CCNA2

Summary

CCNA2 (cyclin A2, HGNC:1578) is a protein-coding gene on chromosome 4q27, encoding Cyclin-A2 (P20248). Cyclin which controls both the G1/S and the G2/M transition phases of the cell cycle. It is a common-essential gene (DepMap: required in 98.8% of cancer cell lines).

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members function as regulators of the cell cycle. This protein binds and activates cyclin-dependent kinase 2 and thus promotes transition through G1/S and G2/M.

Source: NCBI Gene 890 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 140 total
• Druggable target: yes — 35 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_001237

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1578
Approved symbol	CCNA2
Name	cyclin A2
Location	4q27
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000145386
Ensembl biotype	protein_coding
OMIM	123835
Entrez	890

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000274026, ENST00000876644, ENST00000940444

RefSeq mRNA: 1 — MANE Select: NM_001237 NM_001237

CCDS: CCDS3723

Canonical transcript exons

ENST00000274026 — 8 exons

Exon	Start	End
ENSE00000970329	121820542	121820765
ENSE00000970330	121819372	121819579
ENSE00000970332	121822403	121822646
ENSE00000970333	121820979	121821091
ENSE00001016934	121818800	121818913
ENSE00001016935	121818044	121818177
ENSE00001176933	121816444	121817686
ENSE00001176937	121823416	121823883

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 97.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 336.1480 / max 3737.1604, expressed in 1532 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3828	336.1480	1532
53840	44.5724	1497
3829	1.1999	685

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.98	gold quality
oocyte	CL:0000023	96.97	gold quality
secondary oocyte	CL:0000655	95.38	gold quality
ganglionic eminence	UBERON:0004023	94.32	gold quality
embryo	UBERON:0000922	92.33	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.09	gold quality
endometrium epithelium	UBERON:0004811	87.93	gold quality
bone marrow	UBERON:0002371	85.58	gold quality
stromal cell of endometrium	CL:0002255	82.98	gold quality
lower esophagus mucosa	UBERON:0035834	82.90	gold quality
rectum	UBERON:0001052	82.87	gold quality
mucosa of transverse colon	UBERON:0004991	82.82	gold quality
trabecular bone tissue	UBERON:0002483	81.63	gold quality
vermiform appendix	UBERON:0001154	81.56	gold quality
esophagus mucosa	UBERON:0002469	81.01	gold quality
lymph node	UBERON:0000029	80.35	gold quality
thymus	UBERON:0002370	80.24	gold quality
adrenal tissue	UBERON:0018303	80.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.79	gold quality
sperm	CL:0000019	79.37	gold quality
tendon of biceps brachii	UBERON:0008188	79.23	gold quality
caecum	UBERON:0001153	79.06	gold quality
endometrium	UBERON:0001295	79.03	gold quality
duodenum	UBERON:0002114	78.12	gold quality
bone marrow cell	CL:0002092	78.10	gold quality
jejunal mucosa	UBERON:0000399	77.51	gold quality
male germ cell	CL:0000015	76.94	silver quality
oral cavity	UBERON:0000167	76.91	gold quality
amniotic fluid	UBERON:0000173	76.78	gold quality
esophagus	UBERON:0001043	75.36	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-79	yes	704.77
E-MTAB-6379	yes	375.58
E-GEOD-99795	yes	282.78
E-MTAB-9067	yes	243.73
E-MTAB-7249	yes	100.30
E-HCAD-10	yes	41.12
E-GEOD-125970	yes	17.32
E-ANND-3	yes	6.65
E-GEOD-75140	no	285.79
E-MTAB-9689	no	166.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF1, ATF2, ATF3, ATF4, BATF2, BCL6, CEBPA, CREB1, CREM, CUX1, DNMT1, E2F1, E2F3, E2F4, E4F1, EGR1, EPCAM, ESR1, ESR2, ETS1, EZH2, FOS, FOSL1, FOXG1, FOXM1, GATA4, HCFC1, HIF1A, HMGA2, ID2, JDP2, JUN, JUNB, KAT7, KLF5, KMT2A, KMT2E, MYC, NCOA1

miRNA regulators (miRDB)

106 targeting CCNA2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-5688	99.96	73.23	4504

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Centrosome overduplication, increased ploidy and transformation in cells expressing endoplasmic reticulum-associated cyclin A2 (PMID:11896577)
• found that cyclin A and cyclin E are able to regulate both nuclear and cytoplasmic events because they both shuttle between the nucleus and the cytoplasm (PMID:11907280)
• CDK-independent transactivation of the estrogen receptor by cyclin D1 is, by itself, not sufficient to cause estradiol-independent growth of breast cancer cells. A vast overexpression of G1/S cyclins D1 A & E is able to do so by capturing CDK inhibitors. (PMID:12444551)
• increases of cyclin D1, cyclin-dependent kinase 4, cyclin E, cyclin A, and Wee1 play an important role in the development of hepatocellular carcinoma from cirrhosis (PMID:12601350)
• B-Myb repressor function is regulated by cyclin A phosphorylation and sequences within the C-terminal domain. (PMID:12673206)
• cyclin A is important regulator for cell cycle as well as for apoptosis (PMID:12742823)
• mechanism of cyclin A2 degradation in mouse two-cell embryos may be different from that in somatic cells (PMID:14579410)
• HMGA2 associates with the E1A-regulated transcriptional repressor p120(E4F), interfering with p120(E4F) binding to the cyclin A promoter. (PMID:14645522)
• significant difference in their biochemical properties between CDK4/cyclin D1 and CDK2/cyclin A affecting regulation of cellular RB function (PMID:14646596)
• cyclin A bound tightly to Epstein-Barr virus nuclear antigen 3C (EBNA3C); EBNA3C interacted with cyclin A in vitro and associated with cyclin A complexes in EBV-transformed lymphoblastoid cell lines (PMID:14747563)
• Overexpression of cyclin A is unable to alter the nuclear localization of Cdc6 (PMID:14749377)
• IL-1beta reduces the ability of IGF-I to activate Cdk2 and to induce E2F-1, cyclin A, and cyclin A-dependent phosphorylation of a retinoblastoma tumor suppressor (PMID:15187102)
• cyclin A-cdk2 plays an ancillary noncatalytic role in the ubiquitination of p27(KIP1) by the SCF(skp2) complex (PMID:15199159)
• cyclin A/Cdk2 has a role as a progesterone receptor coactivator (PMID:15601848)
• Results demonstrate that a peptide derived from the alpha5 helix of cyclin A significantly inhibits kinase activity of complexes harboring CDK2, and forms stable complexes with CDK2-cyclin A. (PMID:15649889)
• HTm4 binding to KAP.Cdk2.cyclin A complex enhances the phosphatase activity of KAP, dissociates cyclin A, and facilitates KAP dephosphorylation of Cdk2 (PMID:15671017)
• It is considered that tumorigenesis with UC-associated dysplasia is of the bottom-up type, related to altered expression of cyclin A and p27(Kip1). (PMID:16398674)
• molecular analysis of the CDK5/p25 and CDK2/cyclin A systems (PMID:16407256)
• Here, we show that human papillomavirus type 16 16E1–E4 is also able to associate with cyclin A and Cdk2 during the G2 phase of the cell cycle. (PMID:16540140)
• Cyclin A overexpression was significantly associated with poor metastasis-free survival both on tissue microarrays and large sections in breast cancer. (PMID:16670718)
• Cyclin A is an independent prognostic factor in gastric cancer, and one mechanism for its overexpression may depend on cytoplasmic localization of HuR (PMID:16708383)
• Skp2-cyclin A interaction serves to directly protect cyclin A-cyclin-dependent kinase (Cdk)2 from inhibition by p27 through competitive binding. (PMID:16774918)
• Over-expression of cyclin A is associated with poor prognosis in breast cancer patients. (PMID:16823179)
• analysis of the NBI1-binding site on cyclin A which inhibits the catalytic activity of the complex cyclin-dependent kinase 2-cyclin A (PMID:17001081)
• Cyclin A plays a critical role in c-myc signal transduction to differentiall regulate the cell cycle in lung fibroblasts and epithelial cells. (PMID:17013808)
• Cyclin A2 is required for timely nuclear-envelope breakdown, whereas cyclins B1 and B2 are not. (PMID:17208191)
• Cyclin A may have a role in progression of Barrett’s esophagus to esophageal adenocarcinoma (PMID:17255290)
• There was a highly significant positive association between p27(KIP-1) and estrogen receptor/progesterone receptor (ER/PR) status and with p27(KIP-1) and cyclin D1 expression. A trend between cyclin A and PR status was also identified. (PMID:17316413)
• data strongly argue against mutational events of CDK1, cyclinB1 and cyclinA2 to play a role in gangliogliomas or focal cortical dysplasia (PMID:17359356)
• Raloxifene increased the proliferation of HUVECs in association with enhanced gene expression of cyclins A and B1. (PMID:17445807)
• The cyclin A recruitment site is used to recruit substrates containing an RXL motif. Because of sequence differences this site in cyclin A binds RXL motifs more strongly than in cyclin B. (PMID:17495531)
• epithelial component of the tumours expressed cyclin A in a statistically significantly higher number of carcinoma ex pleomorphic adenoma cases compared with the pleomorphic adenoma cases (PMID:17593077)
• These findings suggest novel Cdk1/cyclin A phosphorylation sites, which appear to be associated with p53-independent cell death following etoposide treatment. (PMID:17636382)
• Study describes the biochemically purification and identification of SCAPER, a novel protein that specifically interacts with cyclin A/Cdk2 in vivo. (PMID:17698606)
• Data demonstrated that in addition to galectin-3, HK III and cyclin A profiles could be important biomarkers in predicting malignancy in follicular thyroid nodules. (PMID:17868400)
• The enhanced expression of cyclin A was linked with cell proliferation in LSCC, ED, and NM. No association was observed between cyclin E and A and other clinicopathologic parameters. (PMID:17917837)
• Cyclin A2-siRNAs can induce obvious inhibition of cyclin A2 mRNA and protein expression in MG-63 and HSF cells, which consequently down-regulate the proliferation of MG-63 cells. (PMID:18246796)
• FBI-1 is the first transcriptional repressor shown to act as a dual regulator in adipogenesis exerting repressor activities on target genes by both, direct and indirect mechanisms. (PMID:18368381)
• JunB levels, which are high in S phase, drop during mid- to late G2 phase due to accelerated phosphorylation-dependent degradation by the proteasome, and are required for subsequent reduction of cyclin A2 levels in prometaphase (PMID:18391017)
• Data show that Cdc20 and Cks1 direct the spindle checkpoint-independent destruction of cyclin A2. (PMID:18471975)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccna2	ENSDARG00000011094
mus_musculus	Ccna2	ENSMUSG00000027715
rattus_norvegicus	Ccna2	ENSRNOG00000015423
drosophila_melanogaster	CycB	FBGN0000405
drosophila_melanogaster	CycD	FBGN0010315
drosophila_melanogaster	CycE	FBGN0010382
caenorhabditis_elegans		WBGENE00000865
caenorhabditis_elegans		WBGENE00000866
caenorhabditis_elegans	cyb-2.2	WBGENE00000867
caenorhabditis_elegans		WBGENE00000870
caenorhabditis_elegans	cye-1	WBGENE00000871

Paralogs (18): CCNE1 (ENSG00000105173), CCNP (ENSG00000105219), CCNJ (ENSG00000107443), CCND1 (ENSG00000110092), CCND3 (ENSG00000112576), CCNG1 (ENSG00000113328), CCNI (ENSG00000118816), CCND2 (ENSG00000118971), CCNA1 (ENSG00000133101), CCNB1 (ENSG00000134057), CCNJL (ENSG00000135083), CCNG2 (ENSG00000138764), CCNB3 (ENSG00000147082), CCNO (ENSG00000152669), CCNB2 (ENSG00000157456), CCNF (ENSG00000162063), CCNE2 (ENSG00000175305), CCNI2 (ENSG00000205089)

Protein

Protein identifiers

Cyclin-A2 — P20248 (reviewed: P20248)

Alternative names: Cyclin A

All UniProt accessions (1): P20248

UniProt curated annotations — full annotation on UniProt →

Function. Cyclin which controls both the G1/S and the G2/M transition phases of the cell cycle. Functions through the formation of specific serine/threonine protein kinase holoenzyme complexes with the cyclin-dependent protein kinases CDK1 or CDK2. The cyclin subunit confers the substrate specificity of these complexes and differentially interacts with and activates CDK1 and CDK2 throughout the cell cycle.

Subunit / interactions. Interacts with the CDK1 and CDK2 protein kinases to form serine/threonine kinase holoenzyme complexes. Interacts with CDK1 (hyperphosphorylated form in G1 and underphosphorylated forms in S and G2). Interacts with CDK2; the interaction increases from G1 to G2. Interacts (associated with CDK2 but not with CDK1) with SCAPER; regulates the activity of CCNA2/CDK2 by transiently maintaining CCNA2 in the cytoplasm. Forms a ternary complex with CDK2 and CDKN1B; CDKN1B inhibits the kinase activity of CDK2 through conformational rearrangements. Interacts with INCA1. (Microbial infection) Interacts with human cytomegalovirus protein UL32.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. Polyubiquitinated via ‘Lys-11’-linked ubiquitin by the anaphase-promoting complex (APC/C), leading to its degradation by the proteasome. Deubiquitinated and stabilized by USP37 enables entry into S phase. Ubiquitinated during the G1 phase by the SCF(FBXO31) complex, leading to its proteasomal degradation.

Similarity. Belongs to the cyclin family. Cyclin AB subfamily.

RefSeq proteins (1): NP_001228* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004367	Cyclin_C-dom	Domain
IPR006671	Cyclin_N	Domain
IPR013763	Cyclin-like_dom	Domain
IPR032447	Cyclin-A_N	Domain
IPR036915	Cyclin-like_sf	Homologous_superfamily
IPR039361	Cyclin	Family
IPR046965	Cyclin_A/B-like	Family
IPR048258	Cyclins_cyclin-box	Conserved_site

Pfam: PF00134, PF02984, PF16500

UniProt features (37 total): helix 19, strand 6, turn 4, modified residue 3, region of interest 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

114 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9D97	X-RAY DIFFRACTION	1.6
4EOJ	X-RAY DIFFRACTION	1.65
2CCH	X-RAY DIFFRACTION	1.7
7QHL	X-RAY DIFFRACTION	1.7
7ACK	X-RAY DIFFRACTION	1.8
6ATH	X-RAY DIFFRACTION	1.82
4EOP	X-RAY DIFFRACTION	1.99
1H1R	X-RAY DIFFRACTION	2
1H1S	X-RAY DIFFRACTION	2
1OIU	X-RAY DIFFRACTION	2
2IW9	X-RAY DIFFRACTION	2
4CFV	X-RAY DIFFRACTION	2
4EOI	X-RAY DIFFRACTION	2
5CYI	X-RAY DIFFRACTION	2
4BCK	X-RAY DIFFRACTION	2.05
2UUE	X-RAY DIFFRACTION	2.06
1H1P	X-RAY DIFFRACTION	2.1
1OI9	X-RAY DIFFRACTION	2.1
2C5N	X-RAY DIFFRACTION	2.1
2C5O	X-RAY DIFFRACTION	2.1
4BCN	X-RAY DIFFRACTION	2.1
4EOM	X-RAY DIFFRACTION	2.1
4EOO	X-RAY DIFFRACTION	2.1
4EOQ	X-RAY DIFFRACTION	2.15
6GVA	X-RAY DIFFRACTION	2.15
9GLA	X-RAY DIFFRACTION	2.18
1H27	X-RAY DIFFRACTION	2.2
1QMZ	X-RAY DIFFRACTION	2.2
4CFN	X-RAY DIFFRACTION	2.2
4CFU	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20248-F1	73.80	0.59

Functional residue map

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

Post-translational modifications (3): 1, 5, 55

Function

Pathways and Gene Ontology

Reactome pathways

61 pathways

ID	Pathway
R-HSA-1362300	Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1
R-HSA-1538133	G0 and Early G1
R-HSA-171319	Telomere Extension By Telomerase
R-HSA-174184	Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-HSA-176408	Regulation of APC/C activators between G1/S and early anaphase
R-HSA-187577	SCF(Skp2)-mediated degradation of p27/p21
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2559586	DNA Damage/Telomere Stress Induced Senescence
R-HSA-5689880	Ub-specific processing proteases
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-6804116	TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-6804757	Regulation of TP53 Degradation
R-HSA-68911	G2 Phase
R-HSA-68949	Orc1 removal from chromatin
R-HSA-69017	CDK-mediated phosphorylation and removal of Cdc6
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-69478	G2/M DNA replication checkpoint
R-HSA-69563	p53-Dependent G1 DNA Damage Response
R-HSA-69656	Cyclin A:Cdk2-associated events at S phase entry
R-HSA-75035	Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
R-HSA-157579	Telomere Maintenance
R-HSA-1640170	Cell Cycle
R-HSA-170145
R-HSA-174143	APC/C-mediated degradation of cell cycle proteins
R-HSA-176409	APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-176814	Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-179419	APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint
R-HSA-180786	Extension of Telomeres
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 1124 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD8_TCELL_UP, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, ATF_B, GNF2_CKS1B, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, REACTOME_DNA_REPLICATION, MODULE_52, TSUNODA_CISPLATIN_RESISTANCE_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, HORIUCHI_WTAP_TARGETS_DN

GO Biological Process (24): G1/S transition of mitotic cell cycle (GO:0000082), G2/M transition of mitotic cell cycle (GO:0000086), regulation of DNA replication (GO:0006275), DNA-templated transcription (GO:0006351), Ras protein signal transduction (GO:0007265), animal organ regeneration (GO:0031100), response to glucagon (GO:0033762), cellular response to platelet-derived growth factor stimulus (GO:0036120), post-translational protein modification (GO:0043687), cellular response to leptin stimulus (GO:0044320), cell cycle G1/S phase transition (GO:0044843), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of fibroblast proliferation (GO:0048146), cell division (GO:0051301), cellular response to cocaine (GO:0071314), cellular response to luteinizing hormone stimulus (GO:0071373), cellular response to estradiol stimulus (GO:0071392), cellular response to hypoxia (GO:0071456), cellular response to nitric oxide (GO:0071732), cochlea development (GO:0090102), cellular response to insulin-like growth factor stimulus (GO:1990314), positive regulation of DNA biosynthetic process (GO:2000573), response to estradiol (GO:0032355), mitotic cell cycle phase transition (GO:0044772)

GO Molecular Function (4): cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538), protein kinase binding (GO:0019901), protein domain specific binding (GO:0019904), protein binding (GO:0005515)

GO Cellular Component (10): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), female pronucleus (GO:0001939), male pronucleus (GO:0001940), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytosol (GO:0005829), cyclin A2-CDK1 complex (GO:0097122), cyclin A2-CDK2 complex (GO:0097124)

Reactome top-level categories

Rollup of top-19 pathways:

Category	Pathways
Cellular Senescence	2
Switching of origins to a post-replicative state	2
G0 and Early G1	1
Mitotic G1 phase and G1/S transition	1
Extension of Telomeres	1
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	1
APC/C-mediated degradation of cell cycle proteins	1
Cyclin E associated events during G1/S transition	1
Cyclin A:Cdk2-associated events at S phase entry	1
Deubiquitination	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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular response to oxygen-containing compound	3
mitotic cell cycle	2
mitotic cell cycle phase transition	2
pronucleus	2
cyclin-dependent protein kinase holoenzyme complex	2
cell cycle G1/S phase transition	1
cell cycle G2/M phase transition	1
DNA replication	1
regulation of DNA metabolic process	1
gene expression	1
RNA biosynthetic process	1
small GTPase-mediated signal transduction	1
regeneration	1
animal organ development	1
response to peptide hormone	1
response to platelet-derived growth factor	1
cellular response to growth factor stimulus	1
protein modification process	1
cellular response to hormone stimulus	1
response to leptin	1
cell cycle phase transition	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
positive regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
cellular process	1
response to cocaine	1
cellular response to alkaloid	1
response to luteinizing hormone	1
cellular response to gonadotropin stimulus	1
cellular response to peptide hormone stimulus	1
response to estradiol	1
cellular response to lipid	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
response to nitric oxide	1

Protein interactions and networks

STRING

4876 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCNA2	CDK2	P24941	999
CCNA2	SKP2	Q13309	998
CCNA2	CDK1	P06493	998
CCNA2	CDKN1B	P46527	997
CCNA2	CDK4	P11802	996
CCNA2	CDKN1A	P38936	996
CCNA2	CDK6	Q00534	994
CCNA2	TP53	P04637	994
CCNA2	E2F1	Q01094	989
CCNA2	CDC20	Q12834	970
CCNA2	SKP1	P34991	964
CCNA2	CCNL2	Q96S94	958
CCNA2	CDC25B	P30305	946
CCNA2	CDC6	Q99741	941
CCNA2	CDKN1C	P49918	928

IntAct

150 interactions, top by confidence:

A	B	Type	Score
CCNA2	CDK2	psi-mi:“MI:0915”(physical association)	0.980
CCNA2	CDK2	psi-mi:“MI:0407”(direct interaction)	0.980
CDK2	CCNA2	psi-mi:“MI:0407”(direct interaction)	0.980
CCNA2	CDK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.980
CDK2	CCNA2	psi-mi:“MI:0914”(association)	0.980
CDC20	BUB1B	psi-mi:“MI:0914”(association)	0.980
CCNA2	CDK2	psi-mi:“MI:0914”(association)	0.980
CDKN1B	CCNA2	psi-mi:“MI:0915”(physical association)	0.970
CCNA2	CDKN1B	psi-mi:“MI:0407”(direct interaction)	0.970
CCNA2	CDKN1B	psi-mi:“MI:0915”(physical association)	0.970
CDKN1B	CCNA2	psi-mi:“MI:0407”(direct interaction)	0.970
CDK2	CCNE2	psi-mi:“MI:0914”(association)	0.940

BioGRID (519): CCNA2 (Biochemical Activity), CCNA2 (Affinity Capture-Western), CCNA2 (Biochemical Activity), CDK2 (Affinity Capture-Western), CDC20 (Affinity Capture-Western), FZR1 (Affinity Capture-Western), CDC27 (Affinity Capture-Western), CKS1B (Affinity Capture-Western), CKS2 (Affinity Capture-Western), CDK1 (Affinity Capture-Western), CKS1BP7 (Affinity Capture-Western), CCNA2 (Affinity Capture-Western), CCNA2 (Affinity Capture-Western), CCNA2 (Affinity Capture-MS), CCNA2 (Affinity Capture-MS)

ESM2 similar proteins: A0MEB5, A2YH60, O14332, O48790, P04962, P07818, P18606, P20248, P24861, P24865, P25010, P30183, P30274, P30278, P34801, P36630, P37881, P39963, P43449, P46277, P46278, P47827, P51943, P51988, Q01J96, Q0D9C7, Q0DJR9, Q0JIF2, Q10653, Q10654, Q147G5, Q38819, Q39067, Q39068, Q39069, Q39070, Q39071, Q3ECW2, Q61456, Q6AY13

Diamond homologs: A0MEB5, A2YH60, O48790, O77689, O93229, O95067, P04962, P07818, P10815, P13350, P13351, P13952, P14635, P14785, P15206, P18606, P20248, P20439, P24860, P24861, P24862, P24871, P25010, P25011, P25012, P29332, P30183, P30274, P30276, P30277, P30278, P30284, P34800, P34801, P37881, P37882, P37883, P39963, P42524, P43449

SIGNOR signaling

18 interactions.

A	Effect	B	Mechanism
MYC	“up-regulates quantity by expression”	CCNA2	“transcriptional regulation”
HMGA2	“up-regulates quantity by expression”	CCNA2	“transcriptional regulation”
CCNA2	“form complex”	CyclinA2/CDK2	binding
4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-pyrazole-3-carboxamide	down-regulates	CCNA2	“chemical inhibition”
4-[[5-amino-1-[(2,6-difluorophenyl)-oxomethyl]-1,2,4-triazol-3-yl]amino]benzenesulfonamide	down-regulates	CCNA2	“chemical inhibition”
PHA-848125	down-regulates	CCNA2	“chemical inhibition”
seliciclib	down-regulates	CCNA2	“chemical inhibition”
USP37	“up-regulates quantity by stabilization”	CCNA2	deubiquitination
CCNA2	“form complex”	CyclinA2/CDK1	binding
NEK5	“up-regulates activity”	CCNA2	binding
CDC25A	“up-regulates activity”	CCNA2	dephosphorylation
TGFB1	“down-regulates quantity by repression”	CCNA2	“transcriptional regulation”
CDK2	up-regulates	CCNA2	phosphorylation
SMARCB1	down-regulates	CCNA2
APC-c	“down-regulates quantity by destabilization”	CCNA2	ubiquitination
CCNA2	“form complex”	CyclinA2/CDK18	binding
YAP1	“up-regulates quantity by expression”	CCNA2	“transcriptional regulation”
YAP/TAZ	“up-regulates quantity by expression”	CCNA2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 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)	7	52.9×	2e-09
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	6	51.0×	4e-08
TP53 Regulates Transcription of Cell Cycle Genes	7	45.3×	5e-09
Cyclin A:Cdk2-associated events at S phase entry	14	44.3×	1e-17
Cyclin E associated events during G1/S transition	13	44.2×	1e-16
p53-Dependent G1 DNA Damage Response	5	42.5×	2e-06
p53-Dependent G1/S DNA damage checkpoint	5	42.5×	2e-06
G1/S Transition	15	41.6×	2e-18

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of DNA replication	6	34.5×	4e-06
G1/S transition of mitotic cell cycle	13	25.8×	2e-12
mitotic G2 DNA damage checkpoint signaling	5	21.9×	4e-04
regulation of mitotic cell cycle	8	19.1×	3e-06
G2/M transition of mitotic cell cycle	6	18.5×	2e-04
regulation of G1/S transition of mitotic cell cycle	5	15.2×	2e-03
cell division	21	9.6×	2e-12
regulation of cell cycle	8	5.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	91
Likely benign	8
Benign	21

Top pathogenic / likely-pathogenic (0)

SpliceAI

1248 predictions. Top by Δscore:

Variant	Effect	Δscore
1:85581047:GGT:G	donor_loss	1.0000
1:85581048:G:GG	donor_gain	1.0000
1:85581048:GTG:G	donor_loss	1.0000
1:85581360:TCCA:T	acceptor_loss	1.0000
1:85581362:CAGGC:C	acceptor_loss	1.0000
1:85581363:A:AG	acceptor_gain	1.0000
1:85581363:AG:A	acceptor_gain	1.0000
1:85581363:AGGC:A	acceptor_gain	1.0000
1:85581364:G:GT	acceptor_gain	1.0000
1:85581364:GG:G	acceptor_gain	1.0000
1:85581364:GGC:G	acceptor_gain	1.0000
1:85581364:GGCG:G	acceptor_gain	1.0000
1:85581364:GGCGC:G	acceptor_gain	1.0000
1:85581576:GAG:G	donor_gain	1.0000
1:85581578:GGTAA:G	donor_loss	1.0000
1:85581579:G:GG	donor_gain	1.0000
1:85581579:GTAA:G	donor_loss	1.0000
1:85581580:T:A	donor_loss	1.0000
1:85581913:T:TA	acceptor_gain	1.0000
1:85581914:G:A	acceptor_gain	1.0000
1:85581916:T:TA	acceptor_gain	1.0000
1:85582285:G:GA	donor_loss	1.0000
1:85582285:G:GG	donor_gain	1.0000
1:85582407:T:G	acceptor_gain	1.0000
1:85582411:TCTA:T	acceptor_loss	1.0000
1:85582413:TAGT:T	acceptor_loss	1.0000
1:85582414:A:AG	acceptor_gain	1.0000
1:85582415:G:GC	acceptor_gain	1.0000
1:85582415:GT:G	acceptor_gain	1.0000
1:85582415:GTT:G	acceptor_gain	1.0000

AlphaMissense

2811 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:121819462:A:C	F304L	1.000
4:121819462:A:T	F304L	1.000
4:121819464:A:G	F304L	1.000
4:121819469:A:G	L302P	1.000
4:121819484:A:G	L297P	1.000
4:121819489:C:A	E295D	1.000
4:121819489:C:G	E295D	1.000
4:121819490:T:A	E295V	1.000
4:121819492:C:A	M294I	1.000
4:121819492:C:G	M294I	1.000
4:121819492:C:T	M294I	1.000
4:121819499:A:G	L292P	1.000
4:121819502:A:T	V291D	1.000
4:121819518:A:C	Y286D	1.000
4:121819532:A:T	I281N	1.000
4:121819576:C:A	K266N	1.000
4:121819576:C:G	K266N	1.000
4:121819578:T:C	K266E	1.000
4:121820543:A:G	S265P	1.000
4:121820545:G:T	A264D	1.000
4:121820551:A:G	L262P	1.000
4:121820560:G:T	A259D	1.000
4:121820566:C:T	G257D	1.000
4:121820567:C:G	G257R	1.000
4:121820572:A:G	L255P	1.000
4:121820572:A:T	L255H	1.000
4:121820574:C:A	Q254H	1.000
4:121820574:C:G	Q254H	1.000
4:121820578:A:G	L253P	1.000
4:121820578:A:T	L253H	1.000

dbSNP variants (sampled 300 via entrez): RS1000702281 (4:121819259 A>G), RS1000941411 (4:121816724 C>G,T), RS1001375495 (4:121822883 A>T), RS1001616976 (4:121816600 T>G), RS1002279177 (4:121823798 G>A), RS1002344670 (4:121823931 T>C), RS1003052321 (4:121824033 G>A), RS1003249924 (4:121817606 A>C,T), RS1003271738 (4:121824427 C>A), RS1003283920 (4:121821794 T>C,G), RS1003836162 (4:121817845 A>G), RS1004509572 (4:121819703 A>C,G,T), RS1004784925 (4:121820842 C>A,T), RS1004859986 (4:121819127 C>A,T), RS1005108380 (4:121819151 A>G)

Disease associations

OMIM: gene MIM:123835 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST90000025_931	Appendicular lean mass	5.000000e-12
GCST90000026_2	Appendicular lean mass	5.000000e-06
GCST90000027_27	Appendicular lean mass	2.000000e-07
GCST90002390_220	Mean corpuscular hemoglobin	3.000000e-51

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL2094128 (PROTEIN COMPLEX), CHEMBL2582 (SINGLE PROTEIN), CHEMBL3038467 (PROTEIN COMPLEX), CHEMBL3038469 (PROTEIN COMPLEX), CHEMBL4523636 (PROTEIN COMPLEX), CHEMBL5483182 (PROTEIN COMPLEX GROUP), CHEMBL6195578 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

35 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 191,373 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL3545110	RIBOCICLIB	4	8,018
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL407874	6-O-BENZYLGUANINE	3	6,988
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL14762	SELICICLIB	2	3,787
CHEMBL1944698	ZOTIRACICLIB	2	2,915
CHEMBL2347597	ASNUCICLIB	2	100
CHEMBL3545283	RIVICICLIB	2	968
CHEMBL445813	AT-7519	2	2,614
CHEMBL565612	SOTRASTAURIN	2	1,355
CHEMBL6246	ELLAGIC ACID	2	23,148
CHEMBL4277900	CROZBACICLIB	2	18
CHEMBL4446357	EBVACICLIB	2	599
CHEMBL5199065	ISTISOCICLIB	2	21
CHEMBL5201870	TEGTOCICLIB	2	23
CHEMBL1276127	INDIRUBIN	2
CHEMBL3115681	NARAZACICLIB	2
CHEMBL3655762	CYC-065	2
CHEMBL4067549	ULECACICLIB	2
CHEMBL5095102	INIXACICLIB	2
CHEMBL564829	MILCICLIB	2
CHEMBL1230607	PHA-793887	1
CHEMBL269538	HARMINE	1
CHEMBL4439321	ATUVECICLIB	1
CHEMBL488436	AZD-5438	1

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

Binding affinities (BindingDB)

706 measured of 1078 human assays (1084 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-(4-sulfamoylphenyl)-3,4,10,11-tetraazatricyclo[7.3.0.0^{2,6}]dodeca-1(9),2(6),4,7,11-pentaene-5-carboxamide	IC50	0.3 nM
4-{[3-(4-nitrophenyl)-1H-pyrazol-5-yl]amino}benzene-1-sulfonamide	IC50	0.33 nM
4-{[3-(4-aminophenyl)-1H-pyrazol-5-yl]amino}benzene-1-sulfonamide	IC50	0.34 nM
(12Z)-12-{[(4-{[2-(2-hydroxyethoxy)ethyl]sulfamoyl}phenyl)amino]methylidene}-3-thia-5,10-diazatricyclo[7.3.0.0^{2,6}]dodeca-1,4,6,8-tetraen-11-one	IC50	0.54 nM
erk000526	KI	1 nM
3-(4-methanesulfonylphenyl)-3,4,10,11-tetraazatricyclo[7.3.0.0^{2,6}]dodeca-1(9),2(6),4,7,11-pentaene-5-carboxamide	IC50	1 nM
N-methyl-4-({[(12Z)-11-oxo-3-thia-5,10-diazatricyclo[7.3.0.0^{2,6}]dodeca-1,4,6,8-tetraen-12-ylidene]methyl}amino)-N-(2,5,8,11-tetraoxatridecan-13-yl)benzene-1-sulfonamide	IC50	1 nM
4-[(4-{pyrazolo[1,5-a]pyridazin-3-yl}pyrimidin-2-yl)amino]benzonitrile	IC50	1 nM
N-(3,4-dichlorophenyl)-4-{pyrazolo[1,5-a]pyridazin-3-yl}pyrimidin-2-amine	IC50	1 nM
N-(3,5-difluorophenyl)-4-{pyrazolo[1,5-a]pyridazin-3-yl}pyrimidin-2-amine	IC50	1 nM
4-{[4-amino-6-(cyclohexylmethoxy)-5-nitrosopyrimidin-2-yl]amino}benzene-1-sulfonamide	IC50	1.1 nM
4-{2-[(3Z)-4-(2-methylpropyl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzene-1-sulfonamide	IC50	1.2 nM
1-(2,6-difluorophenyl)-3-{3-[5-(morpholin-4-ylmethyl)-1H-1,3-benzodiazol-2-yl]-1H-pyrazol-4-yl}urea	IC50	1.5 nM
4-{2-[(3Z)-4-(2-methylprop-1-en-1-yl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzene-1-sulfonamide	IC50	1.5 nM
4-({[(3Z)-4-oxo-5,10-diazatricyclo[7.4.0.0^{2,6}]trideca-1,6,8,10,12-pentaen-3-ylidene]methyl}amino)benzene-1-sulfonamide	IC50	1.5 nM
4-[N -2-Oxo-2,3-dihydropyrrolo[3,2-f]quinolin-1-ylidene)-hydrazino]benzenesulfonamide	IC50	1.6 nM
3-{[4-(Aminosulfonyl)phenyl]hydrazono}-N-(2,6-dimethoxybenzyl)-2-oxo-5-indolinecarboxamide	IC50	1.7 nM
2-((5-bromo-2-((4-(N-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)-2-oxo-6,9,12,15-tetraoxa-3-azaheptadecan-17-yl)sulfamoyl)-2-methylphenyl)amino)pyrimidin-4-yl)amino)-6-fluorobenzamide	IC50	1.7 nM	US-12466809: CDK2/5 degraders and uses thereof
4-({[(3Z)-5-(3-methylbutanoyl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}amino)benzene-1-sulfonamide	IC50	1.9 nM
4-({5-[(4-aminocyclohexyl)amino]-3-bromopyrazolo[1,5-a]pyrimidin-7-yl}amino)-2-chloro-N,N-dimethylbenzene-1-sulfonamide	IC50	2 nM
(2S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-[4-(1-oxo-2,3-dihydro-1H-isoindol-2-yl)phenyl]propanamide	IC50	2 nM
(2S)-N-(5-Cyclopropyl-1H-pyrazol-3-yl)-2-[4-(2-oxoimidazolidin-1-yl)phenyl]propanamide	IC50	2 nM
3-[4-(methylsulfamoyl)phenyl]-3,4,10,11-tetraazatricyclo[7.3.0.0^{2,6}]dodeca-1(9),2(6),4,7,11-pentaene-5-carboxamide	IC50	2 nM
3-[4-(butylsulfamoyl)phenyl]-3,4,10,11-tetraazatricyclo[7.3.0.0^{2,6}]dodeca-1(9),2(6),4,7,11-pentaene-5-carboxamide	IC50	2 nM
3-(2,2,2-trifluoroethyl)-3,4,10,11-tetraazatricyclo[7.3.0.0^{2,6}]dodeca-1(9),2(6),4,7,11-pentaene-5-carboxamide	IC50	2 nM
4-[1-(5-Oxazol-5-yl-2-oxo-1,2-dihydro-indol-3-ylidene)-ethylamino]benzenesulfonamide	IC50	2 nM
2-((5-bromo-2-((4-(N-(4-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperazin-1-yl)butyl)sulfamoyl)-2-methylphenyl)amino)pyrimidin-4-yl)amino)-6-fluorobenzamide	IC50	2 nM	US-12466809: CDK2/5 degraders and uses thereof
N-(3-methoxyphenyl)-4-{pyrazolo[1,5-a]pyridazin-3-yl}pyrimidin-2-amine	IC50	2 nM
N-(3,4-difluorophenyl)-4-{pyrazolo[1,5-a]pyridazin-3-yl}pyrimidin-2-amine	IC50	2 nM
N-[6-(3-bromo-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide	IC50	2 nM
N-[6-(3-chloro-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide	IC50	2 nM
methyl (3Z)-2-oxo-3-{[(4-sulfamoylphenyl)amino]methylidene}-2,3-dihydro-1H-indole-5-carboxylate	IC50	2.1 nM
3-{[4-(Aminosulfonyl)phenyl]hydrazono}-2-oxo-N-(3-pyridinylmethyl)-2,3-dihydro-1H-indole-5-carboxamide	IC50	2.1 nM
4-[N -(1-Chloro-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-e]indazol-8-ylidene)-hydrazino]benzenesulfonamide	IC50	2.2 nM
4-{2-[(3Z)-5-(1,3-oxazol-5-yl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzene-1-sulfonamide	IC50	2.3 nM
4-({[(3Z)-5-(1,3-oxazol-5-yl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}amino)benzene-1-sulfonamide	IC50	2.5 nM
4-[N’-(4-Isopropyl-2-oxo-1,2-dihydro-indol-3-ylidene)-hydrazino]benzenesulfonamide	IC50	2.5 nM
1-(2-fluorophenyl)-3-{3-[5-(morpholin-4-ylmethyl)-1H-1,3-benzodiazol-2-yl]-1H-pyrazol-4-yl}urea	IC50	2.8 nM
4-({[(12Z)-11-oxo-3-thia-5,10-diazatricyclo[7.3.0.0^{2,6}]dodeca-1,4,6,8-tetraen-12-ylidene]methyl}amino)benzene-1-sulfonamide	IC50	2.8 nM
4-N-(2,6-difluorobenzene)-3-N-(4-fluorophenyl)-1H-pyrazole-3,4-diamido	IC50	3 nM
erk000524	KI	3 nM
erk000617	KI	3 nM
CS10	IC50	3 nM
Isobutyl 3-{[4-(aminosulfonyl)anilino]methylene}-2-oxo-2,3-dihydro-1H-indole-5-carboxylate	IC50	3 nM
N-(3,5-dimethylphenyl)-4-{pyrazolo[1,5-a]pyridazin-3-yl}pyrimidin-2-amine	IC50	3 nM
8-{[4-({[Amino(imino)methyl]amino}sulfonyl)anilino]-methylene}-7-oxo-7,8-dihydro-6H-[1,3]thiazolo[5,4-e]indole	IC50	3.3 nM
4-{2-[(3Z)-2-oxo-4-(propan-2-yloxy)-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzene-1-sulfonamide	IC50	3.4 nM
N-{3-[5-(morpholin-4-ylmethyl)-1H-1,3-benzodiazol-2-yl]-1H-pyrazol-4-yl}benzamide	IC50	3.5 nM
N-[2-(1H-imidazol-5-yl)ethyl]-4-({[(12Z)-11-oxo-3-thia-5,10-diazatricyclo[7.3.0.0^{2,6}]dodeca-1,4,6,8-tetraen-12-ylidene]methyl}amino)benzene-1-sulfonamide	IC50	3.6 nM
N1-(2-((4-((5-bromo-4-((2-carbamoyl-3-fluorophenyl)amino)pyrimidin-2-yl)amino)piperidin-1-yl)sulfonyl)ethyl)-N4-(5-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)succinamide	IC50	3.8 nM	US-12466809: CDK2/5 degraders and uses thereof

ChEMBL bioactivities

2379 potent at pChembl≥5 of 2681 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.80	IC50	0.16	nM	CHEMBL5808524
9.70	Ki	0.2	nM	CHEMBL2312187
9.70	IC50	0.2	nM	CHEMBL261720
9.52	IC50	0.3	nM	CHEMBL360520
9.52	IC50	0.3	nM	CHEMBL363607
9.40	IC50	0.4	nM	STAUROSPORINE
9.40	IC50	0.4	nM	CHEMBL363130
9.40	IC50	0.4	nM	CHEMBL5837976
9.30	IC50	0.5	nM	CHEMBL261720
9.22	IC50	0.6	nM	CHEMBL382690
9.22	IC50	0.6	nM	STAUROSPORINE
9.22	IC50	0.6	nM	CHEMBL5739950
9.15	IC50	0.7	nM	CHEMBL4590821
9.15	IC50	0.7	nM	CHEMBL4848734
9.15	IC50	0.7	nM	SELICICLIB
9.15	IC50	0.7	nM	CHEMBL5803114
9.14	IC50	0.72	nM	STAUROSPORINE
9.14	IC50	0.727	nM	STAUROSPORINE
9.05	IC50	0.9	nM	CHEMBL2377864
9.00	Ki	1	nM	CHEMBL2312182
9.00	Ki	1	nM	CHEMBL2348844
9.00	IC50	1	nM	CHEMBL361595
9.00	IC50	1	nM	DINACICLIB
9.00	IC50	1	nM	CHEMBL3897452
9.00	IC50	1	nM	CHEMBL4101278
9.00	IC50	1	nM	CHEMBL560817
9.00	IC50	1	nM	STAUROSPORINE
9.00	IC50	1	nM	CHEMBL5747791
9.00	IC50	1	nM	CHEMBL5776705
9.00	IC50	1	nM	CHEMBL5938366
9.00	IC50	1	nM	CHEMBL597753
9.00	IC50	1	nM	CHEMBL598401
9.00	IC50	1	nM	CHEMBL1270713
9.00	IC50	1	nM	CHEMBL1270818
9.00	IC50	1	nM	CHEMBL1271330
8.96	IC50	1.1	nM	CHEMBL2377825
8.82	Ki	1.5	nM	CHEMBL2348843
8.82	IC50	1.5	nM	CHEMBL2377825
8.80	IC50	1.6	nM	GW305178X
8.77	IC50	1.7	nM	STAUROSPORINE
8.77	IC50	1.7	nM	CHEMBL5797283
8.74	Kd	1.8	nM	CHEMBL3409600
8.71	IC50	1.93	nM	STAUROSPORINE
8.70	Ki	2	nM	CHEMBL2348846
8.70	Ki	2	nM	CHEMBL2348842
8.70	IC50	2	nM	CHEMBL181036
8.70	IC50	2	nM	CHEMBL182209
8.70	IC50	2	nM	CHEMBL181616
8.70	IC50	2	nM	JNJ-7706621
8.70	IC50	2	nM	CHEMBL190446

PubChem BioAssay actives

2489 with measured affinity, of 5243 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-[[5-cyano-4-[4-methyl-2-(methylamino)-1,3-thiazol-5-yl]pyrimidin-2-yl]amino]benzenesulfonamide	723734: Inhibition of CDK2/Cyclin A (174 to 432 amino acid residues) (unknown origin) by differential scanning fluorimetry assay	ki	0.0002	uM
5-amino-N-(2,6-difluorophenyl)-3-(4-sulfamoylanilino)-1,2,4-triazole-1-carbothioamide	1513681: Inhibition of GST-tagged CDK2/cyclin A2 (unknown origin) expressed in Escherichia coli using histone H1 as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay	ic50	0.0002	uM
4-[[1-(2,6-difluoro-3-methylbenzoyl)-5-methyl-1,2,4-triazol-3-yl]amino]benzenesulfonamide	241015: Inhibition of Cyclin-dependent kinase 2-cyclin A	ic50	0.0003	uM
4-[[5-amino-1-(2,6-difluoro-3-methylbenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities.”	ic50	0.0003	uM
1-(4-sulfamoylphenyl)-2H-pyrazolo[3,4-e]indazole-3-carboxamide	1795998: Kinase SPA Assay from Article 10.1016/j.bmcl.2005.01.023: “Benzodipyrazoles: a new class of potent CDK2 inhibitors.”	ic50	0.0003	uM
4-[[5-(4-aminophenyl)-1H-pyrazol-3-yl]amino]benzenesulfonamide	1796189: Kinase Inhibition SPA Assay from Article 10.1016/s0960-894x(03)00630-9: “Anilinopyrazole as selective CDK2 inhibitors: design, synthesis, biological evaluation, and X-ray crystallographic analysis.”	ic50	0.0003	uM
4-[[5-(4-nitrophenyl)-1H-pyrazol-3-yl]amino]benzenesulfonamide	1796189: Kinase Inhibition SPA Assay from Article 10.1016/s0960-894x(03)00630-9: “Anilinopyrazole as selective CDK2 inhibitors: design, synthesis, biological evaluation, and X-ray crystallographic analysis.”	ic50	0.0003	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	745528: Inhibition of CDK2/Cyclin A (unknown origin)-mediated phosphorylation of peptide substrate incubated for 15 mins prior to substrate addition measured after 90 mins by P33-radiolabeled assay	ic50	0.0004	uM
4-[[5-amino-1-(3-methylthiophene-2-carbonyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities.”	ic50	0.0004	uM
N-[2-(2-hydroxyethoxy)ethyl]-4-[(7-oxo-6,8-dihydropyrrolo[2,3-g][1,3]benzothiazol-8-yl)methylideneamino]benzenesulfonamide	1796078: Kinase Inhibition SPA Assay from Article 10.1021/jm010117d: “Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis.”	ic50	0.0005	uM
(2S)-N-[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-(3-chlorophenyl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]pyrrolidine-2-carboxamide	262400: Inhibition of CDK2/CyclinA	ic50	0.0006	uM
(2R)-2-[[6-(benzylamino)-9-propan-2-ylpurin-2-yl]amino]butan-1-ol	1868064: Inhibition of CDK2/cyclin A (unknown origin) expressed in baculovirus infected Sf9 cells using histone H1 as substrate incubated for 10 mins in presence of [gamma-32P]ATP by scintillation counter analysis	ic50	0.0007	uM
3-acetyl-7-[[4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-yl]amino]-4-morpholin-4-ylchromen-2-one	1771102: Inhibition of human CDK2/cyclinA using Histone H1 as substrate incubated for 2 hrs by [gamma-33P]-ATP assay	ic50	0.0007	uM
4-[[4-amino-6-(cyclohexylmethoxy)-5-nitrosopyrimidin-2-yl]amino]-N-(2-hydroxyethyl)benzenesulfonamide	1549263: Inhibition of human CDK2/Cyclin A expressed in baculovirus infected Sf9 insect cells	ic50	0.0007	uM
4-[[4-amino-5-(pyridine-3-carbonyl)-1,3-thiazol-2-yl]amino]benzenesulfonamide	745532: Inhibition of human CDK2/Cyclin A2 using PKTPKKAKKL as substrate by P33-radiolabeled assay	ic50	0.0009	uM
N-[[5-[3-(4,6-difluoro-1H-benzimidazol-2-yl)-1H-indazol-4-yl]-4-methyl-3-pyridinyl]methyl]ethanamine	1317306: Inhibition of CDK2/cyclin A (unknown origin)	ic50	0.0010	uM
4-(5-thiophen-3-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine	1477299: Inhibition of CDK2/cyclin A (unknown origin) using histone H1 as substrate after 30 mins in presence of [33P]-gamma-ATP	ic50	0.0010	uM
1-methyl-8-[4-(4-methylpiperazin-1-yl)anilino]-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	1408263: Inhibition of CDK2/Cyclin A2 (unknown origin) using FAM-labeled peptide as substrate after 40 mins	ic50	0.0010	uM
1-methyl-8-[3-(4-methylpiperazin-1-yl)anilino]-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	1799149: Kinase SPA Assay from Article 10.1021/jm9006559: “Identification of N,1,4,4-Tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a Potent, Orally Available Cyclin Dependent Kinase Inhibitor.”	ic50	0.0010	uM
4-[4-methyl-2-(methylamino)-1,3-thiazol-5-yl]-2-(3-nitroanilino)pyrimidine-5-carbonitrile	723734: Inhibition of CDK2/Cyclin A (174 to 432 amino acid residues) (unknown origin) by differential scanning fluorimetry assay	ki	0.0010	uM
ethyl 4-[4-[(3-carbamoyl-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazolin-8-yl)amino]piperidine-1-carbonyl]piperidine-1-carboxylate	460912: Inhibition of CDK2/Cyclin A	ic50	0.0010	uM
1-methyl-8-[[1-(1-methylsulfonylpiperidine-4-carbonyl)piperidin-4-yl]amino]-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	460912: Inhibition of CDK2/Cyclin A	ic50	0.0010	uM
2-[(2S)-1-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol	1317326: Inhibition of recombinant CDK2/cyclin A (unknown origin) expressed in baculovirus infected Sf9 insect cells using biotinylated histone H1 as substrate after 1 hr by gamma32P-ATP based liquid scintillation counting analysis	ic50	0.0010	uM
9-methyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide	527748: Inhibition of CDK2/cyclin A	ic50	0.0010	uM
ethyl 4-[(7-carbamoyl-9-methyl-5,6-dihydropyrrolo[3,2-h]quinazolin-2-yl)amino]piperidine-1-carboxylate	527748: Inhibition of CDK2/cyclin A	ic50	0.0010	uM
9-methyl-2-[3-(4-methylpiperazin-1-yl)anilino]-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide	527748: Inhibition of CDK2/cyclin A	ic50	0.0010	uM
1-(4-methylsulfonylphenyl)-2H-pyrazolo[3,4-e]indazole-3-carboxamide	1795998: Kinase SPA Assay from Article 10.1016/j.bmcl.2005.01.023: “Benzodipyrazoles: a new class of potent CDK2 inhibitors.”	ic50	0.0010	uM
4-[(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)amino]benzonitrile	1796148: Kinase Inhibition SPA Assay from Article 10.1021/jm040063i: “N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as potent and selective inhibitors of glycogen synthase kinase 3 with good cellular efficacy.”	ic50	0.0010	uM
N-(3,4-dichlorophenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine	1796148: Kinase Inhibition SPA Assay from Article 10.1021/jm040063i: “N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as potent and selective inhibitors of glycogen synthase kinase 3 with good cellular efficacy.”	ic50	0.0010	uM
N-(3,5-difluorophenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine	1796148: Kinase Inhibition SPA Assay from Article 10.1021/jm040063i: “N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as potent and selective inhibitors of glycogen synthase kinase 3 with good cellular efficacy.”	ic50	0.0010	uM
4-[[4-[2-(methylamino)-1,3-thiazol-5-yl]pyrimidin-2-yl]amino]benzenesulfonamide	741493: Inhibition of human recombinant His6 tagged CDK2/Cyclin A expressed in Sf21 insect cells after 40 mins by scintillation counting analysis	ki	0.0010	uM
N-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethyl]-N-methyl-4-[(7-oxo-6,8-dihydropyrrolo[2,3-g][1,3]benzothiazol-8-yl)methylideneamino]benzenesulfonamide	1796078: Kinase Inhibition SPA Assay from Article 10.1021/jm010117d: “Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis.”	ic50	0.0010	uM
4-[[4-amino-6-(cyclohexylmethoxy)-5-nitrosopyrimidin-2-yl]amino]benzenesulfonamide	1795792: Kinase Inhibition Assay from Article 10.1016/s0960-894x(03)00651-6: “Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2.”	ic50	0.0011	uM
4-[[4-amino-5-(2-nitrobenzoyl)-1,3-thiazol-2-yl]amino]benzenesulfonamide	745528: Inhibition of CDK2/Cyclin A (unknown origin)-mediated phosphorylation of peptide substrate incubated for 15 mins prior to substrate addition measured after 90 mins by P33-radiolabeled assay	ic50	0.0011	uM
4-[[2-hydroxy-4-(2-methylpropyl)-1H-indol-3-yl]diazenyl]benzenesulfonamide	1796078: Kinase Inhibition SPA Assay from Article 10.1021/jm010117d: “Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis.”	ic50	0.0012	uM
4-[[2-hydroxy-4-(2-methylprop-1-enyl)-1H-indol-3-yl]diazenyl]benzenesulfonamide	1796078: Kinase Inhibition SPA Assay from Article 10.1021/jm010117d: “Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis.”	ic50	0.0015	uM
4-[(2-oxo-3,6-dihydropyrrolo[3,2-f]quinolin-1-yl)methylideneamino]benzenesulfonamide	1796078: Kinase Inhibition SPA Assay from Article 10.1021/jm010117d: “Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis.”	ic50	0.0015	uM
4-[[4-[2-(methylamino)-4-(trifluoromethyl)-1,3-thiazol-5-yl]pyrimidin-2-yl]amino]benzenesulfonamide	741493: Inhibition of human recombinant His6 tagged CDK2/Cyclin A expressed in Sf21 insect cells after 40 mins by scintillation counting analysis	ki	0.0015	uM
4-[(2-oxo-3,6-dihydropyrrolo[3,2-f]quinolin-1-yl)diazenyl]benzenesulfonamide	1326907: Inhibition of human CDK2/cyclinA expressed in Baculovirus infected T.ni cells using Biotin-aminohexyl-Ala-Arg-Arg-Pro-Met-Ser-Pro-Lys-LysLys-Ala-CONH2 as substrate measured after 20 to 30 mins in presence of [gamma-32P]ATP by scintillation counting method	ic50	0.0016	uM
N-[(2,6-dimethoxyphenyl)methyl]-2-hydroxy-3-[(4-sulfamoylphenyl)diazenyl]-1H-indole-5-carboxamide	1796078: Kinase Inhibition SPA Assay from Article 10.1021/jm010117d: “Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis.”	ic50	0.0017	uM
1-[1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl]-4-[5-fluoro-2-(oxan-4-ylamino)pyrimidin-4-yl]pyridin-2-one	1197514: Binding affinity to His-tagged recombinant human full length CDK2/Cyclin A after 60 mins by TR- FRET method	kd	0.0018	uM
4-[[5-(3-methylbutanoyl)-2-oxo-1,3-dihydroindol-3-yl]methylideneamino]benzenesulfonamide	1796078: Kinase Inhibition SPA Assay from Article 10.1021/jm010117d: “Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis.”	ic50	0.0019	uM
(2S,3R)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]propanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxy-3-phenylpropanoic acid	45671: In vitro inhibition of CDK2-cyclin A kinase activity on retinoblastoma protein	ic50	0.0020	uM
N-[6-(3-bromo-4-hydroxyphenyl)-1H-pyrazolo[5,4-b]pyridin-3-yl]cyclopropanecarboxamide	1796182: Kinase Inhibition SPA Assay from Article 10.1016/s0960-894x(03)00646-2: “6-heteroaryl-pyrazolo[3,4-b]pyridines: potent and selective inhibitors of glycogen synthase kinase-3 (GSK-3).”	ic50	0.0020	uM
N-[6-(3-chloro-4-hydroxyphenyl)-1H-pyrazolo[5,4-b]pyridin-3-yl]cyclopropanecarboxamide	1796182: Kinase Inhibition SPA Assay from Article 10.1016/s0960-894x(03)00646-2: “6-heteroaryl-pyrazolo[3,4-b]pyridines: potent and selective inhibitors of glycogen synthase kinase-3 (GSK-3).”	ic50	0.0020	uM
4-[[5-[(4-aminocyclohexyl)amino]-3-bromopyrazolo[1,5-a]pyrimidin-7-yl]amino]-2-chloro-N,N-dimethylbenzenesulfonamide	1796692: CDK Inhibition Assay from Article 10.1016/j.bmcl.2004.12.073: “Structure-guided design of pyrazolo[1,5-a]pyrimidines as inhibitors of human cyclin-dependent kinase 2.”	ic50	0.0020	uM
8-anilino-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	1408263: Inhibition of CDK2/Cyclin A2 (unknown origin) using FAM-labeled peptide as substrate after 40 mins	ic50	0.0020	uM
1-(butylsulfamoyl)-2H-pyrazolo[3,4-e]indazole-3-carboxamide	240909: Inhibition of Cyclin A-cyclin-dependent kinase 2	ic50	0.0020	uM
8-[(1-acetylpiperidin-4-yl)amino]-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	460912: Inhibition of CDK2/Cyclin A	ic50	0.0020	uM
8-(cyclopentylamino)-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	460912: Inhibition of CDK2/Cyclin A	ic50	0.0020	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression, decreases reaction, affects cotreatment	13
Estradiol	affects expression, affects reaction, decreases expression, decreases reaction, increases expression (+1 more)	11
Resveratrol	increases expression, decreases expression	10
Doxorubicin	affects expression, affects localization, decreases expression, affects cotreatment, affects reaction (+4 more)	9
palbociclib	increases expression, affects binding, increases reaction, affects reaction, decreases expression (+1 more)	8
Tretinoin	affects binding, affects reaction, affects cotreatment, decreases reaction, increases expression (+3 more)	7
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance, increases expression	6
Cisplatin	affects reaction, increases reaction, decreases activity, increases activity, decreases expression (+3 more)	6
Benzo(a)pyrene	decreases expression, increases expression	5
Fluorouracil	decreases expression, increases reaction, decreases reaction, affects response to substance, affects expression	5
(+)-JQ1 compound	decreases expression	4
Arsenic Trioxide	affects expression, decreases expression	4
Fulvestrant	decreases reaction, affects cotreatment, decreases expression, affects binding, increases reaction	4
Quercetin	increases expression, decreases expression, affects cotreatment	4
Valproic Acid	decreases expression	4
Cyclosporine	decreases expression	4
Genistein	affects expression, decreases expression, increases expression	4
tert-Butylhydroperoxide	affects expression, decreases expression	4
perfluorooctanoic acid	affects expression, decreases expression	3
Arsenic	affects cotreatment, decreases expression, increases expression, increases abundance	3
Cadmium	increases expression, decreases expression	3
Folic Acid	decreases expression, increases expression, affects cotreatment	3
Hydrogen Peroxide	affects expression, decreases expression	3
Oxygen	affects cotreatment, decreases expression, increases expression	3
Plant Extracts	decreases expression, affects expression, affects reaction	3
Tetrachlorodibenzodioxin	affects expression, decreases expression, increases expression	3
Tetradecanoylphorbol Acetate	increases reaction, decreases expression, increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
Sirolimus	affects cotreatment, decreases expression	3
picrasidine I	decreases expression, increases expression	2

ChEMBL screening assays

738 unique, capped per target: 727 binding, 8 admet, 2 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1040119	Binding	Inhibition of human recombinant CDK2/cyclin A	Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes. — 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
CHEMBL865302	Functional	Inhibition of hyperphosphorylation of pRb by CDK2/cyclin A at 1 uM	3-Amino-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: a new class of CDK2 inhibitors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
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