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
• Regional missense constraint (gnomAD): 3 of 5 regions constrained (≈45% of expected missense variation)
• GTEx eGene: eQTL in 9 tissues, sQTL in 3 (q < 0.05)
• Drug target: yes — 11 curated mechanism-of-action drugs; 85 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Cancer dependency (DepMap): dependent in 71.1% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.39 (moderately constrained)
• MANE Select transcript: NM_001798
• Interaction hub: 4,908 STRING partners (top 1% of genes corpus-wide)

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: 13 — 5 protein_coding, 5 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000266970

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 3: 4, TSL 5: 4

ENST00000266970, ENST00000354056, ENST00000440311, ENST00000553376, ENST00000554545, ENST00000554619, ENST00000555357, ENST00000555408, ENST00000556146, ENST00000556276, ENST00000556464, ENST00000556656, ENST00001135426

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
ENSE00002260310	55966830	55967124
ENSE00003566576	55971044	55971247
ENSE00003600826	55968778	55968948
ENSE00003639718	55969475	55969576
ENSE00003656909	55967857	55967934
ENSE00003659990	55968049	55968169
ENSE00004786701	55971521	55972789

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.

Highest expression (Bgee): ventricular zone, ganglionic eminence, embryo, lower esophagus muscularis layer, lower esophagus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CDK2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 9 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

12 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Muscularis	eqtl	6.4e-07	-0.20	12:55972376:G:C
Muscle Skeletal	eqtl	4.8e-04	-0.23	12:55971915:C:A
Small Intestine Terminal Ileum	eqtl	6.7e-04	-1.85	12:55739898:G:A
Cells Cultured fibroblasts	eqtl	1.2e-03	+0.11	12:55969882:C:A
Esophagus Gastroesophageal Junction	eqtl	2.5e-03	-0.36	12:55975440:G:A
Whole Blood	sqtl	5.7e-03	-1.05	12:56235762:A:G
Artery Tibial	sqtl	9.7e-03	+0.89	12:55813418:C:T
Pituitary	sqtl	9.8e-03	+1.08	12:56160200:CACTT:C
Cells EBV-transformed lymphocytes	eqtl	1.3e-02	+0.68	12:56700138:C:T
Adipose Visceral Omentum	eqtl	1.5e-02	-0.19	12:56152939:C:T
Whole Blood	eqtl	3.3e-02	+0.07	12:55700033:T:G
Colon Transverse	eqtl	3.8e-02	-0.12	12:55936788:G:A

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

showing 100 of 287 tissues 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
ovary	UBERON:0000992	87.74	gold quality
thoracic aorta	UBERON:0001515	87.59	gold quality
ascending aorta	UBERON:0001496	87.57	gold quality
islet of Langerhans	UBERON:0000006	87.48	gold quality
esophagus mucosa	UBERON:0002469	87.27	gold quality
adipose tissue of abdominal region	UBERON:0007808	87.05	gold quality
aorta	UBERON:0000947	86.96	gold quality
mucosa of transverse colon	UBERON:0004991	86.95	gold quality
lower esophagus mucosa	UBERON:0035834	86.89	gold quality
bone marrow cell	CL:0002092	86.87	gold quality
body of stomach	UBERON:0001161	86.85	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.73	gold quality
tibial artery	UBERON:0007610	86.70	gold quality
popliteal artery	UBERON:0002250	86.68	gold quality
endometrium epithelium	UBERON:0004811	86.61	gold quality
lymph node	UBERON:0000029	86.59	gold quality
minor salivary gland	UBERON:0001830	86.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.17	gold quality
right coronary artery	UBERON:0001625	86.07	gold quality
bone marrow	UBERON:0002371	86.06	gold quality
spleen	UBERON:0002106	85.93	gold quality
transverse colon	UBERON:0001157	85.70	gold quality
hair follicle	UBERON:0002073	85.69	silver quality
pancreas	UBERON:0001264	85.61	gold quality
smooth muscle tissue	UBERON:0001135	85.53	gold quality
vagina	UBERON:0000996	85.46	gold quality
granulocyte	CL:0000094	85.43	gold quality
left coronary artery	UBERON:0001626	85.31	gold quality
stomach	UBERON:0000945	85.26	gold quality
body of pancreas	UBERON:0001150	85.16	gold quality
small intestine	UBERON:0002108	85.04	gold quality
left lobe of thyroid gland	UBERON:0001120	84.86	gold quality
tonsil	UBERON:0002372	84.83	gold quality
sigmoid colon	UBERON:0001159	84.80	gold quality
thymus	UBERON:0002370	84.72	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.71	gold quality
right lobe of liver	UBERON:0001114	84.68	gold quality
mouth mucosa	UBERON:0003729	84.67	gold quality
seminal vesicle	UBERON:0000998	84.61	gold quality
caecum	UBERON:0001153	84.44	gold quality
right atrium auricular region	UBERON:0006631	84.44	gold quality
female reproductive system	UBERON:0000474	84.42	gold quality
metanephros cortex	UBERON:0010533	84.33	gold quality
intestine	UBERON:0000160	84.32	gold quality
colon	UBERON:0001155	84.31	gold quality
right lobe of thyroid gland	UBERON:0001119	84.25	gold quality
lung	UBERON:0002048	84.14	gold quality
coronary artery	UBERON:0001621	84.01	gold quality
large intestine	UBERON:0000059	83.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.90	gold quality
right adrenal gland	UBERON:0001233	83.83	gold quality
thyroid gland	UBERON:0002046	83.78	gold quality
left adrenal gland	UBERON:0001234	83.75	gold quality
left adrenal gland cortex	UBERON:0035825	83.60	gold quality
nerve	UBERON:0001021	83.42	gold quality
tibial nerve	UBERON:0001323	83.42	gold quality
cardiac atrium	UBERON:0002081	83.27	gold quality
prostate gland	UBERON:0002367	83.00	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.97	gold quality
upper leg skin	UBERON:0004262	82.86	gold quality
right adrenal gland cortex	UBERON:0035827	82.86	gold quality
urinary bladder	UBERON:0001255	82.74	gold quality
adrenal gland	UBERON:0002369	82.73	gold quality
right uterine tube	UBERON:0001302	82.53	gold quality
saliva-secreting gland	UBERON:0001044	82.39	gold quality
uterus	UBERON:0000995	82.34	gold quality
adipose tissue	UBERON:0001013	82.11	gold quality
apex of heart	UBERON:0002098	82.09	gold quality
connective tissue	UBERON:0002384	81.91	gold quality
heart left ventricle	UBERON:0002084	81.90	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Placenta	tissue	44.4	medium
Thymus	tissue	34.7
Bone marrow	tissue	33.9	medium
Tonsil	tissue	23.2	medium
Skin 1	tissue	21.5	low
Lymph node	tissue	20.1	medium
Smooth muscle	tissue	18.2	not detected
Urinary bladder	tissue	16.9	low
Ovary	tissue	16.6	not detected
Appendix	tissue	15.4	medium
Liver	tissue	15.1	not detected
Rectum	tissue	14.0	medium
Seminal vesicle	tissue	13.5	not detected
Endometrium 1	tissue	12.8	not detected
Vagina	tissue	12.7	low
Colon	tissue	10.8	low
Lung	tissue	10.6	not detected
Breast	tissue	10.5	not detected
Gallbladder	tissue	10.2	low
Spleen	tissue	9.8	not detected
Prostate	tissue	9.5	low
Small intestine	tissue	9.3	medium
Esophagus	tissue	9.2	medium
Duodenum	tissue	9.2	medium
Fallopian tube	tissue	8.9	low
Stomach 1	tissue	8.8	not detected
Adipose tissue	tissue	8.8	not detected
Choroid plexus	tissue	8.2
Cervix	tissue	8.1	low
Pancreas	tissue	8.1	not detected
Salivary gland	tissue	7.8	not detected
Tongue	tissue	7.6
Parathyroid gland	tissue	7.4	not detected
Kidney	tissue	6.9	low
Thyroid gland	tissue	6.7	low
Adrenal gland	tissue	6.6	low
Heart muscle	tissue	6.3	low
Testis	tissue	6.1	medium
Retina	tissue	6.0
Epididymis	tissue	5.9	low
Pituitary gland	tissue	4.8
Skeletal muscle	tissue	4.6	not detected
Spinal cord	tissue	2.9
Hippocampus	tissue	2.5	low
Superior colliculi	tissue	2.4
Substantia nigra	tissue	2.2
Postcentral gyrus	tissue	2.2
Pons	tissue	2.1
Medulla oblongata	tissue	2.0
Locus coeruleus	tissue	2.0
Periaqueductal gray	tissue	2.0
Thalamus	tissue	1.9
Hypothalamus	tissue	1.9
Midbrain	tissue	1.8
Corpus callosum	tissue	1.8
Basal ganglia	tissue	1.7	low
Nucleus accumbens	tissue	1.7
Hippocampal formation	tissue	1.7
Caudate putamen	tissue	1.7
Cerebral cortex	tissue	1.6	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Blood vessel (13.1), Area postrema (4.9), Cervical spinal cord, ventral horn (4.0), Anterior thalamic nucleus, ventral (3.9), Dorsal cochlear nucleus (3.8).

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)

Targeting CDK2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 76 miRNAs:

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

gnomAD constraint: pLI 0.999, LOEUF 0.39, missense Z 2.93 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000266970 splits into 5 regions with different missense tolerance; 3 are missense-constrained (≈45% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
12:55,967,009–55,968,131	37 / 108.4	0.34	yes (p 7.0e-12)
12:55,968,132–55,968,888	47 / 59.5	0.79	no
12:55,968,889–55,968,932	6 / 18.4	0.33	yes (p 3.8e-03)
12:55,968,933–55,969,559	5 / 39.5	0.13	yes (p 4.1e-08)
12:55,969,560–55,971,622	106 / 141.3	0.75	no
DepMap (CRISPR cell-line fitness): dependent in 71.1% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): KLE (-2.998), KURAMOCHI (-2.551), NIH:OVCAR-3 (-2.433), MFE-280 (-2.348), SNU-1077 (-2.247), SNB75 (-2.191), EFO-21 (-2.021), HCC1937 (-1.915), SNU-182 (-1.895), ONCO-DG-1 (-1.847), COV318 (-1.795), AM-38 (-1.751), NCI-H1694 (-1.733), GCIY (-1.727), U-87 MG (-1.686).

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:104772) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 33 distinct phenotype terms.

Mouse phenotype (MP)	Records
small testis	2
infertility	2
testicular atrophy	2
ovary atrophy	2
azoospermia	2
abnormal male meiosis	2
abnormal female reproductive system morphology	1
abnormal oocyte morphology	1
abnormal ovary morphology	1
absent corpus luteum	1
abnormal male reproductive system morphology	1
small seminiferous tubules	1
abnormal spermatogenesis	1
decreased body weight	1
decreased body size	1
reduced male fertility	1
male infertility	1
female infertility	1
abnormal gametogenesis	1
abnormal meiosis	1
abnormal oogenesis	1
abnormal spermiogenesis	1
abnormal fertility/fecundity	1
abnormal seminiferous tubule morphology	1
absent ovarian follicles	1

+8 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Oryza sativa Indica Group	A2XUW1	100.0%	Diamond
Ovis aries	B2MVY4	100.0%	Diamond
Cryptococcus deneoformans JEC21	P0CS76	100.0%	Diamond
Cryptococcus deneoformans B-3501A	P0CS77	100.0%	Diamond
Plasmodium falciparum 3D7	P61075	100.0%	Diamond
Bos taurus	Q02399	100.0%	Diamond
Plasmodium falciparum K1	Q07785	100.0%	Diamond
Callithrix jacchus	B0VXE8	99.8%	Diamond
Oryza sativa Japonica Group	P29620	99.8%	Diamond
Pyricularia oryzae 70-15	G4NH08	99.7%	Diamond
Cricetulus griseus	O55076	99.7%	Diamond
Mesocricetus auratus	P48963	99.7%	Diamond
Pyricularia oryzae	Q3S406	99.7%	Diamond
Aspergillus fischeri NRRL 181	A1D624	99.5%	Diamond
Plecturocebus moloch	B0VXL7	99.5%	Diamond
Dasypus novemcinctus	C0RW22	99.3%	Diamond
Sus scrofa	P79432	99.0%	Diamond
Oryctolagus cuniculus	B6A7Q3	98.8%	Diamond
Theileria annulata	Q26671	98.7%	Diamond
Theileria parva	Q27032	98.7%	Diamond
Vigna unguiculata	P52389	98.6%	Diamond
Lathyrus oleraceus	P19026	98.0%	Diamond
Plasmodium knowlesi strain H	O96821	97.6%	Diamond
Medicago sativa	P24923	97.3%	Diamond
Xenopus laevis	P51166	97.3%	Diamond
Petunia x hybrida	P43290	96.7%	Diamond
Xenopus tropicalis	Q0IJ08	96.5%	Diamond
Caenorhabditis briggsae	A8X5H5	95.9%	Diamond
Aspergillus clavatus NRRL 1	A1CL96	95.5%	Diamond
Aspergillus niger CBS 513.88	A2QU77	94.4%	Diamond
Aspergillus terreus NIH2624	Q0CQK1	94.4%	Diamond
Aspergillus oryzae RIB40	Q2UC58	94.4%	Diamond
Drosophila melanogaster	P48609	94.1%	Diamond
Glossina morsitans morsitans	Q2PQN9	94.1%	Diamond
Zea mays	P23111	93.9%	Diamond
Gallus gallus	P13863	93.1%	Diamond
Arabidopsis thaliana	Q08466	92.8%	Diamond
Ailuropoda melanoleuca	D2H526	92.5%	Diamond
Oxybasis rubra	P93101	92.2%	Diamond
Antirrhinum majus	Q38772	92.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
RAB5B	protein-coding	5869
IKZF4	protein-coding	64375
PMEL	protein-coding	6490
SUOX	protein-coding	6821
RPS26	protein-coding	6231
DGKA	protein-coding	1606
PYM1	protein-coding	84305

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, G3V317, G3V5T9, P24941

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). Activated by the CDK-activating kinase (CAK) complex consisting of CDK7, cyclin-H/CCNH and MAT1, which is a master regulator of CDK activity. 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. Phosphorylated and activated by CDK7 in the CDK-activating kinase (CAK) complex, and reciprocally phosphorylating its activating kinase CDK7. 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)

• 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 (94 total): helix 24, binding site 21, strand 15, mutagenesis site 8, modified residue 6, turn 5, sequence variant 4, sequence conflict 4, site 3, chain 1, domain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

showing 30 of 523 structures by resolution:

PDB	Title	Method	Resolution (Å)
6Q4G	CDK2 in complex with FragLite37	X-RAY DIFFRACTION	0.98
6Q49	CDK2 in complex with FragLite6	X-RAY DIFFRACTION	1
6Q4H	CDK2 in complex with FragLite36	X-RAY DIFFRACTION	1
6Q48	CDK2 in complex with FragLite7	X-RAY DIFFRACTION	1.03
6Q4J	CDK2 in complex with FragLite34	X-RAY DIFFRACTION	1.05
6Q4E	CDK2 in complex with FragLite33	X-RAY DIFFRACTION	1.06
6Q4K	CDK2 in complex with FragLite38	X-RAY DIFFRACTION	1.06
6Q4D	CDK2 in complex with FragLite31	X-RAY DIFFRACTION	1.07
6Q3B	CDK2 in complex with FragLite2	X-RAY DIFFRACTION	1.11
6Q4I	CDK2 in complex with FragLite35	X-RAY DIFFRACTION	1.11
6Q4B	CDK2 in complex with FragLite13	X-RAY DIFFRACTION	1.12
6Q4A	CDK2 in complex with FragLite14	X-RAY DIFFRACTION	1.13
9GNO	Crystal structure of CDK2 bound by compound 4	X-RAY DIFFRACTION	1.16
6Q3F	CDK2 in complex with FragLite2	X-RAY DIFFRACTION	1.18
6Q4F	CDK2 in complex with FragLite32	X-RAY DIFFRACTION	1.21
4EK4	Crystal structure of the cdk2 in complex with aminopyrazole inhibitor	X-RAY DIFFRACTION	1.26
4FKL	Crystal structure of the cdk2 in complex with thiazolylpyrimidine inhibitor	X-RAY DIFFRACTION	1.26
2R3I	Crystal Structure of Cyclin-Dependent Kinase 2 with inhibitor	X-RAY DIFFRACTION	1.28
6Q3C	CDK2 in complex with FragLite1	X-RAY DIFFRACTION	1.29
1GZ8	HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR …	X-RAY DIFFRACTION	1.3
5MHQ	CCT068127 in complex with CDK2	X-RAY DIFFRACTION	1.3
6GUK	CDK2 in complex with CGP74514A	X-RAY DIFFRACTION	1.3
8ERD	Cyclin-free CDK2 in complex with Cpd17	X-RAY DIFFRACTION	1.33
4EK3	Crystal structure of apo CDK2	X-RAY DIFFRACTION	1.34
2R3Q	Crystal Structure of Cyclin-Dependent Kinase 2 with inhibitor	X-RAY DIFFRACTION	1.35
7RXO	Crystal structure of CDK2 liganded with compound WN333	X-RAY DIFFRACTION	1.38
7ZPC	CDK2 in complex 9K-DOS	X-RAY DIFFRACTION	1.4
4GCJ	CDK2 in complex with inhibitor RC-3-89	X-RAY DIFFRACTION	1.42
2R3R	Crystal Structure of Cyclin-Dependent Kinase 2 with inhibitor	X-RAY DIFFRACTION	1.47
4FKU	Crystal structure of the cdk2 in complex with oxindole inhibitor	X-RAY DIFFRACTION	1.47

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, CMGC Ser/Thr protein kinases, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; basal body; calyx; centrosome; plasma membrane

Antibody reliability (HPA): IH enhanced · IF approved

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)

Position	Role
127	proton acceptor
9	cdk7 binding
88–89	cdk7 binding
166	cdk7 binding

Ligand- & substrate-binding residues (21)

Position	Role
16	ATP
17	ATP
18	ATP
33	ADP
33	ATP
81–83	ATP
81	ADP
83	ADP
86	ATP
127	Mg(2+)
129–132	ATP
132	Mg(2+)
145	ATP
145	Mg(2+)
10	ATP
11	ATP
12	ATP
13	ATP
14	ADP
14	ATP
15	ATP

Post-translational modifications (6)

Type	Positions
N-acetylmethionine	1
N6-acetyllysine	6
Phosphothreonine	14, 160
Phosphotyrosine	15, 19

Mutagenesis-validated functional residues (8)

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.
209	impairs phosphorylation by cak.

Function

Pathways and Gene Ontology

Reactome pathways

25 curated (TAS) of 75; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 75 pathways:

ID	Pathway	Evidence
R-HSA-9661069	Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) ⚕	curated
R-HSA-176187	Activation of ATR in response to replication stress	curated
R-HSA-68962	Activation of the pre-replicative complex	curated
R-HSA-69017	CDK-mediated phosphorylation and removal of Cdc6	curated
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition	curated
R-HSA-69656	Cyclin A:Cdk2-associated events at S phase entry	curated
R-HSA-69231	Cyclin D associated events in G1	curated
R-HSA-69202	Cyclin E associated events during G1/S transition	curated
R-HSA-2559586	DNA Damage/Telomere Stress Induced Senescence	curated
R-HSA-1538133	G0 and Early G1	curated
R-HSA-68911	G2 Phase	curated
R-HSA-68949	Orc1 removal from chromatin	curated
R-HSA-8849470	PTK6 Regulates Cell Cycle	curated
R-HSA-69200	Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes	curated
R-HSA-5693607	Processing of DNA double-strand break ends	curated
R-HSA-176408	Regulation of APC/C activators between G1/S and early anaphase	curated
R-HSA-9825892	Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	curated
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation	curated
R-HSA-6804757	Regulation of TP53 Degradation	curated
R-HSA-187577	SCF(Skp2)-mediated degradation of p27/p21	curated
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)	curated
R-HSA-6804116	TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	curated
R-HSA-171319	Telomere Extension By Telomerase	curated
R-HSA-9616222	Transcriptional regulation of granulopoiesis	curated
R-HSA-69563	p53-Dependent G1 DNA Damage Response	curated
R-HSA-9659787	Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects ⚕	—
R-HSA-9687139	Aberrant regulation of mitotic cell cycle due to RB1 defects ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-9675126	Diseases of mitotic cell cycle ⚕	—
R-HSA-174143	APC/C-mediated degradation of cell cycle proteins	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69620	Cell Cycle Checkpoints	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-2559583	Cellular Senescence	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-73886	Chromosome Maintenance	—
R-HSA-5693532	DNA Double-Strand Break Repair	—
R-HSA-73894	DNA Repair	—
R-HSA-69306	DNA Replication	—
R-HSA-69002	DNA Replication Pre-Initiation	—
R-HSA-1266738	Developmental Biology	—
R-HSA-180786	Extension of Telomeres	—
R-HSA-983231	Factors involved in megakaryocyte development and platelet production	electronic
R-HSA-69236	G1 Phase	—
R-HSA-69615	G1/S DNA Damage Checkpoints	—
R-HSA-69206	G1/S Transition	—
R-HSA-69481	G2/M Checkpoints	—
R-HSA-69275	G2/M Transition	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	—
R-HSA-109582	Hemostasis	—
R-HSA-5693538	Homology Directed Repair	—
R-HSA-9856651	MITF-M-dependent gene expression	—
R-HSA-9730414	MITF-M-regulated melanocyte development	—
R-HSA-1500620	Meiosis	—
R-HSA-912446	Meiotic recombination	electronic
R-HSA-453279	Mitotic G1 phase and G1/S transition	—
R-HSA-453274	Mitotic G2-G2/M phases	—

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 (27): G1/S transition of mitotic cell cycle (GO:0000082), G2/M transition of mitotic cell cycle (GO:0000086), DNA replication (GO:0006260), DNA repair (GO:0006281), chromatin remodeling (GO:0006338), protein phosphorylation (GO:0006468), 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), peptidyl-serine phosphorylation (GO:0018105), positive regulation of heterochromatin formation (GO:0031453), mitotic G1 DNA damage checkpoint signaling (GO:0031571), telomere maintenance in response to DNA damage (GO:0043247), post-translational protein modification (GO:0043687), positive regulation of DNA replication (GO:0045740), 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), DNA damage response (GO:0006974), regulation of cell cycle (GO:0051726)

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 (20): 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), 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), ciliary basal body (GO:0036064), cyclin A1-CDK2 complex (GO:0097123), cyclin A2-CDK2 complex (GO:0097124), cyclin E1-CDK2 complex (GO:0097134), cyclin E2-CDK2 complex (GO:0097135), nuclear body (GO:0016604)

Reactome top-level categories

18 top-level categories:

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
G1 Phase	1
G2/M Transition	1
p53-Dependent G1/S DNA damage checkpoint	1

GO top-level categories

showing 60 of 80 GO namespaces:

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
DNA damage response	2
protein modification process	2
cell cycle process	2
cellular process	2
regulation of cell cycle	2
protein binding	2
sex chromosome	2
endomembrane system	2
microtubule organizing center	2
cell cycle G1/S phase transition	1
cell cycle G2/M phase transition	1
DNA biosynthetic process	1
chromatin organization	1
phosphorylation	1
centrosome duplication	1
centriole assembly	1
cell communication	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
protein phosphorylation	1
regulation of heterochromatin formation	1
heterochromatin formation	1
positive regulation of cellular component biogenesis	1
positive regulation of heterochromatin organization	1
mitotic G1 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G1/S transition checkpoint signaling	1
telomere maintenance	1
DNA replication	1
regulation of DNA replication	1
positive regulation of DNA metabolic process	1
centrosome cycle	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
metal ion binding	1
protein serine/threonine kinase activity	1
cyclin-dependent protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
cyclin binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 24 of 62 annotations. The rest are phylogenetic / computational / electronic (IEA).

24 experimentally-supported GO terms:

GO term	NS	Evidence
Ras protein signal transduction	BP	expression pattern
centriole replication	BP	mutant phenotype
negative regulation of protein localization to chromatin	BP	direct assay
peptidyl-serine phosphorylation	BP	direct assay
positive regulation of cell population proliferation	BP	direct assay
positive regulation of heterochromatin formation	BP	direct assay
post-translational protein modification	BP	direct assay
protein phosphorylation	BP	direct assay
regulation of heterochromatin organization	BP	direct assay
telomere maintenance in response to DNA damage	BP	direct assay
Cajal body	CC	direct assay
centrosome	CC	direct assay
ciliary basal body	CC	direct assay
cyclin A2-CDK2 complex	CC	direct assay
cyclin-dependent protein kinase holoenzyme complex	CC	direct assay
cytoplasm	CC	direct assay
endosome	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
cyclin binding	MF	direct assay
cyclin-dependent protein kinase activity	MF	direct assay
cyclin-dependent protein serine/threonine kinase activity	MF	direct assay
protein domain specific binding	MF	physical interaction
protein serine/threonine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 4,908 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK2	CCNA1	P78396	969
CDK2	CCNA2	P20248	964
CDK2	CCNL2	Q96S94	958
CDK2	CCNE1	P24864	938
CDK2	CDKN1A	P38936	932
CDK2	CCND1	P24385	930
CDK2	CDKN1B	P46527	906
CDK2	CCNB1	P14635	901
CDK2	CDC25A	P30304	884
CDK2	TP53	P04637	880
CDK2	CCND3	P30281	876
CDK2	PCNA	P12004	873
CDK2	CCNH	P51946	858
CDK2	CDKN2A	P42771	836
CDK2	E2F1	Q01094	836

IntAct

Human interaction partners of CDK2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 87 partners by confidence:

Partner	Interaction type	MIscore	Records
CCNA2	physical association	0.980	22
CDKN1A	physical association	0.980	20
CCNE1	phosphorylation reaction	0.970	15
CDKN1B	direct interaction	0.970	12
CKS1B	physical association	0.950	19
CCNE2	association	0.940	10
CDKN3	direct interaction	0.930	6
SKP2	association	0.900	1
CCNB1	association	0.890	1
CCND1	physical association	0.880	2
CCNB2	association	0.860	4
CCNH	physical association	0.860	2
EP300	physical association	0.780	4
CCND2	physical association	0.740	1
UHRF2	physical association	0.730	5
CDK7	phosphorylation reaction	0.710	2
MAPK15	physical association	0.710	2
GMNN	association	0.640	2
IKBKG	physical association	0.630	4
RB1	phosphorylation reaction	0.620	3
SCML2	physical association	0.610	5
LATS1	physical association	0.580	3
FGFR3	physical association	0.560	3
GRIN2C	physical association	0.560	3
GSN	physical association	0.560	3
HRAS	physical association	0.560	3
E7	physical association	0.560	2
SAMHD1	association	0.530	1
SCAPER	physical association	0.520	2
CBY2	physical association	0.490	2

BioGRID (1,640 interactions; top human partners by supporting records in a sample of 600 records): CDKN1A (Affinity Capture-MS; 25 records), CDKN1B (Reconstituted Complex; 25 records), CCNE1 (Biochemical Activity; 24 records), CCNA2 (Affinity Capture-Western; 20 records), HIST1H1A (Biochemical Activity; 11 records), RBL1 (Affinity Capture-MS; 10 records), CCND1 (Affinity Capture-MS; 9 records), CKS1B (Affinity Capture-MS; 9 records), SKP2 (Affinity Capture-MS; 9 records), CCNB1 (Affinity Capture-MS; 8 records), RBL2 (Affinity Capture-MS; 8 records), CCNE2 (Affinity Capture-MS; 7 records), CDKN3 (Affinity Capture-MS; 7 records), PCNA (Affinity Capture-MS; 7 records), CCNA1 (Co-localization; 6 records)

SIGNOR signaling

showing 38 of 200 signaling 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
CDK2	up-regulates	CCDC6	phosphorylation
CDK2	up-regulates	RRN3	phosphorylation
CDK2	unknown	PTPN2	phosphorylation
CDK2	down-regulates	SMAD3	phosphorylation
CDK2	“down-regulates activity”	SMAD3	phosphorylation
CDK2	“down-regulates quantity by destabilization”	CDX2	phosphorylation
CDK2	“up-regulates activity”	RUNX1	phosphorylation
CDK2	down-regulates	WEE1	phosphorylation
CDK2	up-regulates	MCM2	phosphorylation
CDK2	up-regulates	PRKAR1A	phosphorylation
CDK2	“down-regulates quantity by destabilization”	CDKN1A	phosphorylation
CDKN1A	down-regulates	CDK2	binding
CDK2	“down-regulates activity”	RUNX1	phosphorylation
CDK2	down-regulates	FOXO1	phosphorylation
CDK2	down-regulates	LIG3	phosphorylation
CDK2	down-regulates	CDC25A	phosphorylation
CDK2	up-regulates	CDK2	phosphorylation
CDK2	down-regulates	ZC3HC1	phosphorylation
CDK2	down-regulates	CDKN1B	phosphorylation
CDKN1B	down-regulates	CDK2	binding
CDK2	up-regulates	CEBPB	phosphorylation
CDK2	up-regulates	ATRIP	phosphorylation
CDK2	unknown	ATRIP	phosphorylation
CDK2	down-regulates	HMGA1	phosphorylation
CDK2	down-regulates	ZBTB16	phosphorylation

Protein complexes (CORUM) (9)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

9 complexes by size:

Complex	Subunits	Members
★ RC complex, S-phase-specific	23	POLD4, POLE2, POLE4, CCNA2, CDK2, POLD2, POLD3, RFC2, POLE, RFC1, RFC5, RPA3, LIG1, PARP1, POLA1, POLD1, RFC3, RPA2, POLA2, POLE3, RFC4, RPA1, TOP1
★ RC sub-complex	9	RFC1, RFC3, CCNA2, POLA1, RFC2, RFC4, RFC5, CDK2, POLA2
p27-cyclinE-Cdk2 - Ubiquitin E3 ligase (SKP1A, SKP2, CUL1, CKS1B, RBX1) complex	8	CDKN1B, CKS1B, CUL1, RBX1, SKP1, SKP2, CCNE1, CDK2
Cell cycle kinase complex CDK2	4	CCND1, CDK2, CDKN1A, PCNA
E2F-1-DP-1-cyclinA-CDK2 complex	4	CCNA1, CDK2, E2F1, TFDP1
CCNE1-CDK2-CDKN1B complex	3	CDK2, CDKN1B, CCNE1
CDC25C-cyclinA-CDK2 complex	3	CCNA2, CDC25C, CDK2
CCNA2 -CDK2 complex	2	CCNA2, CDK2
CCNE1-CDK2 complex	2	CCNE1, CDK2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 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)	8	75.8×	3e-12
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	7	74.6×	1e-10
p53-Dependent G1 DNA Damage Response	6	63.9×	9e-09
p53-Dependent G1/S DNA damage checkpoint	6	63.9×	9e-09
G1/S DNA Damage Checkpoints	6	60.2×	1e-08
G1 Phase	10	58.8×	5e-14
TP53 Regulates Transcription of Cell Cycle Genes	7	56.8×	9e-10
Aberrant regulation of mitotic cell cycle due to RB1 defects	8	48.7×	1e-10

GO biological processes:

GO term	Partners	Fold	FDR
G1/S transition of mitotic cell cycle	15	36.3×	7e-17
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	5	29.9×	1e-04
positive regulation of fibroblast proliferation	6	21.4×	8e-05
G2/M transition of mitotic cell cycle	5	18.8×	7e-04
cellular senescence	5	17.8×	7e-04
Ras protein signal transduction	5	12.4×	3e-03
negative regulation of cell growth	6	10.4×	2e-03
cell division	18	10.0×	7e-11

Disease & clinical

Genetic variants

Variant evidence for CDK2: 19 ClinVar records (0 pathogenic / likely pathogenic); 16 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 397):

Position(s)	Effect	Δscore	Sites
12:55967125–55967126	donor_loss	1.0000	4
12:55967846	acceptor_gain	1.0000
12:55967855	acceptor_gain	1.0000
12:55968047–55968048	acceptor_loss	1.0000	2
12:55968170–55968171	donor_loss	1.0000	4
12:55968776–55968777	acceptor_loss	1.0000	6
12:55968949–55968950	donor_loss	1.0000	5
12:55971037	acceptor_gain	1.0000
12:55971043	acceptor_loss	1.0000
12:55967125	donor_loss	0.9900

AlphaMissense

1,274 missense substitutions predicted likely pathogenic (of 1,930 scored), across 250 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D127	8	1.000	1.000
D145	8	1.000	1.000
N132	8	0.999	1.000
D185	8	0.999	1.000
D86	8	0.998	0.999
H119	8	0.996	0.999
H125	8	0.995	0.999
D206	8	0.994	0.998
F146	8	0.992	0.999
D210	8	0.991	0.999
F203	8	0.987	0.999
F216	8	0.986	0.999
F80	8	0.983	0.997
H161	8	0.983	0.997
F240	8	0.980	0.999
H60	8	0.971	0.996
F213	8	0.961	0.999
S188	8	0.957	1.000
F152	8	0.944	0.998
S46	8	0.940	0.999

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Skin Cutaneous Melanoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

5 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	6.18e-05
Prostate Adenocarcinoma (TCGA)	unfavorable	8.81e-05
Kidney Chromophobe (TCGA)	unfavorable	0.000154
Lung Adenocarcinoma (TCGA)	unfavorable	0.000358
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000643

Disease associations

OMIM: gene MIM:116953 | disease phenotypes:

GWAS associations

16 associations:

Study	Trait	p-value
GCST010002_69	Refractive error	6e-174
GCST008916_47	Asthma	1e-16
GCST007564_22	Asthma or allergic disease (pleiotropy)	1e-13
GCST001670_1	Vitiligo	8e-12
GCST007995_39	Asthma (childhood onset)	1e-11
GCST001183_11	Asthma	1e-10
GCST002318_7	Rheumatoid arthritis	1e-10
GCST007563_24	Allergic disease (asthma, hay fever or eczema)	4e-10
GCST010703_67	Brain morphology (MOSTest)	4e-10
GCST000141_1	Type 1 diabetes	9e-10
GCST006959_66	Rheumatoid arthritis	1e-9
GCST004367_1	Anorexia nervosa	4e-9
GCST008832_14	Gastroesophageal reflux disease	1e-8
GCST002318_8	Rheumatoid arthritis	2e-8
GCST006959_137	Rheumatoid arthritis	9e-8
GCST007993_25	Asthma (adult onset)	6e-7

EFO canonical traits (from GWAS)

2 canonical traits:

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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the CDK2 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

11 curated-mechanism drugs:

Drug	Modality	Max phase
ALVOCIDIB	Small molecule	3
DINACICLIB	Small molecule	3
MILCICLIB	Small molecule	2
RG-547	Small molecule	2
SELICICLIB	Small molecule	2
UCN-01	Small molecule	2
ZOTIRACICLIB	Small molecule	2
AG-24322	Small molecule	1
BMS-387032	Small molecule	1
RGB-286638	Small molecule	1
SU-9516	Small molecule	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 389,805 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 85 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL3301610	ABEMACICLIB	4	7,497
CHEMBL2403108	CERITINIB	4	9,002
CHEMBL2028663	DABRAFENIB	4	13,060
CHEMBL553	ERLOTINIB	4	109,860
CHEMBL3301622	GILTERITINIB	4	2,542
CHEMBL554	LAPATINIB	4	70,425
CHEMBL1078178	MOMELOTINIB	4	3,649
CHEMBL502835	NINTEDANIB	4	8,978
CHEMBL2035187	PACRITINIB	4	3,544
CHEMBL189963	PALBOCICLIB	4	13,796
CHEMBL576982	QUIZARTINIB	4	4,647
CHEMBL3545110	RIBOCICLIB	4	8,501
CHEMBL1336	SORAFENIB	4	87,476
CHEMBL3894860	TRILACICLIB	4	2,213
CHEMBL428690	ALVOCIDIB	3	28,145
CHEMBL2103840	DINACICLIB	3	2,395
CHEMBL407874	6-O-BENZYLGUANINE	3	7,110
CHEMBL2105728	CRENOLANIB	3	2,278
CHEMBL3137331	DEFACTINIB	3	1,286
CHEMBL300138	ENZASTAURIN	3	3,401
CHEMBL599552	INDIGO	3
CHEMBL3904602	LEROCICLIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL50	QUERCETIN	3
CHEMBL217092	SARACATINIB	3
CHEMBL564829	MILCICLIB	2
CHEMBL384304	RG-547	2
CHEMBL14762	SELICICLIB	2
CHEMBL574737	UCN-01	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL2347597	ASNUCICLIB	2
CHEMBL445813	AT-7519	2
CHEMBL575448	BMS-754807	2
CHEMBL4094440	BMS-919373	2
CHEMBL1967878	CENISERTIB	2
CHEMBL12131	CLOSANTEL	2
CHEMBL4277900	CROZBACICLIB	2
CHEMBL4297488	CT-7001	2
CHEMBL5095094	CULMERCICLIB	2
CHEMBL3655762	CYC-065	2
CHEMBL402548	DANUSERTIB	2
CHEMBL4446357	EBVACICLIB	2
CHEMBL6246	ELLAGIC ACID	2
CHEMBL31574	FISETIN	2
CHEMBL1276127	INDIRUBIN	2
CHEMBL5095102	INIXACICLIB	2
CHEMBL5199065	ISTISOCICLIB	2
CHEMBL1980715	LAUROGUADINE	2
CHEMBL151	LUTEOLIN	2
CHEMBL362558	LY-2090314	2
CHEMBL3115681	NARAZACICLIB	2
CHEMBL475251	R-406	2
CHEMBL1738757	REBASTINIB	2
CHEMBL3545283	RIVICICLIB	2
CHEMBL4442620	RONICICLIB	2
CHEMBL23293	SALIRASIB	2
CHEMBL1230165	SILMITASERTIB	2
CHEMBL4297644	SIMUROSERTIB	2
CHEMBL565612	SOTRASTAURIN	2
CHEMBL5201870	TEGTOCICLIB	2

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CDK1 subfamily

Most potent curated ligand interactions (58 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
ECI830	Inhibition	7.82	pIC50

Binding affinities (BindingDB)

4683 measured of 6051 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL5088381	KD	0.03 nM
[(1R,3S)-3-[5-([1,3]thiazolo[4,5-b]pyridine-7-carbonylamino)pyrazolidin-3-yl]cyclopentyl] N-[(2S)-butan-2-yl]carbamate	KI	0.04 nM	US-11014911: CDK2 inhibitors
[(1R,3S)-3-[3-[(2-methylpyrazole-3-carbonyl)amino]-1H-pyrazol-5-yl]cyclopentyl] N-[(2S)-butan-2-yl]carbamate	KI	0.05 nM	US-11014911: CDK2 inhibitors
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
[(1R,3S)-3-[5-[[2-(2-methoxy-4-pyridinyl)acetyl]amino]pyrazolidin-3-yl]cyclopentyl] (2S,4S)-2,4-dimethylazetidine-1-carboxylate	KI	0.06 nM	US-11014911: CDK2 inhibitors
CHEMBL5080711	KD	0.06 nM
[(1R,3S)-3-[5-[[2-(2-methoxy-4-pyridinyl)acetyl]amino]pyrazolidin-3-yl]cyclopentyl] 2,2-dimethylazetidine-1-carboxylate	KI	0.07 nM	US-11014911: CDK2 inhibitors
[(1R,3S)-3-[3-[[2-(3-methyl-1,2-oxazol-5-yl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] 2-ethyl-2-methylazetidine-1-carboxylate	KI	0.07 nM	US-11014911: CDK2 inhibitors
CHEMBL566106	IC50	0.07 nM
CHEMBL4791134	KD	0.07 nM
6-(difluoromethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.08 nM
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
US10233188, Example 187	KI	0.08 nM	US-10233188: CDK2/4/6 inhibitors
[(1R,3S)-3-[5-[[2-(3,5-difluorophenyl)acetyl]amino]pyrazolidin-3-yl]cyclopentyl] N-(3-methyloxolan-3-yl)carbamate	KI	0.08 nM	US-11014911: CDK2 inhibitors
[(1R,3S)-3-[3-[[2-([1,2,4]triazolo[1,5-a]pyrimidin-6-yl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] (2S)-2-methylpyrrolidine-1-carboxylate	KI	0.08 nM	US-11014911: CDK2 inhibitors
CHEMBL568310	IC50	0.08 nM
CHEMBL4786592	KD	0.08 nM
CHEMBL4782954	KD	0.08 nM
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
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
(-)-6-(2,2-difluoroethyl)-8-[(1R*,2R*)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.09 nM	US-10800783: CDK2/4/6 inhibitors
[(1R,3S)-3-[5-[(3-methyltriazole-4-carbonyl)amino]pyrazolidin-3-yl]cyclopentyl] N-[(2S)-4,4,4-trifluorobutan-2-yl]carbamate	KI	0.09 nM	US-11014911: CDK2 inhibitors
[(1R,3S)-3-[5-[[2-(2-methoxy-4-pyridinyl)acetyl]amino]pyrazolidin-3-yl]cyclopentyl] N-(4,4-difluorobutan-2-yl)carbamate	KI	0.09 nM	US-11014911: CDK2 inhibitors
[(1R,3S)-3-[3-[[2-([1,2,4]triazolo[1,5-a]pyrimidin-6-yl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] 2,2-dimethylpyrrolidine-1-carboxylate	KI	0.09 nM	US-11014911: CDK2 inhibitors
CHEMBL567434	IC50	0.09 nM
CHEMBL5083688	KD	0.09 nM
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
[(1R,3S)-3-[5-[(3-methyltriazole-4-carbonyl)amino]pyrazolidin-3-yl]cyclopentyl] N-[(2S)-butan-2-yl]carbamate	KI	0.1 nM	US-11014911: CDK2 inhibitors
[(1R,3S)-3-[3-[[2-(2-hydroxyethyl)pyrazole-3-carbonyl]amino]-1H-pyrazol-5-yl]cyclopentyl] N-[(2S)-butan-2-yl]carbamate	KI	0.1 nM	US-11014911: CDK2 inhibitors
[(1R,3S)-3-[5-[[2-(1-methylindazol-5-yl)acetyl]amino]pyrazolidin-3-yl]cyclopentyl] N-propan-2-ylcarbamate	KI	0.1 nM	US-11014911: CDK2 inhibitors
[(1R,3S)-3-[5-[[2-(6-methyl-3-pyridinyl)acetyl]amino]pyrazolidin-3-yl]cyclopentyl] N-(4,4,4-trifluorobutan-2-yl)carbamate	KI	0.1 nM	US-11014911: CDK2 inhibitors
[(1R,3S)-3-[3-[[2-(1,3-oxazol-5-yl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] N-(4,4,4-trifluorobutan-2-yl)carbamate	KI	0.1 nM	US-11014911: CDK2 inhibitors
[(1R,3S)-3-[3-[[2-(1-methylpyrazol-4-yl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] N-[(2S)-4,4,4-trifluorobutan-2-yl]carbamate	KI	0.1 nM	US-11014911: CDK2 inhibitors
[(1R,3S)-3-[5-[[2-(6-methoxy-3-pyridinyl)acetyl]amino]pyrazolidin-3-yl]cyclopentyl] 2,2-dimethylazetidine-1-carboxylate	KI	0.1 nM	US-11014911: CDK2 inhibitors
CHEMBL565705	IC50	0.1 nM
CHEMBL566105	IC50	0.1 nM
CHEMBL568080	IC50	0.1 nM
CHEMBL583417	IC50	0.1 nM
CHEMBL4779443	KD	0.1 nM
CHEMBL4790490	KD	0.1 nM
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
[(1S,3R)-3-[5-[[2-(2-methyl-3H-benzimidazol-5-yl)acetyl]amino]pyrazolidin-3-yl]cyclopentyl] N-propylcarbamate	KI	0.11 nM	US-11014911: CDK2 inhibitors
[(1R,3S)-3-[5-[[2-(4-methyl-2-methylsulfonylphenyl)acetyl]amino]pyrazolidin-3-yl]cyclopentyl] N-[(2S)-butan-2-yl]carbamate	KI	0.11 nM	US-11014911: CDK2 inhibitors
[(1R,3S)-3-[5-[[2-(2-methylimidazo[1,2-b]pyridazin-6-yl)acetyl]amino]pyrazolidin-3-yl]cyclopentyl] N-[(2S)-butan-2-yl]carbamate	KI	0.11 nM	US-11014911: CDK2 inhibitors
[(1R,3S)-3-[3-[[2-(1-methylpyrazol-4-yl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] N-(2-methylbutan-2-yl)carbamate	KI	0.11 nM	US-11014911: CDK2 inhibitors
[(1R,3S)-3-[3-[[2-(3-methyl-1,2-oxazol-5-yl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] 2,2-dimethylpiperidine-1-carboxylate	KI	0.11 nM	US-11014911: CDK2 inhibitors

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

3037 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

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

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

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

9 cell lines: 7 cancer cell line, 2 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_F4Y4	EDITGENE CDK2 Knockout HEK293 Cell Line	Transformed 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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CDK2 across ~30M SureChEMBL compounds — explore on Sugi Predict.