Envelope Breakdown	2
Centrosome maturation	2
RAF-independent MAPK1/3 activation	1
E2F mediated regulation of DNA replication	1
G0 and Early G1	1
APC/C:Cdc20 mediated degradation of mitotic proteins	1
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	1
APC/C-mediated degradation of cell cycle proteins	1
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	1
Regulation of APC/C activators between G1/S and early anaphase	1
G2/M Transition	1
Nuclear Envelope (NE) Reassembly	1
Loss of proteins required for interphase microtubule organization from the centrosome	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein kinase activity	4
mitotic cell cycle	3
cyclin-dependent protein kinase holoenzyme complex	3
mitotic cell cycle phase transition	2
DNA metabolic process	2
gene expression	2
regulation of gene expression	2
binding	2
protein serine/threonine kinase activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
spindle	2
intracellular membraneless organelle	2
cell cycle G1/S phase transition	1
cell cycle G2/M phase transition	1
cytoskeleton organization	1
microtubule-based process	1
DNA biosynthetic process	1
DNA damage response	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to stress	1
nuclear membrane disassembly	1
mitotic cell cycle process	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G2/M transition checkpoint	1
cell cycle process	1
microtubule organizing center organization	1
karyogamy	1
single fertilization	1
response to chemical	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G2/M phase transition	1

Protein interactions and networks

STRING

7676 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK1	CCNB1	P14635	999
CDK1	CCNL2	Q96S94	999
CDK1	CCNA1	P78396	998
CDK1	CCNA2	P20248	998
CDK1	CCNB2	O95067	996
CDK1	BUB1B	O60566	995
CDK1	CDKN1A	P38936	987
CDK1	CDC20	Q12834	985
CDK1	CCND1	P24385	984
CDK1	CKS1B	P33551	978
CDK1	CDK2	P24941	977
CDK1	CDC25C	P30307	976
CDK1	CKS2	P33552	968
CDK1	BUB1	O43683	964
CDK1	WEE1	P30291	958

IntAct

328 interactions, top by confidence:

A	B	Type	Score
CCNB1	CDK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.980
CCNB1	CDK1	psi-mi:“MI:0407”(direct interaction)	0.980
CDK1	CCNB1	psi-mi:“MI:0407”(direct interaction)	0.980
CDK1	CCNB1	psi-mi:“MI:0915”(physical association)	0.980
CCNB1	CDK1	psi-mi:“MI:0915”(physical association)	0.980
CCNB1	CDK1	psi-mi:“MI:0570”(protein cleavage)	0.980
CDK1	CKS1B	psi-mi:“MI:0915”(physical association)	0.920
CDKN1A	CDK1	psi-mi:“MI:0914”(association)	0.900
CDKN1A	CDK1	psi-mi:“MI:0915”(physical association)	0.900
CDK1	CDKN1A	psi-mi:“MI:0915”(physical association)	0.900
CDK1	CDKN1B	psi-mi:“MI:0914”(association)	0.890
CDK1	CDKN1B	psi-mi:“MI:0915”(physical association)	0.890
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
CDK2	CCNB2	psi-mi:“MI:0914”(association)	0.860
CDK1	CCNB2	psi-mi:“MI:0914”(association)	0.840
GMNN	MCIDAS	psi-mi:“MI:0914”(association)	0.770
PPP2R1B	STRN	psi-mi:“MI:0914”(association)	0.730
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
PKMYT1	CCNB2	psi-mi:“MI:0914”(association)	0.730
EGFR	CDK1	psi-mi:“MI:0915”(physical association)	0.670
CDK1	FOXO1	psi-mi:“MI:0217”(phosphorylation reaction)	0.650
FOXO1	CDK1	psi-mi:“MI:0915”(physical association)	0.650

BioGRID (1091): HSP90AA1 (Affinity Capture-Western), CDC37 (Affinity Capture-Western), HSPA4 (Affinity Capture-Western), ABL1 (Biochemical Activity), SIRT1 (Biochemical Activity), CDK1 (Affinity Capture-Western), HIST1H1A (Biochemical Activity), CDK1 (Affinity Capture-MS), CDK1 (Affinity Capture-Western), BTRC (Affinity Capture-Western), CDK1 (Biochemical Activity), CDK1 (Affinity Capture-MS), CDK1 (Affinity Capture-Western), CKS1B (Two-hybrid), CDK1 (Affinity Capture-Western)

ESM2 similar proteins: A8WIP6, A8XA58, G5EFV5, O96821, P00546, P04551, P06242, P06493, P11440, P13863, P17157, P23573, P24033, P34556, P35567, P38973, P39951, P43063, P48734, P49615, P51166, P51958, P54119, P54664, Q00535, Q00646, Q02399, Q03114, Q06309, Q26671, Q27032, Q2V419, Q38775, Q4Y4B1, Q4Z6R1, Q5RCH1, Q64261, Q6FKD4, Q6ZAG3, Q7RM49

Diamond homologs: A1CL96, A1D624, A2QU77, A2X6X1, A2XUW1, A3LUB9, A4QXX4, A8XA58, O13958, O55076, O61847, O96821, P00546, P06493, P0C661, P0CS76, P0CS77, P11440, P21127, P23111, P23437, P23572, P24033, P24100, P24788, P24923, P24941, P29618, P29619, P34112, P34117, P34556, P35567, P39073, P39951, P43063, P43450, P46892, P48734, P48963

SIGNOR signaling

200 interactions.

A	Effect	B	Mechanism
CDK1	“down-regulates activity”	MCM4	phosphorylation
CDK1	“down-regulates activity”	PIK3C2A	phosphorylation
CDK1	“up-regulates activity”	KIF22	phosphorylation
CDK1	“up-regulates activity”	RAD9A	phosphorylation
CDK1	“down-regulates activity”	NSFL1C	phosphorylation
CDK1	“up-regulates activity”	LIG1	phosphorylation
CDK1	“down-regulates activity”	FEN1	phosphorylation
CDK1	“down-regulates activity”	EIF4EBP1	phosphorylation
CDK1	down-regulates	CUX1	phosphorylation
CDK1	up-regulates	RPS6KB1	phosphorylation
CDK1	down-regulates	ESPL1	phosphorylation
CDK1	up-regulates	BIRC5	phosphorylation
CDK1	up-regulates	ORC1	phosphorylation
CDK1	up-regulates	UBE2A	phosphorylation
CDK1	unknown	TSC1	phosphorylation
CDK1	down-regulates	TSC1	phosphorylation
CDK1	up-regulates	ANAPC1	phosphorylation
CDK1	up-regulates	CDC16	phosphorylation
CDK1	up-regulates	CDC23	phosphorylation
CDK1	up-regulates	CDC27	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 184 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
TP53 Regulates Transcription of Cell Cycle Genes	8	35.1×	2e-09
G1 Phase	11	34.9×	6e-13
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	6	30.7×	8e-07
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	5	28.8×	1e-05
p53-Dependent G1 DNA Damage Response	5	28.8×	1e-05
p53-Dependent G1/S DNA damage checkpoint	5	28.8×	1e-05
G1/S DNA Damage Checkpoints	5	27.1×	1e-05
G1/S Transition	14	26.3×	2e-14

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cyclin-dependent protein serine/threonine kinase activity	5	23.3×	3e-04
peptidyl-tyrosine phosphorylation	8	21.5×	8e-07
G2/M transition of mitotic cell cycle	10	19.9×	3e-08
G1/S transition of mitotic cell cycle	15	19.2×	2e-12
extrinsic apoptotic signaling pathway via death domain receptors	6	15.3×	3e-04
positive regulation of fibroblast proliferation	7	13.2×	2e-04
positive regulation of G1/S transition of mitotic cell cycle	5	12.8×	3e-03
regulation of mitotic cell cycle	8	12.3×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

26 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1143 predictions. Top by Δscore:

Variant	Effect	Δscore
10:60778566:GCCGG:G	donor_gain	1.0000
10:60780136:TTTAG:T	acceptor_loss	1.0000
10:60780137:TTAG:T	acceptor_loss	1.0000
10:60780138:TAG:T	acceptor_loss	1.0000
10:60780139:A:AT	acceptor_loss	1.0000
10:60780140:G:A	acceptor_loss	1.0000
10:60780200:AAGG:A	donor_loss	1.0000
10:60780201:AGG:A	donor_loss	1.0000
10:60780203:G:A	donor_loss	1.0000
10:60780204:T:A	donor_loss	1.0000
10:60780751:T:TA	acceptor_gain	1.0000
10:60785662:A:AG	acceptor_gain	1.0000
10:60785663:G:GA	acceptor_gain	1.0000
10:60785785:AAGGT:A	donor_loss	1.0000
10:60785786:AGGTA:A	donor_loss	1.0000
10:60785787:GG:G	donor_loss	1.0000
10:60785788:GTAAA:G	donor_loss	1.0000
10:60785789:T:G	donor_loss	1.0000
10:60791887:TAGG:T	acceptor_loss	1.0000
10:60791888:A:T	acceptor_loss	1.0000
10:60791889:G:T	acceptor_loss	1.0000
10:60791889:GGTA:G	acceptor_gain	1.0000
10:60792050:TCAG:T	donor_loss	1.0000
10:60792051:CAGGT:C	donor_loss	1.0000
10:60792054:G:A	donor_loss	1.0000
10:60792143:TTTA:T	acceptor_loss	1.0000
10:60792144:TTA:T	acceptor_loss	1.0000
10:60792145:TAGA:T	acceptor_loss	1.0000
10:60792146:A:AG	acceptor_gain	1.0000
10:60792146:AGAG:A	acceptor_loss	1.0000

AlphaMissense

1954 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:60780196:G:A	G11R	1.000
10:60780196:G:C	G11R	1.000
10:60780197:G:A	G11E	1.000
10:60780202:G:A	G13S	1.000
10:60780202:G:C	G13R	1.000
10:60780202:G:T	G13C	1.000
10:60784705:G:A	G13D	1.000
10:60784713:G:A	G16R	1.000
10:60784713:G:C	G16R	1.000
10:60784714:G:A	G16E	1.000
10:60784714:G:T	G16V	1.000
10:60784719:G:A	V18M	1.000
10:60784720:T:A	V18E	1.000
10:60784759:C:A	A31D	1.000
10:60784764:A:C	K33Q	1.000
10:60784764:A:G	K33E	1.000
10:60784765:A:T	K33I	1.000
10:60784766:A:C	K33N	1.000
10:60784766:A:T	K33N	1.000
10:60784794:G:A	G43R	1.000
10:60784794:G:C	G43R	1.000
10:60784816:G:C	R50P	1.000
10:60784818:G:A	E51K	1.000
10:60784819:A:T	E51V	1.000
10:60784820:A:C	E51D	1.000
10:60784820:A:T	E51D	1.000
10:60784858:T:A	V64D	1.000
10:60785702:T:C	L78P	1.000
10:60785729:T:C	L87P	1.000
10:60788084:G:A	G115R	1.000

dbSNP variants (sampled 300 via entrez): RS1000038943 (10:60785474 G>A,C), RS1000084128 (10:60791596 A>G), RS1000115184 (10:60791811 C>G), RS1000633072 (10:60787055 G>A), RS1000728643 (10:60779442 C>G,T), RS1000909506 (10:60782397 A>T), RS1000911693 (10:60789117 G>A,T), RS1001003693 (10:60786705 A>C,G), RS1001009835 (10:60776664 A>G), RS1001127115 (10:60793583 A>C), RS1001509319 (10:60777430 G>A), RS1001565275 (10:60777748 G>C), RS1001608041 (10:60788185 C>T), RS1001766854 (10:60781738 C>T), RS1002098265 (10:60794977 C>T)

Disease associations

OMIM: gene MIM:116940 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002062_3	Reading and spelling	3.000000e-06
GCST002142_15	Cocaine dependence	5.000000e-06
GCST002142_9	Cocaine dependence	3.000000e-06
GCST009438_7	Voxel-wise structural brain imaging measurements in Alzheimer’s disease	7.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005301	reading and spelling ability
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (14): CHEMBL1907602 (PROTEIN COMPLEX), CHEMBL2094127 (PROTEIN COMPLEX GROUP), CHEMBL3038467 (PROTEIN COMPLEX), CHEMBL3038468 (PROTEIN COMPLEX), CHEMBL308 (SINGLE PROTEIN), CHEMBL3559691 (PROTEIN FAMILY), CHEMBL3885551 (PROTEIN COMPLEX), CHEMBL4296065 (PROTEIN COMPLEX), CHEMBL4296066 (PROTEIN COMPLEX), CHEMBL4523683 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

60 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 168,285 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL1173055	RUCAPARIB	4	7,009
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL1096380	PLINABULIN	3	686
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL407874	6-O-BENZYLGUANINE	3	6,988
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL50	QUERCETIN	3	74,559
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL1276127	INDIRUBIN	2	181
CHEMBL14762	SELICICLIB	2	3,787
CHEMBL1944698	ZOTIRACICLIB	2	2,915
CHEMBL2347597	ASNUCICLIB	2	100
CHEMBL3115681	NARAZACICLIB	2	287
CHEMBL3655762	CYC-065	2	388
CHEMBL3905910	VORUCICLIB	2	856
CHEMBL4442620	RONICICLIB	2
CHEMBL445813	AT-7519	2
CHEMBL4462530	ZEMIRCICLIB	2
CHEMBL5095094	CULMERCICLIB	2
CHEMBL564829	MILCICLIB	2
CHEMBL8260	BAICALEIN	2
CHEMBL151	LUTEOLIN	2
CHEMBL31574	FISETIN	2
CHEMBL3545283	RIVICICLIB	2
CHEMBL4277900	CROZBACICLIB	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10711	Toxicity	3	radiotherapy	Pneumonitis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10711	CDK1	3	3.00	1	radiotherapy

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — CDK1 subfamily

Most potent curated ligand interactions (46 total), top 25:

Ligand	Action	Affinity	Parameter
alsterpaullone 2-cyanoethyl	Inhibition	9.64	pIC50
tanuxiciclib	Inhibition	9.22	pIC50
Cdk1/2 inhibitor III	Inhibition	9.22	pIC50
R547	Inhibition	8.7	pKi
RGB-286638	Inhibition	8.7	pIC50
dinaciclib	Inhibition	8.52	pIC50
asnuciclib	Inhibition	8.4	pKi
BMS-265246	Inhibition	8.22	pIC50
JNJ-7706621	Inhibition	8.19	pIC50
roniciclib	Inhibition	8.15	pIC50
zotiraciclib	Inhibition	8.05	pIC50
AZD5438	Inhibition	7.8	pIC50
QR-6401	Inhibition	7.66	pIC50
voruciclib	Inhibition	7.6	pIC50
compound 89S [PMID: 19115845]	Inhibition	7.52	pIC50
aminopurvalanol A	Inhibition	7.48	pIC50
BS-194	Inhibition	7.48	pIC50
alsterpaullone	Inhibition	7.46	pIC50
(R)-CR8	Inhibition	7.39	pIC50
RO3306	Inhibition	7.33	pIC50
7-hydroxystaurosporine	Inhibition	7.3	pIC50
(S)-CR8	Inhibition	7.22	pIC50
compound 9b [PMID: 18986805]	Inhibition	7.22	pIC50
kinase inhibitor 2 [PMID: 30199702]	Inhibition	7.15	pIC50
riviciclib	Inhibition	7.1	pIC50

Binding affinities (BindingDB)

660 measured of 995 human assays (1010 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
BDBM50375663	IC50	0.23 nM
4-{[3-(4-aminophenyl)-1H-pyrazol-5-yl]amino}benzene-1-sulfonamide	IC50	0.34 nM
(12Z)-12-{[(4-{[2-(2-hydroxyethoxy)ethyl]sulfamoyl}phenyl)amino]methylidene}-3-thia-5,10-diazatricyclo[7.3.0.0^{2,6}]dodeca-1,4,6,8-tetraen-11-one	IC50	0.54 nM
5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-N-(pyrimidin-4-yl)-1,3-thiazol-2-amine	IC50	1 nM
N-methyl-4-({[(12Z)-11-oxo-3-thia-5,10-diazatricyclo[7.3.0.0^{2,6}]dodeca-1,4,6,8-tetraen-12-ylidene]methyl}amino)-N-(2,5,8,11-tetraoxatridecan-13-yl)benzene-1-sulfonamide	IC50	1 nM
4-{2-[(3Z)-4-(2-methylpropyl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzene-1-sulfonamide	IC50	1.2 nM
1-(2,6-difluorophenyl)-3-{3-[5-(morpholin-4-ylmethyl)-1H-1,3-benzodiazol-2-yl]-1H-pyrazol-4-yl}urea	IC50	1.5 nM
4-{2-[(3Z)-4-(2-methylprop-1-en-1-yl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzene-1-sulfonamide	IC50	1.5 nM
4-({[(3Z)-4-oxo-5,10-diazatricyclo[7.4.0.0^{2,6}]trideca-1,6,8,10,12-pentaen-3-ylidene]methyl}amino)benzene-1-sulfonamide	IC50	1.5 nM
4-[N -2-Oxo-2,3-dihydropyrrolo[3,2-f]quinolin-1-ylidene)-hydrazino]benzenesulfonamide	IC50	1.6 nM
3-{[4-(Aminosulfonyl)phenyl]hydrazono}-N-(2,6-dimethoxybenzyl)-2-oxo-5-indolinecarboxamide	IC50	1.7 nM
4-({[(3Z)-5-(3-methylbutanoyl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}amino)benzene-1-sulfonamide	IC50	1.9 nM
2-N-(1-methanesulfonylpiperidin-4-yl)-5-[(2,3,4-trifluoro-6-methoxyphenyl)carbonyl]pyrimidine-2,4-diamine	KI	2 nM
(2R,3R)-3-[[5-bromo-2-[3-methoxy-4-(methylsulfonimidoyl)anilino]pyrimidin-4-yl]amino]butan-2-ol	IC50	2 nM	US-8507510: Sulfoximine-substituted pyrimidines as CDK- and/or VEGF inhibitors, their production and use as pharmaceutical agents
(2S,3R)-3-[[5-bromo-2-[3-methoxy-4-(methylsulfonimidoyl)anilino]pyrimidin-4-yl]amino]butan-2-ol	IC50	2 nM	US-8507510: Sulfoximine-substituted pyrimidines as CDK- and/or VEGF inhibitors, their production and use as pharmaceutical agents
(3R)-3-[[5-bromo-2-[3-methoxy-4-(methylsulfonimidoyl)anilino]pyrimidin-4-yl]amino]-2-methylbutan-2-ol	IC50	2 nM	US-8507510: Sulfoximine-substituted pyrimidines as CDK- and/or VEGF inhibitors, their production and use as pharmaceutical agents
N-(2,6-Difluorophenyl)-N-[5-[[[5-tert-butyl-2-oxazolyl]-methyl]thio]-2-thiazolyl]urea	IC50	2 nM
5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-N-(pyridin-2-yl)-1,3-thiazol-2-amine	IC50	2 nM
N-{4-[(5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-1,3-thiazol-2-yl)amino]phenyl}-2-hydroxyethane-1-sulfonamido	IC50	2 nM
4-[1-(5-Oxazol-5-yl-2-oxo-1,2-dihydro-indol-3-ylidene)-ethylamino]benzenesulfonamide	IC50	2 nM
4-[[5-Amino-1-[(3-fluoro-2-thienyl)carbonyl]-1H-1,2,4-triazol-3-yl]amino]-benzenesulfonamide	IC50	2.1 nM
methyl (3Z)-2-oxo-3-{[(4-sulfamoylphenyl)amino]methylidene}-2,3-dihydro-1H-indole-5-carboxylate	IC50	2.1 nM
3-{[4-(Aminosulfonyl)phenyl]hydrazono}-2-oxo-N-(3-pyridinylmethyl)-2,3-dihydro-1H-indole-5-carboxamide	IC50	2.1 nM
4-[N -(1-Chloro-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-e]indazol-8-ylidene)-hydrazino]benzenesulfonamide	IC50	2.2 nM
4-{2-[(3Z)-5-(1,3-oxazol-5-yl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzene-1-sulfonamide	IC50	2.3 nM
4-({[(3Z)-5-(1,3-oxazol-5-yl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}amino)benzene-1-sulfonamide	IC50	2.5 nM
4-[N’-(4-Isopropyl-2-oxo-1,2-dihydro-indol-3-ylidene)-hydrazino]benzenesulfonamide	IC50	2.5 nM
1-(2-fluorophenyl)-3-{3-[5-(morpholin-4-ylmethyl)-1H-1,3-benzodiazol-2-yl]-1H-pyrazol-4-yl}urea	IC50	2.8 nM
4-({[(12Z)-11-oxo-3-thia-5,10-diazatricyclo[7.3.0.0^{2,6}]dodeca-1,4,6,8-tetraen-12-ylidene]methyl}amino)benzene-1-sulfonamide	IC50	2.8 nM
2,4-Diamino-5-ketopyrimidine 39	KI	3 nM
(2R,3R)-3-[2-[4-(2-hydroxyethylsulfonyl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]oxybutan-2-ol	IC50	3 nM	US-8802686: Sulfone-substituted anilinopyrimidine derivatives as CDK inhibitors, the production thereof, and use as a medicine
(2R,3R)-3-[[5-bromo-2-[4-(2-hydroxyethylsulfonimidoyl)anilino]pyrimidin-4-yl]amino]butan-2-ol	IC50	3 nM	US-8507510: Sulfoximine-substituted pyrimidines as CDK- and/or VEGF inhibitors, their production and use as pharmaceutical agents
4-N-(2,6-difluorobenzene)-3-N-(4-fluorophenyl)-1H-pyrazole-3,4-diamido	IC50	3 nM
3-(5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-1,3-thiazol-2-yl)-1-(2,6-dichlorophenyl)urea	IC50	3 nM
N-[5-[[[5-tert-Butyl-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-[[[bis(hydroxymethyl)methyl]amino]methyl]benzeneacetamide Hydrochloride Salt	IC50	3 nM
5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-N-(pyridin-3-yl)-1,3-thiazol-2-amine	IC50	3 nM
3-[({6-[(5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-1,3-thiazol-2-yl)amino]pyridin-3-yl}methyl)amino]-2,2-dimethylpropan-1-ol	IC50	3 nM
Isobutyl 3-{[4-(aminosulfonyl)anilino]methylene}-2-oxo-2,3-dihydro-1H-indole-5-carboxylate	IC50	3 nM
CDK Inhibitor, 13	KI	3 nM
4-[[5-Amino-1-(2,3,6-trifluorobenzoyl)-1H-1,2,4-triazol-3-yl]amino]-benzenesulfonamide	IC50	3.2 nM
4-({5-amino-1-[(3,5-dimethylthiophen-2-yl)carbonyl]-1H-1,2,4-triazol-3-yl}amino)benzene-1-sulfonamide	IC50	3.2 nM
3-amino-N-(2,6-difluorophenyl)-5-[(4-sulfamoylphenyl)amino]-1H-1,2,4-triazole-1-carbothioamide	IC50	3.2 nM
8-{[4-({[Amino(imino)methyl]amino}sulfonyl)anilino]-methylene}-7-oxo-7,8-dihydro-6H-[1,3]thiazolo[5,4-e]indole	IC50	3.3 nM
4-{2-[(3Z)-2-oxo-4-(propan-2-yloxy)-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzene-1-sulfonamide	IC50	3.4 nM
N-{3-[5-(morpholin-4-ylmethyl)-1H-1,3-benzodiazol-2-yl]-1H-pyrazol-4-yl}benzamide	IC50	3.5 nM
N-[2-(1H-imidazol-5-yl)ethyl]-4-({[(12Z)-11-oxo-3-thia-5,10-diazatricyclo[7.3.0.0^{2,6}]dodeca-1,4,6,8-tetraen-12-ylidene]methyl}amino)benzene-1-sulfonamide	IC50	3.6 nM
5-Amino-3-[[4-(aminosulfonyl)phenyl]amino]-N-(2,6-difluorophenyl)-1H-1,2,4-triazole-1-carboamide	IC50	3.7 nM
(2S,3R)-3-[[5-bromo-2-[3-methyl-4-(methylsulfonimidoyl)anilino]pyrimidin-4-yl]amino]butan-2-ol	IC50	4 nM	US-8507510: Sulfoximine-substituted pyrimidines as CDK- and/or VEGF inhibitors, their production and use as pharmaceutical agents
(3R)-3-[[5-bromo-2-[3-methyl-4-(methylsulfonimidoyl)anilino]pyrimidin-4-yl]amino]-2-methylbutan-2-ol	IC50	4 nM	US-8507510: Sulfoximine-substituted pyrimidines as CDK- and/or VEGF inhibitors, their production and use as pharmaceutical agents
N-[5-[[[5-(Cyclohexylmethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]acetamide	IC50	4 nM

ChEMBL bioactivities

3064 potent at pChembl≥5 of 3461 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL194540
9.62	IC50	0.24	nM	CHEMBL4289226
9.46	Ki	0.35	nM	CHEMBL5176826
9.40	IC50	0.4	nM	STAUROSPORINE
9.38	IC50	0.42	nM	CHEMBL4277525
9.37	IC50	0.43	nM	CHEMBL4279832
9.30	Ki	0.5	nM	CHEMBL2348843
9.30	IC50	0.5	nM	CHEMBL4287693
9.27	IC50	0.54	nM	CHEMBL1964259
9.22	IC50	0.6	nM	CHEMBL261720
9.22	IC50	0.6	nM	CHEMBL384350
9.22	IC50	0.6	nM	CHEMBL426509
9.15	IC50	0.7	nM	CHEMBL248713
9.15	IC50	0.7	nM	CHEMBL511394
9.10	IC50	0.8	nM	CHEMBL429478
9.10	IC50	0.8	nM	CHEMBL561334
9.05	IC50	0.9	nM	CHEMBL194721
9.02	IC50	0.96	nM	CHEMBL4287743
9.00	IC50	1	nM	CHEMBL215803
9.00	Ki	1	nM	CHEMBL2348844
9.00	IC50	1	nM	CHEMBL3897452
9.00	IC50	1	nM	CHEMBL212552
9.00	IC50	1	nM	DINACICLIB
9.00	IC50	1	nM	CHEMBL557318
9.00	IC50	1	nM	CHEMBL4281514
9.00	IC50	1	nM	CHEMBL194721
8.96	IC50	1.1	nM	CHEMBL248712
8.96	IC50	1.09	nM	CHEMBL4294940
8.89	IC50	1.3	nM	STAUROSPORINE
8.86	IC50	1.38	nM	STAUROSPORINE
8.85	IC50	1.42	nM	STAUROSPORINE
8.85	IC50	1.4	nM	XYLOCYDINE
8.82	Ki	1.5	nM	CHEMBL2348842
8.80	IC50	1.6	nM	STAUROSPORINE
8.79	IC50	1.63	nM	STAUROSPORINE
8.77	IC50	1.7	nM	STAUROSPORINE
8.76	IC50	1.74	nM	CHEMBL4284301
8.74	IC50	1.8	nM	CHEMBL3716786
8.74	IC50	1.8	nM	CHEMBL249303
8.72	IC50	1.9	nM	CHEMBL377449
8.71	IC50	1.93	nM	STAUROSPORINE
8.71	IC50	1.97	nM	STAUROSPORINE
8.70	Ki	2	nM	CHEMBL2348847
8.70	IC50	2	nM	CHEMBL192216
8.70	IC50	2	nM	CHEMBL3648115
8.70	IC50	2	nM	CHEMBL3648111
8.70	IC50	2	nM	CHEMBL3648112
8.70	IC50	2	nM	RGB-286638
8.70	IC50	2	nM	CHEMBL212299
8.70	Ki	2	nM	RG-547

PubChem BioAssay actives

2578 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-(9-nitro-6-oxo-7,12-dihydro-5H-indolo[3,2-d][1]benzazepin-2-yl)propanenitrile	1799616: Kinase Assay from Article 10.1002/cbic.200400099: “Structure-aided optimization of kinase inhibitors derived from alsterpaullone.”	ic50	0.0002	uM
3-[2-acetyl-3-(2-chlorophenyl)-3,4-dihydropyrazol-5-yl]-4-hydroxychromen-2-one	1927552: Inhibition of CDK1 (unknown origin) assessed as inhibition constant	ki	0.0003	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	262975: Inhibition of CDK1 at 10 uM ATP	ic50	0.0004	uM
N-[2-(2-hydroxyethoxy)ethyl]-4-[(7-hydroxy-6H-pyrrolo[2,3-g][1,3]benzothiazol-8-yl)methylideneamino]benzenesulfonamide	1949775: Inhibition of human CDK1 using Biotinaminohexyl-Ala-Arg-Arg-Pro-Met-Ser-Pro-Lys-LysLys-Ala-CONH2 peptide as substrate incubated for 20 to 30 mins by scintillation counter analysis	ic50	0.0005	uM
N-[2-methyl-4-(2-pyrrolidin-1-ylethyl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine	270821: Inhibition of CDK1/cyclinB by Flashplate assay	ic50	0.0006	uM
2-[3-methyl-4-[[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-yl]amino]phenyl]ethanol	270821: Inhibition of CDK1/cyclinB by Flashplate assay	ic50	0.0006	uM
5-amino-N-(2,6-difluorophenyl)-3-(4-sulfamoylanilino)-1,2,4-triazole-1-carbothioamide	1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “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.”	ic50	0.0006	uM
N-[[5-[3-(6-fluoro-1H-benzimidazol-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]methyl]ethanamine	308239: Inhibition of CDK1	ic50	0.0007	uM
N-[[5-[3-(6-fluoro-1H-benzimidazol-2-yl)-3H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]methyl]ethanamine	365550: Inhibition of CDK1/cyclinB	ic50	0.0007	uM
N-[[5-[3-(6-methoxy-1H-benzimidazol-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]methyl]ethanamine	308239: Inhibition of CDK1	ic50	0.0008	uM
(15R)-15-methyl-11-thia-6,14,17-triazatetracyclo[8.8.0.02,7.012,18]octadeca-1(10),2(7),3,5,8,12(18)-hexaen-13-one	430428: Inhibition of CDK2	ic50	0.0008	uM
2-N-(3H-benzimidazol-5-yl)-4-N-(2-chlorophenyl)-5-(trifluoromethyl)pyrimidine-2,4-diamine	240581: Inhibitory concentration against Cyclin dependent kinase 1	ic50	0.0009	uM
N-[[5-[3-(4,6-difluoro-1H-benzimidazol-2-yl)-1H-indazol-4-yl]-4-methyl-3-pyridinyl]methyl]ethanamine	1317305: Inhibition of CDK1/cyclin B (unknown origin)	ic50	0.0010	uM
(13R,15S)-13-methyl-16-oxa-8,9,12,22,24-pentazahexacyclo[15.6.2.16,9.112,15.02,7.021,25]heptacosa-1(24),2,4,6,17,19,21(25)-heptaene-23,27-dione	271346: Inhibition of CDK1	ic50	0.0010	uM
N-[2-(dimethylamino)ethyl]-2-fluoro-4-[[5-fluoro-4-(2-methyl-3-propan-2-ylimidazol-4-yl)pyrimidin-2-yl]amino]benzamide	411414: Inhibition of CDK1	ic50	0.0010	uM
N-[2-methyl-4-(2-piperidin-1-ylethyl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine	270821: Inhibition of CDK1/cyclinB by Flashplate assay	ic50	0.0010	uM
(5R)-5-methyl-14-oxa-9-thia-3,6-diazatetracyclo[8.7.0.02,8.013,17]heptadeca-1(10),2(8),11,13(17),15-pentaen-7-one	430428: Inhibition of CDK2	ic50	0.0010	uM
2-[(2S)-1-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol	1781575: Inhibition of CDK1 (unknown origin) expressed in Sf9 insect cells using biotinylated peptide derived Histone H1 as substrate incubated for 1 hr in presence of [gamma33P]ATP by liquid scintillation counter method	ic50	0.0010	uM
(3Z)-5-(2-chloroacetyl)-3-(1H-imidazol-5-ylmethylidene)-1H-indol-2-one	606558: Inhibition of human Cdk1/cyclinB using histone H1 as a substrate and [gamma-32P]ATP	ic50	0.0010	uM
(3Z)-5-(2-chloroacetyl)-3-[(5-methyl-1H-imidazol-4-yl)methylidene]-1H-indol-2-one	606558: Inhibition of human Cdk1/cyclinB using histone H1 as a substrate and [gamma-32P]ATP	ic50	0.0010	uM
N-[(3Z)-3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]prop-2-ynamide	606558: Inhibition of human Cdk1/cyclinB using histone H1 as a substrate and [gamma-32P]ATP	ic50	0.0010	uM
N-[(3Z)-3-[(5-methyl-1H-imidazol-4-yl)methylidene]-2-oxo-1H-indol-5-yl]prop-2-ynamide	606558: Inhibition of human Cdk1/cyclinB using histone H1 as a substrate and [gamma-32P]ATP	ic50	0.0010	uM
N-[[5-[3-(5,6-difluoro-1H-benzimidazol-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]methyl]ethanamine	308239: Inhibition of CDK1	ic50	0.0011	uM
N-ethyl-N-[[2-(5-isoquinolin-4-yl-2H-pyrazolo[3,4-b]pyridin-3-yl)-1H-benzimidazol-4-yl]methyl]ethanamine	308239: Inhibition of CDK1	ic50	0.0018	uM
N-[2-methyl-4-(2-morpholin-4-ylethyl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine	270821: Inhibition of CDK1/cyclinB by Flashplate assay	ic50	0.0019	uM
1-[3-[4-[[4-(2-methoxyethyl)piperazin-1-yl]methyl]phenyl]-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]-3-morpholin-4-ylurea	1317305: Inhibition of CDK1/cyclin B (unknown origin)	ic50	0.0020	uM
[4-[[5-fluoro-4-(2-methyl-3-propan-2-ylimidazol-4-yl)pyrimidin-2-yl]amino]phenyl]-[(3S)-3-(methylamino)pyrrolidin-1-yl]methanone	411414: Inhibition of CDK1	ic50	0.0020	uM
(2R,3R)-3-[5-bromo-2-[4-(ethylsulfonimidoyl)anilino]pyrimidin-4-yl]oxybutan-2-ol	1704619: Inhibition of GST-tagged recombinant human CDK1/GST-tagged human cyclin B expressed in Sf-9 cells incubated for 10 mins by scintillation counting method	ic50	0.0020	uM
N-[4-(2-methylpropoxy)-5-(trifluoromethyl)pyrimidin-2-yl]-3H-benzimidazol-5-amine	240581: Inhibitory concentration against Cyclin dependent kinase 1	ic50	0.0020	uM
4-N-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-yl]cyclohexane-1,4-diamine	270821: Inhibition of CDK1/cyclinB by Flashplate assay	ic50	0.0020	uM
4-[[5-amino-1-(3-fluorothiophene-2-carbonyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “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.”	ic50	0.0021	uM
N-[[5-[3-(4,6-difluoro-1H-benzimidazol-2-yl)-1H-indazol-5-yl]-4-methyl-3-pyridinyl]methyl]ethanamine	1549287: Inhibition of CDK1/Cyclin B (unknown origin) using histone H1 as substrate in presence of gamma[32P] ATP by phosphorimaging analysis	ic50	0.0023	uM
1-[5-[3-[4-(methoxymethyl)-1H-benzimidazol-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]-N-methylmethanamine	308239: Inhibition of CDK1	ic50	0.0025	uM
2-hydroxy-3-[(4-sulfamoylphenyl)diazenyl]-1H-indole-5-carboxamide	1326908: Inhibition of human CDK1/cyclinA expressed in Baculovirus infected Sf9 cells using Biotin-aminohexyl-Ala-Arg-Arg-Pro-Met-Ser-Pro-Lys-LysLys-Ala-CONH2 as substrate measured after 30 to 60 mins in presence of [gamma-32P]ATP by scintillation counting method	ic50	0.0028	uM
3,4-dimethyl-5-[2-(4-methyl-3-nitroanilino)pyrimidin-4-yl]-1,3-thiazol-2-one	1799550: In Vitro Kinase Assay from Article 10.1016/j.chembiol.2010.07.016: “Discovery and characterization of 2-anilino-4- (thiazol-5-yl)pyrimidine transcriptional CDK inhibitors as anticancer agents.”	ki	0.0030	uM
N-[[5-[3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]methyl]ethanamine	308239: Inhibition of CDK1	ic50	0.0030	uM
2-[(2R)-1-[3-methyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol	1424514: Inhibition of recombinant CDK1 (unknown origin) expressed in Sf9 cells using histone H1 derived biotinylated peptide and 33P-ATP incubated for 1 hr by liquid scintillation counting method	ic50	0.0030	uM
(16E)-14-methyl-20-oxa-5,7,14,27-tetrazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2(27),3,5,8,10,12(26),16,21,23-decaene	1317349: Inhibition of CDK1 (unknown origin)	ic50	0.0030	uM
2-[(1S)-2-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]cyclohexyl]ethanol	1890153: Inhibition of recombinant CDK1 (unknown origin) expressed in baculovirus infected Sf9 insect cells using biotinylated-histone H1 as substrate incubated for 1 hr in presence of 33P-ATP by liquid scintillation counter method	ic50	0.0030	uM
4-[[1-(2,6-difluoro-3-methylbenzoyl)-5-methyl-1,2,4-triazol-3-yl]amino]benzenesulfonamide	241014: Inhibition of Cyclin B-cyclin-dependent kinase 1	ic50	0.0030	uM
2-N-(3H-benzimidazol-5-yl)-4-N-(3-chlorophenyl)-5-(trifluoromethyl)pyrimidine-2,4-diamine	240581: Inhibitory concentration against Cyclin dependent kinase 1	ic50	0.0030	uM
N-(2-methylphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine	270821: Inhibition of CDK1/cyclinB by Flashplate assay	ic50	0.0030	uM
N-(2-aminoethyl)-N-[5-[(1-cycloheptylpyrazolo[3,4-d]pyrimidin-6-yl)amino]-2-pyridinyl]methanesulfonamide	617336: Inhibition of CDK1/Cyclin B assessed as phosphorylation of Z-lyte Peptide at 0.017 to 30 nM by FRET assay	ic50	0.0030	uM
4-[[5-methyl-1-(2,3,6-trifluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	241014: Inhibition of Cyclin B-cyclin-dependent kinase 1	ic50	0.0032	uM
4-[[5-amino-2-(2,6-difluorobenzenecarbothioyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	241014: Inhibition of Cyclin B-cyclin-dependent kinase 1	ic50	0.0032	uM
N-[5-amino-1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-5-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-2-methylbenzamide	578724: Inhibition of CDK1/cyclin B	ic50	0.0032	uM
4-[[5-amino-1-(2,3,6-trifluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “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.”	ic50	0.0032	uM
4-[[5-amino-1-(3,5-dimethylthiophene-2-carbonyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “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.”	ic50	0.0032	uM
3-amino-N-(2,6-difluorophenyl)-5-(4-sulfamoylanilino)-1,2,4-triazole-1-carbothioamide	1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “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.”	ic50	0.0032	uM
5-amino-N-(2,6-difluorophenyl)-3-(4-sulfamoylanilino)-1,2,4-triazole-1-carboxamide	1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “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.”	ic50	0.0037	uM

CTD chemical–gene interactions

382 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	affects cotreatment, affects binding, increases reaction, decreases expression, decreases activity (+5 more)	11
bisphenol A	affects expression, decreases expression, increases expression, increases phosphorylation, decreases reaction (+1 more)	10
sodium arsenite	decreases phosphorylation, increases expression, increases phosphorylation, decreases reaction, affects expression (+2 more)	9
Resveratrol	decreases activity, decreases expression, decreases reaction, affects activity, affects expression (+5 more)	9
ochratoxin A	affects binding, affects reaction, decreases phosphorylation, increases expression, decreases reaction (+3 more)	6
alvocidib	affects cotreatment, decreases activity, decreases expression	6
Arsenic Trioxide	decreases activity, affects expression, affects cotreatment, affects binding, increases reaction (+4 more)	6
Cisplatin	decreases reaction, affects reaction, decreases activity, increases phosphorylation, affects phosphorylation (+3 more)	6
Paclitaxel	increases expression, increases phosphorylation, affects reaction, increases reaction, decreases expression (+5 more)	6
Cadmium Chloride	decreases reaction, increases expression, decreases expression, increases abundance, increases phosphorylation (+2 more)	6
Benzo(a)pyrene	affects localization, decreases expression, increases expression	5
Estradiol	increases reaction, decreases reaction, decreases expression, increases expression	5
Fluorouracil	affects expression, decreases expression, increases expression, affects cotreatment	5
Quercetin	decreases expression, decreases phosphorylation	5
Tetrachlorodibenzodioxin	increases reaction, decreases expression, increases expression, decreases reaction, increases phosphorylation	5
Tretinoin	affects reaction, increases expression, decreases expression	5
Genistein	decreases activity, decreases reaction, increases phosphorylation, affects expression, decreases phosphorylation (+1 more)	5
trichostatin A	decreases reaction, increases expression, increases reaction, decreases expression	4
diallyl trisulfide	affects binding, increases reaction, decreases activity, decreases expression, increases phosphorylation (+1 more)	4
2-((((2-chloroethyl)nitrosoamino)carbonyl)amino)propanamide	decreases activity, decreases expression, increases expression, increases phosphorylation	4
(+)-JQ1 compound	decreases expression	4
Bortezomib	decreases activity, increases phosphorylation, decreases reaction, increases activity	4
Cadmium	increases abundance, increases expression, decreases expression, decreases reaction, affects binding (+1 more)	4
Sirolimus	affects cotreatment, decreases expression, decreases phosphorylation	4
Particulate Matter	affects expression, increases expression, decreases expression, increases abundance	4
methylselenic acid	affects reaction, decreases expression	3
arsenite	decreases activity, decreases reaction, decreases expression	3
perfluorooctanoic acid	affects cotreatment, affects expression, decreases expression	3
tanespimycin	affects expression, affects reaction, affects cotreatment, decreases expression	3
Oxaliplatin	decreases expression, increases expression	3

ChEMBL screening assays

1262 unique, capped per target: 1242 binding, 11 admet, 8 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000364	Binding	Inhibition of Cdc2/cyclin B assessed as inhibition of histone H1 phosphorylation in human HT29 cells	Synthesis and structure-activity relationships of N-6 substituted analogues of 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of Wee1 and Chk1 checkpoint kinases. — Eur J Med Chem
CHEMBL4004950	ADMET	Inhibition of recombinant human CDK1/Cyclin B expressed in baculovirus infected Sf9 cells at using PKTPKKAKKL-NH2 as substrate relative to untreated control	Cyclin-Dependent Kinase (CDK) Inhibitors: Structure-Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines. — J Med Chem
CHEMBL700201	Functional	In vitro antiproliferative activity against myeloid leukemia K562 cell line	Pyrazolo[4,3-d]pyrimidines as new generation of cyclin-dependent kinase inhibitors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.