CDK2

Summary

CDK2 (cyclin dependent kinase 2, HGNC:1771) is a protein-coding gene on chromosome 12q13.2, encoding Cyclin-dependent kinase 2 (P24941). Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. It is a selective cancer dependency (DepMap: 71.1% of cell lines).

This gene encodes a member of a family of serine/threonine protein kinases that participate in cell cycle regulation. The encoded protein is the catalytic subunit of the cyclin-dependent protein kinase complex, which regulates progression through the cell cycle. Activity of this protein is especially critical during the G1 to S phase transition. This protein associates with and regulated by other subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A), and p27Kip1 (CDKN1B). Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1017 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 19 total
• Druggable target: yes — 85 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 71.1% of screened cell lines
• MANE Select transcript: NM_001798

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1771
Approved symbol	CDK2
Name	cyclin dependent kinase 2
Location	12q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000123374
Ensembl biotype	protein_coding
OMIM	116953
Entrez	1017

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding_CDS_not_defined, 4 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000266970, ENST00000354056, ENST00000440311, ENST00000553376, ENST00000554545, ENST00000554619, ENST00000555357, ENST00000555408, ENST00000556146, ENST00000556276, ENST00000556464, ENST00000556656

RefSeq mRNA: 3 — MANE Select: NM_001798 NM_001290230, NM_001798, NM_052827

CCDS: CCDS76567, CCDS8898, CCDS8899

Canonical transcript exons

ENST00000266970 — 7 exons

Exon	Start	End
ENSE00001215687	55971521	55972789
ENSE00002260310	55966830	55967124
ENSE00003566576	55971044	55971247
ENSE00003600826	55968778	55968948
ENSE00003639718	55969475	55969576
ENSE00003656909	55967857	55967934
ENSE00003659990	55968049	55968169

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 96.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.5364 / max 483.2034, expressed in 1803 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126015	19.8719	1743
126014	9.4387	1699
126013	1.5859	895
126016	1.2428	388
126020	0.1284	35
126012	0.1115	46
126017	0.0588	24
126018	0.0567	25
126019	0.0417	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	96.02	gold quality
ganglionic eminence	UBERON:0004023	95.40	gold quality
embryo	UBERON:0000922	93.75	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.57	gold quality
lower esophagus	UBERON:0013473	91.54	gold quality
left uterine tube	UBERON:0001303	90.84	gold quality
mucosa of stomach	UBERON:0001199	90.67	gold quality
stromal cell of endometrium	CL:0002255	90.38	gold quality
skin of abdomen	UBERON:0001416	90.15	gold quality
left ovary	UBERON:0002119	90.04	gold quality
skin of leg	UBERON:0001511	89.75	gold quality
right lung	UBERON:0002167	89.71	gold quality
colonic epithelium	UBERON:0000397	89.52	gold quality
placenta	UBERON:0001987	89.36	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.35	gold quality
right ovary	UBERON:0002118	89.32	gold quality
cartilage tissue	UBERON:0002418	89.27	gold quality
esophagus	UBERON:0001043	89.13	gold quality
upper lobe of left lung	UBERON:0008952	89.06	gold quality
rectum	UBERON:0001052	88.91	gold quality
vermiform appendix	UBERON:0001154	88.76	gold quality
descending thoracic aorta	UBERON:0002345	88.61	gold quality
upper lobe of lung	UBERON:0008948	88.50	gold quality
zone of skin	UBERON:0000014	88.31	gold quality
endocervix	UBERON:0000458	88.23	gold quality
body of uterus	UBERON:0009853	88.09	gold quality
ectocervix	UBERON:0012249	88.03	gold quality
gall bladder	UBERON:0002110	87.91	gold quality
omental fat pad	UBERON:0010414	87.90	gold quality
peritoneum	UBERON:0002358	87.84	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-23	yes	317.57
E-GEOD-93593	yes	14.01
E-ANND-3	yes	7.38

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARNT, CEBPA, CUX1, DDIT3, E2F1, E2F3, E2F4, FOSB, GLI1, HINFP, IRF1, IRF2, IRF3, JUND, KAT2B, LRRC4, MAFK, MITF, MYBL2, MYC, MYOD1, NCOA1, NFKB, NR2F2, SP1, TFDP1, TP53, ZBTB7A, ZEB1, ZNF699

miRNA regulators (miRDB)

76 targeting CDK2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-6794-5P	99.76	66.38	1048

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 71.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Cyclin A/Cdk2 and cyclin E/cdk2 continuously shuttle between the nucleus and the cytoplasm (PMID:11907280)
• results argue that TTK-associated CDK2 may function to maintain target-specific phosphorylation of RNA Pol II that is essential for Tat transactivation of HIV-1 promoter (PMID:12049628)
• Activation mechanism role of cyclin binding versus phosphorylation (PMID:12081504)
• CDK2/cyclin E is required for Tat-dependent transcription in vitro. (PMID:12114499)
• CDK2 binding to cyclin E is required to drive cells from G(1) into S phase (PMID:12149264)
• Interferon gamma reduces the activity of Cdk4 and Cdk2, inhibiting he G1 cell cycle in human hepatocellular carcinoma cells. (PMID:12531694)
• CDK2 is not required for sustained cell division. (PMID:12676582)
• Data suggest that the interaction between PKCeta and cyclin E is carefully regulated, and is correlated with the inactivated form of the cyclin E/Cdk2 complex. (PMID:12729791)
• IRF1 represses CDK2 gene expression by interfering with SP1-dependent transcriptional activation. (PMID:12732645)
• role in regulating Cdc25A half life (PMID:12801928)
• TGF-beta 1 inhibition requires early G(1) induction and stabilization of p21 protein, which binds to & inhibits cyclin E-CDK2 and cyclin A-CDK2 kinase activity rather than direct modulation of cyclin or CDK protein levels as seen in other systems. (PMID:12810668)
• Cdk2 has a role in phosphorylation of the NF-Y transcription factor (PMID:12857729)
• CDK2 has a role in the G2 DNA damage checkpoint (PMID:12912980)
• Kaposi’s sarcoma-associated herpesvirus K-bZIP physically associates with cyclin-CDK2 and downmodulates its kinase activity. (PMID:12915577)
• it is evident that B-Myb protein may promote cell proliferation by a non-transcriptional mechanism that involves release of active cyclin/cyclin dependent kinase 2 from cyclin-dependent inhibitor 1C p57(KIP2) (PMID:12947099)
• Inhibition of Cdk2 by 1,25-(OH)2D3 may thus involve two mechanisms: 1) reduced nuclear Cdk2 available for cyclin binding and activation and 2) impairment of cyclin E-Cdk2-dependent p27 degradation through cytoplasmic mislocalization of Cdk2. (PMID:12954644)
• kinetic insight into the basis for selecting suboptimal specificity determinants for the phosphorylation of cellular substrates (PMID:14506259)
• multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation (PMID:14536078)
• CDK2 binds to SU9516 at Leu83 and Glu81 (PMID:14550307)
• CDK2 activation process through phosphorylation is examined using 2D PAGE (PMID:14551212)
• Epstein-Barr virus can inhibit genotoxin-induced G1 arrest downstream of p53 by preventing the inactivation of CDK2 (PMID:14562046)
• p220 is an essential downstream component of the cyclin E/Cdk2 signaling pathway and functions to coordinate multiple elements of the G1/S transition. (PMID:14612403)
• CDK2-cyclin E, without prior CDK4-cyclin D activity, can phosphorylate and inactivate pRb, activate E2F, and induce DNA synthesis. (PMID:14645251)
• significant difference in their biochemical properties between CDK4/cyclin D1 and CDK2/cyclin A affecting regulation of cellular RB function (PMID:14646596)
• cyclin-dependent kinase (CDK)2, -4, and -6 were down-regulated from the myelocytes/metamyelocytes stages and onward (PMID:14694185)
• CDK2 complexes have roles in G(1)/S deregulation and tumor progression (PMID:14701826)
• CDK2 regulates beta-catenin phosphorylation/ degradation (PMID:14985333)
• Cdk2 and Cdk4 phosphorylate human Cdt1 and induce its degradation (PMID:15004027)
• Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic data suggest a sequential mechanism that is initiated by binding to cyclin A (PMID:15024385)
• We also found that cyclin A/CDK2 phosphorylates Axin, thereby enhancing its association with beta-catenin. (PMID:15063782)
• study provides evidence that the cyclin A1-cyclin dependent kinase 2 complex plays a role in several signaling pathways important for cell cycle control and meiosis (PMID:15159402)
• interacts with dephosphorylated NIRF (PMID:15178429)
• cyclin A-cdk2 plays an ancillary noncatalytic role in the ubiquitination of p27(KIP1) by the SCF(skp2) complex (PMID:15199159)
• Results identify an important role for CDK2 in the maintenance of genomic stability, acting via an ATM- and ATR-dependent pathway. (PMID:15226429)
• after CDK4/6 inactivation, the fate of pancreatic tumor cells depends on the ability to modulate CDK2 activity (PMID:15309028)
• Data suggest that cyclin D1-Cdk2 complexes mediate some of the transforming effects of cyclin D1 and demonstrate that the cyclin D1-Cdk2 fusion protein is a useful model to investigate the biological functions of cyclin D1-Cdk2 complexes. (PMID:15355984)
• These findings establish a novel function for cyclin A1 and CDK2 in DNA double strand break repair following radiation damage. (PMID:15456866)
• Phosphborylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of CDK2. (PMID:15572662)
• cyclin A/Cdk2 has a role as a progesterone receptor coactivator (PMID:15601848)
• CDK2 depletion suppressed growth and cell cycle progression in melanoma and may be a suitable drug target in melanoma. (PMID:15607961)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdk2	ENSDARG00000026577
mus_musculus	Cdk2	ENSMUSG00000025358
rattus_norvegicus	Cdk2	ENSRNOG00000006469

Paralogs (26): CDKL3 (ENSG00000006837), CDKL5 (ENSG00000008086), CDK11A (ENSG00000008128), CDK14 (ENSG00000058091), CDK17 (ENSG00000059758), CDK13 (ENSG00000065883), CDKL1 (ENSG00000100490), CDK16 (ENSG00000102225), CDK6 (ENSG00000105810), PRP4K (ENSG00000112739), CDK18 (ENSG00000117266), CDK8 (ENSG00000132964), CDK7 (ENSG00000134058), CDK4 (ENSG00000135446), CDK9 (ENSG00000136807), CDK15 (ENSG00000138395), CDKL2 (ENSG00000138769), CDK19 (ENSG00000155111), CDK20 (ENSG00000156345), CDK5 (ENSG00000164885), CDK12 (ENSG00000167258), CDK1 (ENSG00000170312), CDK10 (ENSG00000185324), CDKL4 (ENSG00000205111), CDK11B (ENSG00000248333), CDK3 (ENSG00000250506)

Protein

Protein identifiers

Cyclin-dependent kinase 2 — P24941 (reviewed: P24941)

Alternative names: Cell division protein kinase 2, p33 protein kinase

All UniProt accessions (4): E7ESI2, P24941, G3V317, G3V5T9

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CABLES1, CTNNB1, CDK2AP2, ERCC6, NBN, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, SUV39H1, EZH2. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in embryonic stem cells (ESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Involved in regulation of telomere repair by mediating phosphorylation of NBN. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability. Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks. Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of the C-terminus of protein kinase B (PKB/AKT1 and PKB/AKT2), promoting its activation.

Subunit / interactions. Found in a complex with CABLES1, CCNA1 and CCNE1. Interacts with CABLES1. Interacts with UHRF2. Part of a complex consisting of UHRF2, CDK2 and CCNE1. Interacts with the Speedy/Ringo proteins SPDYA and SPDYC. Interaction with SPDYA promotes kinase activation via a conformation change that alleviates obstruction of the substrate-binding cleft by the T-loop. Found in a complex with both SPDYA and CDKN1B/KIP1. Binds to RB1 and CDK7. Binding to CDKN1A (p21) leads to CDK2/cyclin E inactivation at the G1-S phase DNA damage checkpoint, thereby arresting cells at the G1-S transition during DNA repair. Associated with PTPN6 and beta-catenin/CTNNB1. Interacts with CACUL1. May interact with CEP63. Interacts with ANKRD17. Interacts with CEBPA (when phosphorylated). Forms a ternary complex with CCNA2 and CDKN1B; CDKN1B inhibits the kinase activity of CDK2 through conformational rearrangements. Interacts with cyclins A, B1, B3, D, or E. Interacts with CDK2AP2.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Nucleus. Cajal body. Endosome.

Post-translational modifications. Phosphorylated at Thr-160 by CDK7 in a CAK complex. Phosphorylation at Thr-160 promotes kinase activity, whereas phosphorylation at Tyr-15 by WEE1 reduces slightly kinase activity. Phosphorylated on Thr-14 and Tyr-15 during S and G2 phases before being dephosphorylated by CDC25A. Nitrosylated after treatment with nitric oxide (DETA-NO).

Activity regulation. Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it. Inhibited by 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), AG-024322, N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), R547 (Ro-4584820), purine, pyrimidine and pyridine derivatives, 2-aminopyrimidines, paullones, thiazo derivatives, macrocyclic quinoxalin-2-one, pyrazolo[1,5-a]-1,3,5-triazine, pyrazolo[1,5-a]pyrimidine, 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine, seliciclib and CYC202), SNS-032 (BMS-387032), triazolo[1,5-a]pyrimidines, staurosporine and olomoucine. Stimulated by MYC. Inactivated by CDKN1A (p21).

Cofactor. Binds 2 Mg(2+) ions.

Induction. Induced transiently by TGFB1 at an early phase of TGFB1-mediated apoptosis.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P24941-1	1	yes
P24941-2	2, CDK2deltaT

RefSeq proteins (3): NP_001277159, NP_001789, NP_439892 (=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), 2 shown:

• 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 (72 total): helix 16, strand 14, binding site 8, mutagenesis site 7, modified residue 6, turn 6, sequence variant 4, sequence conflict 4, site 3, chain 1, domain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

521 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6Q4G	X-RAY DIFFRACTION	0.98
6Q49	X-RAY DIFFRACTION	1
6Q4H	X-RAY DIFFRACTION	1
6Q48	X-RAY DIFFRACTION	1.03
6Q4J	X-RAY DIFFRACTION	1.05
6Q4E	X-RAY DIFFRACTION	1.06
6Q4K	X-RAY DIFFRACTION	1.06
6Q4D	X-RAY DIFFRACTION	1.07
6Q3B	X-RAY DIFFRACTION	1.11
6Q4I	X-RAY DIFFRACTION	1.11
6Q4B	X-RAY DIFFRACTION	1.12
6Q4A	X-RAY DIFFRACTION	1.13
9GNO	X-RAY DIFFRACTION	1.16
6Q3F	X-RAY DIFFRACTION	1.18
6Q4F	X-RAY DIFFRACTION	1.21
4EK4	X-RAY DIFFRACTION	1.26
4FKL	X-RAY DIFFRACTION	1.26
2R3I	X-RAY DIFFRACTION	1.28
6Q3C	X-RAY DIFFRACTION	1.29
1GZ8	X-RAY DIFFRACTION	1.3
5MHQ	X-RAY DIFFRACTION	1.3
6GUK	X-RAY DIFFRACTION	1.3
8ERD	X-RAY DIFFRACTION	1.33
4EK3	X-RAY DIFFRACTION	1.34
2R3Q	X-RAY DIFFRACTION	1.35
7RXO	X-RAY DIFFRACTION	1.38
7ZPC	X-RAY DIFFRACTION	1.4
4GCJ	X-RAY DIFFRACTION	1.42
2R3R	X-RAY DIFFRACTION	1.47
4FKU	X-RAY DIFFRACTION	1.47

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P24941-F1	88.55	0.69

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 (4): 9 (cdk7 binding); 88–89 (cdk7 binding); 166 (cdk7 binding); 127 (proton acceptor)

Ligand- & substrate-binding residues (8): 145; 10–18; 33; 81–83; 86; 129–132; 132; 145

Post-translational modifications (6): 1, 6, 14, 15, 19, 160

Mutagenesis-validated functional residues (7):

Position	Phenotype
9	reduced phosphorylation by cak.
14	2-fold increase in activity.
15	2-fold increase in activity.
88–89	reduced phosphorylation by cak.
145	dominant negative kinase dead mutant.
160	abolishes activity.
166	reduced phosphorylation by cak and reduced kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

75 pathways

ID	Pathway
R-HSA-1538133	G0 and Early G1
R-HSA-171319	Telomere Extension By Telomerase
R-HSA-176187	Activation of ATR in response to replication stress
R-HSA-176408	Regulation of APC/C activators between G1/S and early anaphase
R-HSA-187577	SCF(Skp2)-mediated degradation of p27/p21
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2559586	DNA Damage/Telomere Stress Induced Senescence
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-6804116	TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-6804757	Regulation of TP53 Degradation
R-HSA-68911	G2 Phase
R-HSA-68949	Orc1 removal from chromatin
R-HSA-68962	Activation of the pre-replicative complex
R-HSA-69017	CDK-mediated phosphorylation and removal of Cdc6
R-HSA-69200	Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes
R-HSA-69202	Cyclin E associated events during G1/S transition
R-HSA-69231	Cyclin D associated events in G1
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-69563	p53-Dependent G1 DNA Damage Response
R-HSA-69656	Cyclin A:Cdk2-associated events at S phase entry
R-HSA-8849470	PTK6 Regulates Cell Cycle
R-HSA-912446	Meiotic recombination
R-HSA-9616222	Transcriptional regulation of granulopoiesis
R-HSA-9661069	Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)
R-HSA-9825892	Regulation of MITF-M-dependent genes involved in cell cycle and proliferation
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-109582	Hemostasis
R-HSA-1266738	Developmental Biology
R-HSA-1474165	Reproduction

MSigDB gene sets: 565 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, REACTOME_MEIOTIC_RECOMBINATION, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_DNA_REPLICATION, MODULE_52, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, CCAWYNNGAAR_UNKNOWN, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_ANAPHASE_PROMOTING_COMPLEX_DEPENDENT_CATABOLIC_PROCESS, REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21, GOBP_PEPTIDYL_SERINE_MODIFICATION

GO Biological Process (35): G1/S transition of mitotic cell cycle (GO:0000082), G2/M transition of mitotic cell cycle (GO:0000086), negative regulation of transcription by RNA polymerase II (GO:0000122), DNA replication (GO:0006260), DNA repair (GO:0006281), chromatin remodeling (GO:0006338), DNA-templated transcription (GO:0006351), protein phosphorylation (GO:0006468), potassium ion transport (GO:0006813), centriole replication (GO:0007099), signal transduction (GO:0007165), Ras protein signal transduction (GO:0007265), regulation of mitotic cell cycle (GO:0007346), positive regulation of cell population proliferation (GO:0008284), regulation of G2/M transition of mitotic cell cycle (GO:0010389), regulation of gene expression (GO:0010468), peptidyl-serine phosphorylation (GO:0018105), positive regulation of heterochromatin formation (GO:0031453), mitotic G1 DNA damage checkpoint signaling (GO:0031571), positive regulation of DNA-templated DNA replication initiation (GO:0032298), telomere maintenance in response to DNA damage (GO:0043247), post-translational protein modification (GO:0043687), positive regulation of DNA replication (GO:0045740), positive regulation of DNA-templated transcription (GO:0045893), centrosome duplication (GO:0051298), cell division (GO:0051301), meiotic cell cycle (GO:0051321), cellular response to nitric oxide (GO:0071732), cellular senescence (GO:0090398), negative regulation of protein localization to chromatin (GO:0120186), regulation of heterochromatin organization (GO:0120261), regulation of anaphase-promoting complex-dependent catabolic process (GO:1905784), telomere maintenance (GO:0000723), DNA damage response (GO:0006974), protection from non-homologous end joining at telomere (GO:0031848)

GO Molecular Function (15): magnesium ion binding (GO:0000287), protein serine/threonine kinase activity (GO:0004674), cyclin-dependent protein serine/threonine kinase activity (GO:0004693), ATP binding (GO:0005524), protein domain specific binding (GO:0019904), cyclin binding (GO:0030332), cyclin-dependent protein kinase activity (GO:0097472), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), histone kinase activity (GO:0035173), metal ion binding (GO:0046872)

GO Cellular Component (21): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), chromosome, telomeric region (GO:0000781), condensed chromosome (GO:0000793), X chromosome (GO:0000805), Y chromosome (GO:0000806), male germ cell nucleus (GO:0001673), nucleus (GO:0005634), nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), endosome (GO:0005768), centrosome (GO:0005813), cytosol (GO:0005829), Cajal body (GO:0015030), cyclin A1-CDK2 complex (GO:0097123), cyclin A2-CDK2 complex (GO:0097124), cyclin E1-CDK2 complex (GO:0097134), cyclin E2-CDK2 complex (GO:0097135), cytoskeleton (GO:0005856), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
Cyclin E associated events during G1/S transition	2
Cellular Senescence	2
Switching of origins to a post-replicative state	2
G1/S Transition	2
Mitotic G1 phase and G1/S transition	1
Extension of Telomeres	1
G2/M Checkpoints	1
APC/C-mediated degradation of cell cycle proteins	1
Cyclin A:Cdk2-associated events at S phase entry	1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
TP53 Regulates Transcription of Cell Cycle Genes	1
Regulation of TP53 Activity	1
Regulation of TP53 Expression and Degradation	1
Mitotic G2-G2/M phases	1
DNA Replication Pre-Initiation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	4
cyclin-dependent protein kinase holoenzyme complex	4
mitotic cell cycle	3
cellular anatomical structure	3
mitotic cell cycle phase transition	2
DNA metabolic process	2
gene expression	2
regulation of cell cycle	2
protein binding	2
sex chromosome	2
endomembrane system	2
cell cycle G1/S phase transition	1
cell cycle G2/M phase transition	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA biosynthetic process	1
DNA damage response	1
chromatin organization	1
RNA biosynthetic process	1
phosphorylation	1
protein modification process	1
metal ion transport	1
cell cycle process	1
centrosome duplication	1
centriole assembly	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
small GTPase-mediated signal transduction	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
G2/M transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G2/M phase transition	1
regulation of macromolecule biosynthetic process	1
protein phosphorylation	1

Protein interactions and networks

STRING

7212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK2	CDKN1B	P46527	999
CDK2	CCNA1	P78396	999
CDK2	CCNE1	P24864	999
CDK2	CCNA2	P20248	999
CDK2	CDKN1A	P38936	999
CDK2	CCNL2	Q96S94	999
CDK2	CCND1	P24385	998
CDK2	CCNE2	O96020	997
CDK2	FOXO3	O43524	995
CDK2	CCNB1	P14635	993
CDK2	CDKN2A	P42771	993
CDK2	SKP2	Q13309	992
CDK2	CKS1B	P33551	990
CDK2	CDKN3	Q16667	984
CDK2	CDK4	P11802	983

IntAct

392 interactions, top by confidence:

A	B	Type	Score
CCNA2	CDK2	psi-mi:“MI:0915”(physical association)	0.980
CCNA2	CDK2	psi-mi:“MI:0407”(direct interaction)	0.980
CDK2	CCNA2	psi-mi:“MI:0407”(direct interaction)	0.980
CDK2	CDKN1A	psi-mi:“MI:0915”(physical association)	0.980
CDKN1A	CDK2	psi-mi:“MI:0915”(physical association)	0.980
CCNA2	CDK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.980
CDK2	CDKN1A	psi-mi:“MI:0407”(direct interaction)	0.980
CDK2	CDKN1A	psi-mi:“MI:0914”(association)	0.980
CDKN1A	CDK2	psi-mi:“MI:0914”(association)	0.980

BioGRID (1632): MAPT (Biochemical Activity), ESR1 (Biochemical Activity), ESR1 (Affinity Capture-Western), RB1 (Biochemical Activity), HIST1H1A (Biochemical Activity), RB1 (Biochemical Activity), CCNE1 (Biochemical Activity), E2f5 (Biochemical Activity), HIST1H1A (Biochemical Activity), E2F1 (Biochemical Activity), SCN5A (Biochemical Activity), HIST1H2AB (Biochemical Activity), HIST1H2BB (Biochemical Activity), HIST1H1A (Biochemical Activity), CDKN1B (Reconstituted Complex)

ESM2 similar proteins: O55076, O74456, O96821, P06493, P11440, P13863, P23111, P23437, P24033, P24100, P24923, P24941, P29618, P29619, P34112, P34117, P35567, P39951, P43450, P48609, P48734, P48963, P49615, P51166, P51958, P52389, P93101, Q00526, Q00535, Q02399, Q03114, Q05006, Q07785, Q26671, Q27032, Q2PQN9, Q38772, Q38773, Q41639, Q4Y4B1

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
CDK2	“down-regulates activity”	MCM4	phosphorylation
CDK2	“up-regulates activity”	LIG1	phosphorylation
CDK2	down-regulates	RBL2	phosphorylation
CDK2	unknown	RBL2	phosphorylation
CDK2	“up-regulates activity”	HIRA	phosphorylation
CDK2	up-regulates	ORC2	phosphorylation
CDK2	up-regulates	UBE2A	phosphorylation
CDK2	down-regulates	CCNE1	phosphorylation
CDK20	up-regulates	CDK2	phosphorylation
CDK2	“up-regulates activity”	TP53	phosphorylation
PTP4A1	up-regulates	CDK2
PTP4A2	up-regulates	CDK2	dephosphorylation
CDK2	down-regulates	TK1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 114 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
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	9	70.5×	1e-13
TP53 Regulates Transcription of Cell Cycle Genes	8	53.7×	4e-11
G1 Phase	10	48.6×	3e-13
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	5	44.1×	2e-06
p53-Dependent G1 DNA Damage Response	5	44.1×	2e-06
p53-Dependent G1/S DNA damage checkpoint	5	44.1×	2e-06
G1/S DNA Damage Checkpoints	5	41.5×	2e-06
Cyclin D associated events in G1	14	40.3×	4e-17

GO biological processes:

GO term	Partners	Fold	FDR
G1/S transition of mitotic cell cycle	16	30.9×	2e-17
positive regulation of G2/M transition of mitotic cell cycle	5	28.9×	1e-04
positive regulation of DNA replication	5	27.9×	1e-04
positive regulation of G1/S transition of mitotic cell cycle	6	23.1×	6e-05
G2/M transition of mitotic cell cycle	6	18.0×	1e-04
regulation of mitotic cell cycle	6	13.9×	5e-04
cell division	26	11.5×	9e-18

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

837 predictions. Top by Δscore:

Variant	Effect	Δscore
12:55967120:GACAC:G	donor_gain	1.0000
12:55967123:ACGT:A	donor_loss	1.0000
12:55967124:CGT:C	donor_loss	1.0000
12:55967125:G:GG	donor_gain	1.0000
12:55967126:TGAGT:T	donor_loss	1.0000
12:55967127:GAGTG:G	donor_loss	1.0000
12:55967836:T:TA	acceptor_gain	1.0000
12:55967845:A:AG	acceptor_gain	1.0000
12:55967846:A:AG	acceptor_gain	1.0000
12:55967854:A:AG	acceptor_gain	1.0000
12:55967854:AAGT:A	acceptor_gain	1.0000
12:55967855:A:G	acceptor_gain	1.0000
12:55967856:G:GG	acceptor_gain	1.0000
12:55967856:GT:G	acceptor_gain	1.0000
12:55967935:G:GG	donor_gain	1.0000
12:55968046:TA:T	acceptor_loss	1.0000
12:55968047:A:AG	acceptor_gain	1.0000
12:55968047:AG:A	acceptor_gain	1.0000
12:55968047:AGGCT:A	acceptor_gain	1.0000
12:55968048:G:GG	acceptor_gain	1.0000
12:55968048:GG:G	acceptor_gain	1.0000
12:55968048:GGC:G	acceptor_gain	1.0000
12:55968048:GGCT:G	acceptor_gain	1.0000
12:55968048:GGCTG:G	acceptor_gain	1.0000
12:55968166:CAAGG:C	donor_loss	1.0000
12:55968168:AGGT:A	donor_loss	1.0000
12:55968170:G:GC	donor_loss	1.0000
12:55968774:TCA:T	acceptor_loss	1.0000
12:55968776:A:AG	acceptor_gain	1.0000
12:55968776:AG:A	acceptor_loss	1.0000

AlphaMissense

1930 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:55967040:G:A	G11E	1.000
12:55967045:G:A	G13S	1.000
12:55967045:G:C	G13R	1.000
12:55967045:G:T	G13C	1.000
12:55967046:G:A	G13D	1.000
12:55967054:G:A	G16R	1.000
12:55967054:G:C	G16R	1.000
12:55967055:G:A	G16E	1.000
12:55967055:G:T	G16V	1.000
12:55967060:G:A	V18M	1.000
12:55967100:C:A	A31E	1.000
12:55967103:T:C	L32P	1.000
12:55967105:A:C	K33Q	1.000
12:55967105:A:G	K33E	1.000
12:55967106:A:T	K33M	1.000
12:55967107:G:C	K33N	1.000
12:55967107:G:T	K33N	1.000
12:55967867:G:C	G43R	1.000
12:55967867:G:T	G43C	1.000
12:55967883:C:A	A48D	1.000
12:55967886:T:A	I49N	1.000
12:55967889:G:C	R50P	1.000
12:55967891:G:A	E51K	1.000
12:55967892:A:T	E51V	1.000
12:55967893:G:C	E51D	1.000
12:55967893:G:T	E51D	1.000
12:55967897:T:C	S53P	1.000
12:55967901:T:C	L54P	1.000
12:55967904:T:C	L55P	1.000
12:55967931:T:A	V64D	1.000

dbSNP variants (sampled 300 via entrez): RS1000506207 (12:55967895 T>C), RS1000568856 (12:55972446 T>C,G), RS1001293184 (12:55966775 G>A,C,T), RS1001728800 (12:55972321 T>C), RS1002238177 (12:55965675 G>A), RS1002329912 (12:55968053 C>T), RS1003350891 (12:55970363 G>A), RS1004841408 (12:55966855 A>G,T), RS1005953019 (12:55971900 T>A,C), RS1006252778 (12:55968708 A>G,T), RS1006815089 (12:55971592 T>C,G), RS1006866115 (12:55969972 C>G), RS1006897027 (12:55969584 GGCTT>G), RS1007192310 (12:55970791 T>A), RS1008008049 (12:55966885 G>A,C,T)

Disease associations

OMIM: gene MIM:116953 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000141_1	Type 1 diabetes	9.000000e-10
GCST001183_11	Asthma	1.000000e-10
GCST001670_1	Vitiligo	8.000000e-12
GCST002318_131	Rheumatoid arthritis	1.000000e-10
GCST002318_5	Rheumatoid arthritis	2.000000e-08
GCST004367_1	Anorexia nervosa	4.000000e-09
GCST006959_166	Rheumatoid arthritis	1.000000e-09
GCST006959_35	Rheumatoid arthritis	9.000000e-08
GCST007563_23	Allergic disease (asthma, hay fever or eczema)	4.000000e-10
GCST007564_9	Asthma or allergic disease (pleiotropy)	1.000000e-13
GCST007993_28	Asthma (adult onset)	6.000000e-07
GCST007995_39	Asthma (childhood onset)	1.000000e-11
GCST008832_15	Gastroesophageal reflux disease	1.000000e-08
GCST008916_124	Asthma	1.000000e-16
GCST010002_217	Refractive error	6.000000e-174
GCST010703_297	Brain morphology (MOSTest)	4.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:1002011	adult onset asthma
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (21): CHEMBL1907605 (PROTEIN COMPLEX), CHEMBL2094126 (PROTEIN COMPLEX), CHEMBL2094128 (PROTEIN COMPLEX), CHEMBL2111326 (SELECTIVITY GROUP), CHEMBL301 (SINGLE PROTEIN), CHEMBL3038469 (PROTEIN COMPLEX), CHEMBL3038470 (PROTEIN COMPLEX), CHEMBL3038517 (PROTEIN FAMILY), CHEMBL3559691 (PROTEIN FAMILY), CHEMBL3885552 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

85 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 383,562 (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
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL3894860	TRILACICLIB	4	2,086
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL3545110	RIBOCICLIB	4	8,018
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL554	LAPATINIB	4	69,326
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL599552	INDIGO	3	6,024
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL407874	6-O-BENZYLGUANINE	3	6,988
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL217092	SARACATINIB	3
CHEMBL300138	ENZASTAURIN	3
CHEMBL3904602	LEROCICLIB	3
CHEMBL50	QUERCETIN	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230165	SILMITASERTIB	2
CHEMBL1276127	INDIRUBIN	2
CHEMBL14762	SELICICLIB	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL3115681	NARAZACICLIB	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CDK1 subfamily

Most potent curated ligand interactions (56 total), top 25:

Ligand	Action	Affinity	Parameter
PF-06873600	Inhibition	9.92	pKi
compound 17 [PMID: 38325398]	Inhibition	9.54	pIC50
QR-6401	Inhibition	9.43	pIC50
Cdk1/2 inhibitor III	Inhibition	9.3	pIC50
aloisine	Inhibition	9.28	pKi
tanuxiciclib	Inhibition	9.05	pIC50
compound 9b [PMID: 18986805]	Inhibition	9.0	pIC50
tagtociclib	Inhibition	8.94	pIC50
JNJ-7706621	Inhibition	8.7	pIC50
dinaciclib	Inhibition	8.7	pIC50
culmerciclib	Inhibition	8.62	pIC50
compound 5g [PMID: 36385925]	Inhibition	8.59	pIC50
asnuciclib	Inhibition	8.52	pKi
R547	Inhibition	8.52	pKi
RGB-286638	Inhibition	8.52	pIC50
BS-194	Inhibition	8.52	pIC50
compound 3 [PMID: 19097791]	Inhibition	8.39	pIC50
zotiraciclib	Inhibition	8.3	pIC50
CDK inhibitor 4.35	Inhibition	8.22	pIC50
purvalanol B	Inhibition	8.22	pIC50
AZD5438	Inhibition	8.22	pIC50
roniciclib	Inhibition	8.05	pIC50
BMS-265246	Inhibition	8.05	pIC50
vustanaciclib	Inhibition	8.0	pIC50
SU9516	Inhibition	7.57	pIC50

Binding affinities (BindingDB)

2188 measured of 2972 human assays (3139 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-({6-(2-hydroxyethyl)-8-[(1R,2S)-2-methylcyclopentyl]-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl}amino)-N-methylpiperidine-1-sulfonamide	KI	0.06 nM	US-10233188: CDK2/4/6 inhibitors
6-methyl-8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.06 nM	US-10233188: CDK2/4/6 inhibitors
6-(2-hydroxyethyl)-8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.08 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(1-methylimidazol-4-yl)sulfonylpiperidin-4-yl]amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.08 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.08 nM	US-10233188: CDK2/4/6 inhibitors
US10233188, Example 187	KI	0.08 nM	US-10233188: CDK2/4/6 inhibitors
4-[[6-(2,2-difluoroethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.09 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.09 nM	US-10233188: CDK2/4/6 inhibitors
N-methyl-4-[[8-[(1R,2S)-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]piperidine-1-sulfonamide	KI	0.09 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.09 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(1-methylpyrazol-4-yl)sulfonylpiperidin-4-yl]amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.1 nM	US-10233188: CDK2/4/6 inhibitors
2-[(1-ethylsulfonylpiperidin-4-yl)amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methylpyrido[2,3-d]pyrimidin-7-one	KI	0.1 nM	US-10233188: CDK2/4/6 inhibitors
BDBM467191	KI	0.1 nM	US-10233188: CDK2/4/6 inhibitors
6-(2-hydroxyethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.11 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(2-methoxyethylsulfonyl)piperidin-4-yl]amino]-8-[(1R,2S)-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.12 nM	US-10233188: CDK2/4/6 inhibitors
2-[(1-cyclopropylsulfonylpiperidin-4-yl)amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methylpyrido[2,3-d]pyrimidin-7-one	KI	0.12 nM	US-10233188: CDK2/4/6 inhibitors
4-[[6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]piperidine-1-sulfonamide	KI	0.12 nM	US-10233188: CDK2/4/6 inhibitors
US10233188, Example 201	KI	0.12 nM	US-10233188: CDK2/4/6 inhibitors
US10233188, Example 221	KI	0.13 nM	US-10233188: CDK2/4/6 inhibitors
N-(2,2-difluoropropyl)-4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]piperidine-1-sulfonamide	KI	0.14 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(1,1-dioxothiolan-3-yl)sulfonylpiperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methylpyrido[2,3-d]pyrimidin-7-one	KI	0.14 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(cyclopropylmethylsulfonyl)piperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methylpyrido[2,3-d]pyrimidin-7-one	KI	0.15 nM	US-10233188: CDK2/4/6 inhibitors
6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)-piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.16 nM	US-10233188: CDK2/4/6 inhibitors
2-[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]-7-oxopyrido[2,3-d]pyrimidin-6-yl]acetonitrile	KI	0.16 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(2-methoxyethylsulfonyl)piperidin-4-yl]amino]-6-methylpyrido[2,3-d]pyrimidin-7-one	KI	0.17 nM	US-10233188: CDK2/4/6 inhibitors
4-[[6-(difluoromethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.17 nM	US-10233188: CDK2/4/6 inhibitors
4-[(8-cyclopentyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]piperidine-1-sulfonamide	KI	0.19 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.2 nM	US-10233188: CDK2/4/6 inhibitors
2-[(1-cyclopropylsulfonylpiperidin-4-yl)amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.2 nM	US-10233188: CDK2/4/6 inhibitors
4-[[6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.2 nM	US-10233188: CDK2/4/6 inhibitors
N-(2,2-difluoropropyl)-4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]piperidine-1-sulfonamide	KI	0.21 nM	US-10233188: CDK2/4/6 inhibitors
2-[(1-ethylsulfonylpiperidin-4-yl)amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.21 nM	US-10233188: CDK2/4/6 inhibitors
4-[(8-cyclopentyl-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]piperidine-1-sulfonamide	KI	0.22 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-(oxan-4-yl)piperidine-1-sulfonamide	KI	0.24 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-[[(2R)-oxolan-2-yl]methyl]piperidine-1-sulfonamide	KI	0.24 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(1,1-dioxothiolan-3-yl)sulfonylpiperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.25 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(1,3-thiazol-2-ylsulfonyl)piperidin-4-yl]amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.25 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(1,3,4-thiadiazol-2-ylsulfonyl)piperidin-4-yl]amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.25 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(cyclopropylmethylsulfonyl)piperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.25 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,3R)-3-hydroxycyclohexyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]-amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.26 nM	US-10233188: CDK2/4/6 inhibitors
6-chloro-8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.27 nM	US-10233188: CDK2/4/6 inhibitors
2-[8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]-7-oxopyrido[2,3-d]pyrimidin-6-yl]acetamide	KI	0.27 nM	US-10233188: CDK2/4/6 inhibitors
6-(hydroxymethyl)-8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.27 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(fluoromethylsulfonyl)piperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.27 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-[[(2S)-oxolan-2-yl]methyl]piperidine-1-sulfonamide	KI	0.27 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.28 nM	US-10233188: CDK2/4/6 inhibitors
4-[(8-cycloheptyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]piperidine-1-sulfonamide	KI	0.29 nM	US-10233188: CDK2/4/6 inhibitors
3-(4-sulfamoylphenyl)-3,4,10,11-tetraazatricyclo[7.3.0.0^{2,6}]dodeca-1(9),2(6),4,7,11-pentaene-5-carboxamide	IC50	0.3 nM
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-(2-methoxy-2-methylpropyl)piperidine-1-sulfonamide	KI	0.33 nM	US-10233188: CDK2/4/6 inhibitors
4-{[3-(4-nitrophenyl)-1H-pyrazol-5-yl]amino}benzene-1-sulfonamide	IC50	0.33 nM

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.40	Ki	0.04	nM	CHEMBL5899718
10.30	Ki	0.05	nM	CHEMBL5762472
10.22	Ki	0.06	nM	CHEMBL5774115
10.22	Ki	0.06	nM	CHEMBL5817327
10.22	Ki	0.06	nM	CHEMBL5857215
10.15	Ki	0.07	nM	CHEMBL5808436
10.15	Ki	0.07	nM	CHEMBL5975537
10.10	Ki	0.08	nM	CHEMBL5764489
10.10	Ki	0.08	nM	CHEMBL5877168
10.10	Ki	0.08	nM	CHEMBL5278622
10.10	Ki	0.08	nM	CHEMBL5963572
10.10	Ki	0.08	nM	CHEMBL5805501
10.10	Ki	0.08	nM	CHEMBL5876770
10.10	Ki	0.08	nM	CHEMBL5975537
10.05	Ki	0.09	nM	CHEMBL4750658
10.05	Ki	0.09	nM	EBVACICLIB
10.05	Ki	0.09	nM	CHEMBL5281770
10.05	Ki	0.09	nM	CHEMBL5746772
10.05	Ki	0.09	nM	CHEMBL5967788
10.05	Ki	0.09	nM	CHEMBL6005561
10.05	Ki	0.09	nM	CHEMBL5281860
10.05	Ki	0.09	nM	CHEMBL5765623
10.05	Ki	0.09	nM	CHEMBL5813951
10.05	Ki	0.09	nM	CHEMBL5805501
10.05	Ki	0.09	nM	CHEMBL5994701
10.00	IC50	0.1	nM	STAUROSPORINE
10.00	Ki	0.1	nM	CHEMBL4744945
10.00	Ki	0.1	nM	CHEMBL4797526
10.00	Ki	0.1	nM	CHEMBL5950749
10.00	Ki	0.1	nM	CHEMBL6042439
10.00	Ki	0.1	nM	CHEMBL6047683
10.00	Ki	0.1	nM	CHEMBL5804029
10.00	Ki	0.1	nM	CHEMBL5776785
10.00	Ki	0.1	nM	CHEMBL5909080
10.00	Ki	0.1	nM	CHEMBL5883663
10.00	Ki	0.1	nM	CHEMBL5893129
9.96	Ki	0.11	nM	CHEMBL5281860
9.96	Ki	0.11	nM	CHEMBL5964436
9.96	Ki	0.11	nM	CHEMBL5921041
9.96	Ki	0.11	nM	CHEMBL5828800
9.96	Ki	0.11	nM	CHEMBL5886881
9.96	Ki	0.11	nM	CHEMBL6022715
9.96	Ki	0.11	nM	CHEMBL5948920
9.92	Ki	0.12	nM	CHEMBL4764153
9.92	Ki	0.12	nM	CHEMBL4748471
9.92	Ki	0.12	nM	EBVACICLIB
9.92	Ki	0.12	nM	CHEMBL5278622
9.92	Ki	0.12	nM	CHEMBL5847372
9.92	Ki	0.12	nM	CHEMBL5900389
9.92	Ki	0.12	nM	CHEMBL5816880

PubChem BioAssay actives

2952 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
4-[[4-(3,4-dimethyl-2-oxo-1,3-thiazol-5-yl)pyrimidin-2-yl]amino]-N-(2-methoxyethyl)benzenesulfonamide	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	0.0001	uM
6-(2,2-difluoroethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933531: Inhibition of CDK2/cyclin E1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0001	uM
6-(difluoromethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
6-(2,2-difluoroethyl)-8-[(1S,2S)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933531: Inhibition of CDK2/cyclin E1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0001	uM
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933531: Inhibition of CDK2/cyclin E1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0001	uM
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]piperidine-1-sulfonamide	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
8-[(1R,2S,3R)-3-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
[(1S,3R)-3-[3-[[2-(6-methoxy-3-pyridinyl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] 2,2-dimethylazetidine-1-carboxylate	1678540: Inhibition of recombinant full length wild-type CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
[(1R,3S)-3-[3-[[2-(6-methoxy-3-pyridinyl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] 2,2-dimethylazetidine-1-carboxylate	1678540: Inhibition of recombinant full length wild-type CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
[(1R,3S)-3-[3-[[2-(2-methyl-1,3-thiazol-5-yl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] (2S,3R)-3-cyano-2-methylazetidine-1-carboxylate	1678540: Inhibition of recombinant full length wild-type CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
[(2S)-2-methylazetidin-1-yl]-[2-[(1-methylsulfonylpiperidin-4-yl)amino]quinazolin-7-yl]methanone	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0001	uM
6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933531: Inhibition of CDK2/cyclin E1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0002	uM
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0002	uM
4-[[6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0002	uM
2-[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]-7-oxopyrido[2,3-d]pyrimidin-6-yl]acetonitrile	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0002	uM
[(1R,3S)-3-[3-[[2-(6-methoxy-3-pyridinyl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] (2S,3R)-3-cyano-2-methylazetidine-1-carboxylate	1678540: Inhibition of recombinant full length wild-type CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0002	uM
3-fluoro-4-[[7-[(2S,3R)-3-methoxy-2-methylazetidine-1-carbonyl]pyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylbenzenesulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0002	uM
N,3-dimethyl-4-[[7-[(2S)-2-methylpyrrolidine-1-carbonyl]quinazolin-2-yl]amino]benzenesulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0002	uM
ethyl 2-[(2E)-2-[1-(6-chloro-2-oxo-3,4-dihydrochromen-3-yl)ethylidene]hydrazinyl]-4-methyl-1,3-thiazole-5-carboxylate	1927555: Inhibition of CDK2/cyclin E1 (unknown origin) incubated for 60 mins in presence of ATP by ADP-Glo luminescent Kinase Assay	ic50	0.0002	uM
ethyl 2-[(2E)-2-[1-(6-bromo-2-oxo-3,4-dihydrochromen-3-yl)ethylidene]hydrazinyl]-4-methyl-1,3-thiazole-5-carboxylate	1927555: Inhibition of CDK2/cyclin E1 (unknown origin) incubated for 60 mins in presence of ATP by ADP-Glo luminescent Kinase Assay	ic50	0.0002	uM
4-[[7-[(2S)-2-methylpyrrolidine-1-carbonyl]quinazolin-2-yl]amino]piperidine-1-sulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0002	uM
3-fluoro-4-[[7-[(2S,3R)-3-fluoro-2-methylazetidine-1-carbonyl]pyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylbenzenesulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0002	uM
3-fluoro-N-methyl-4-[[7-[(2S)-2-methylazetidine-1-carbonyl]pyrido[2,3-d]pyrimidin-2-yl]amino]benzenesulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0002	uM
[(2R)-2-methylpyrrolidin-1-yl]-[2-[(1-methylsulfonylpiperidin-4-yl)amino]quinazolin-7-yl]methanone	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0002	uM
N-(3-nitrophenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine	348897: Inhibition of human CDK2 by HTRF assay	ic50	0.0003	uM
4-[(8-cycloheptyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]piperidine-1-sulfonamide	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0003	uM
2-[[1-(cyclopropylmethylsulfonyl)piperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0003	uM
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0003	uM
4-[[7’-[(1R,3R)-3-hydroxycyclohexyl]-6’-oxospiro[cyclopropane-1,5’-pyrrolo[2,3-d]pyrimidine]-2’-yl]amino]-N-methylbenzenesulfonamide	1875689: Inhibition of recombinant human N-terminal GST-tagged full-length CDK2/Flag-tagged cyclinE1 expressed in baculovirus expression system using eIF4E-binding protein-1 peptide as substrate incubated for 1 hr in presence of ATP by HTRF assay	ic50	0.0003	uM
N-methyl-4-[[7’-[(1S,2S)-2-methylcyclopentyl]-6’-oxospiro[cyclopropane-1,5’-pyrrolo[2,3-d]pyrimidine]-2’-yl]amino]benzenesulfonamide	1875689: Inhibition of recombinant human N-terminal GST-tagged full-length CDK2/Flag-tagged cyclinE1 expressed in baculovirus expression system using eIF4E-binding protein-1 peptide as substrate incubated for 1 hr in presence of ATP by HTRF assay	ic50	0.0003	uM
N-[1-(1-methylimidazol-4-yl)sulfonylpiperidin-4-yl]-4-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-5-(trifluoromethyl)pyrimidin-2-amine	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0003	uM
2-[(1-pyridin-2-ylsulfonylpiperidin-4-yl)amino]-4-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]pyrimidine-5-carbonitrile	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0003	uM
1-[4-[2-[(1-cyclopropylsulfonylpiperidin-4-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]pyrazol-1-yl]-2-methylpropan-2-ol	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0003	uM
2-[[1-(1-methylimidazol-4-yl)sulfonylpiperidin-4-yl]amino]-4-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]pyrimidine-5-carbonitrile	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0003	uM
3-chloro-4-[4-[2-[(1-methylsulfonylpiperidin-4-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]pyrazol-1-yl]benzonitrile	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0003	uM
4-[[7’-[(1R,2R)-2-methylcyclopentyl]-6’-oxospiro[cyclopropane-1,5’-pyrrolo[2,3-d]pyrimidine]-2’-yl]amino]-N-[(3R)-1-methylpiperidin-3-yl]benzenesulfonamide	1875689: Inhibition of recombinant human N-terminal GST-tagged full-length CDK2/Flag-tagged cyclinE1 expressed in baculovirus expression system using eIF4E-binding protein-1 peptide as substrate incubated for 1 hr in presence of ATP by HTRF assay	ic50	0.0003	uM
N-methyl-4-[[7-[(2S)-2-methylpyrrolidine-1-carbonyl]quinazolin-2-yl]amino]benzenesulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0003	uM
8-cycloheptyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933531: Inhibition of CDK2/cyclin E1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0004	uM
4-[1-[2-chloro-4-(methylaminomethyl)phenyl]pyrazol-4-yl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0004	uM
2-methyl-1-[4-[2-[(1-methylsulfonylpiperidin-4-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]pyrazol-1-yl]propan-2-ol	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0004	uM
N-[1-(1-methylpyrazol-4-yl)sulfonylpiperidin-4-yl]-4-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-5-(trifluoromethyl)pyrimidin-2-amine	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0004	uM
4-[[7-[(2S,3R)-3-cyano-2-methylazetidine-1-carbonyl]pyrido[2,3-d]pyrimidin-2-yl]amino]-3-fluoro-N-methylbenzenesulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0004	uM
3-[[4-(3,4-dimethyl-2-oxo-1,3-thiazol-5-yl)pyrimidin-2-yl]amino]benzonitrile	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	0.0005	uM
N-[2-(2-hydroxyethoxy)ethyl]-4-[(7-hydroxy-6H-pyrrolo[2,3-g][1,3]benzothiazol-8-yl)methylideneamino]benzenesulfonamide	53362: Inhibitory activity against human cyclin-dependent kinase 2 (CDK2)	ic50	0.0005	uM
[(1S,3R)-3-[3-[[2-(6-methoxy-3-pyridinyl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] N-(4-hydroxycyclohexyl)carbamate	1678540: Inhibition of recombinant full length wild-type CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0005	uM
4-[1-[2-chloro-4-(methylaminomethyl)phenyl]pyrazol-4-yl]-N-(1-methylsulfonylpiperidin-4-yl)-5-(trifluoromethyl)pyrimidin-2-amine	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0005	uM
4-[[7-[(2S,4S)-4-fluoro-2-methylpyrrolidine-1-carbonyl]quinazolin-2-yl]amino]-N,3-dimethylbenzenesulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0005	uM
8-cyclopentyl-6-methyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933531: Inhibition of CDK2/cyclin E1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0006	uM
4-[[7’-(2-chloro-5-fluorophenyl)-6’-oxospiro[cyclopropane-1,5’-pyrrolo[2,3-d]pyrimidine]-2’-yl]amino]-N-methylbenzenesulfonamide	1875689: Inhibition of recombinant human N-terminal GST-tagged full-length CDK2/Flag-tagged cyclinE1 expressed in baculovirus expression system using eIF4E-binding protein-1 peptide as substrate incubated for 1 hr in presence of ATP by HTRF assay	ic50	0.0006	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases activity, decreases phosphorylation, decreases reaction (+5 more)	9
Estradiol	decreases expression, affects binding, decreases phosphorylation, increases expression, increases phosphorylation (+4 more)	9
Troglitazone	affects response to substance, decreases expression, decreases activity, increases response to substance, increases reaction (+2 more)	8
Quercetin	decreases activity, decreases expression, affects cotreatment, affects binding, increases expression (+3 more)	8
Resveratrol	increases reaction, decreases activity, decreases expression, decreases reaction, affects binding (+3 more)	7
Cisplatin	affects reaction, increases reaction, affects binding, decreases activity, decreases reaction (+5 more)	7
Tretinoin	affects cotreatment, decreases reaction, decreases degradation, affects binding, decreases expression (+3 more)	7
bisphenol A	affects expression, affects cotreatment, decreases expression, decreases phosphorylation, increases expression (+1 more)	6
Benzo(a)pyrene	increases expression, affects methylation, decreases expression	6
alvocidib	decreases expression, affects binding, decreases activity, decreases reaction, increases activity	5
palbociclib	decreases activity, decreases expression, decreases phosphorylation, increases expression, increases phosphorylation	5
indole-3-carbinol	decreases activity, increases reaction, decreases expression, affects localization, affects binding	4
Arsenic Trioxide	affects binding, increases reaction, decreases activity, decreases expression, affects cotreatment (+2 more)	4
Cannabidiol	decreases expression, affects cotreatment	4
Doxorubicin	decreases reaction, affects response to substance, increases response to substance, affects activity, affects cotreatment (+2 more)	4
Fluorouracil	affects response to substance, increases expression, affects cotreatment	4
Plant Extracts	decreases activity, decreases expression, increases expression	4
Tamoxifen	affects binding, affects cotreatment, increases reaction, decreases activity, decreases expression (+1 more)	4
Sirolimus	decreases phosphorylation, affects cotreatment, affects localization, affects binding, increases reaction (+2 more)	4
geraniol	affects binding, decreases activity, increases reaction, decreases expression	3
methylselenic acid	affects reaction, decreases expression, affects binding, increases reaction, decreases activity	3
U 0126	decreases expression, decreases reaction, decreases phosphorylation	3
Fulvestrant	increases expression, affects cotreatment, increases methylation, decreases reaction, increases activity (+1 more)	3
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	3
DDT	increases activity, increases phosphorylation, decreases reaction	3
Dexamethasone	decreases expression, decreases reaction, affects binding, decreases activity, increases expression	3
Drugs, Chinese Herbal	increases expression, increases reaction, decreases expression	3
Etoposide	decreases reaction, increases expression, affects reaction, increases phosphorylation, affects response to substance	3
Indomethacin	decreases activity, increases reaction, decreases expression	3
Ouabain	decreases expression	3

ChEMBL screening assays

2469 unique, capped per target: 2394 binding, 59 functional, 14 admet, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1047830	Binding	Residual activity of CDK2/Cyclin E at 10 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem
CHEMBL4325185	ADMET	Inhibition of human CDK2/Cylcin E at 1 uM relative to control	Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5-b]pyridazines for the Treatment of Human African Trypanosomiasis. — J Med Chem
CHEMBL5229241	Toxicity	Inhibition of human Cdk2/Cyclin A using Myelin basic protein as substrate by ATP competitive assay	Engineering Selectivity for Reduced Toxicity of Bacterial Kinase Inhibitors Using Structure-Guided Medicinal Chemistry. — ACS Med Chem Lett

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8TV	Abcam MCF-7 CDK2 KO	Cancer cell line	Female
CVCL_D8IR	Ubigene HCT 116 CDK2 KO	Cancer cell line	Male
CVCL_D9BN	Ubigene HEK293 CDK2 KO	Transformed cell line	Female
CVCL_D9ZU	Ubigene HeLa CDK2 KO	Cancer cell line	Female
CVCL_HD72	HCT 116 CDK2(-/-)	Cancer cell line	Male
CVCL_KT47	HeLa SilenciX CDK2	Cancer cell line	Female
CVCL_LD87	HCT 116 CDK2 (D145N/+)	Cancer cell line	Male
CVCL_SI32	HAP1 CDK2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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