CCNA1

Summary

CCNA1 (cyclin A1, HGNC:1577) is a protein-coding gene on chromosome 13q13.3, encoding Cyclin-A1 (P78396). May be involved in the control of the cell cycle at the G1/S (start) and G2/M (mitosis) transitions.

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. The cyclin encoded by this gene was shown to be expressed in testis and brain, as well as in several leukemic cell lines, and is thought to primarily function in the control of the germline meiotic cell cycle. This cyclin binds both CDK2 and CDC2 kinases, which give two distinct kinase activities, one appearing in S phase, the other in G2, and thus regulate separate functions in cell cycle. This cyclin was found to bind to important cell cycle regulators, such as Rb family proteins, transcription factor E2F-1, and the p21 family proteins. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8900 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 81 total — 1 pathogenic
• Druggable target: yes — 20 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001413923

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1577
Approved symbol	CCNA1
Name	cyclin A1
Location	13q13.3
Locus type	gene with protein product
Status	Approved
Aliases	CT146
Ensembl gene	ENSG00000133101
Ensembl biotype	protein_coding
OMIM	604036
Entrez	8900

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000255465, ENST00000440264, ENST00000625767, ENST00000630422, ENST00000892819, ENST00000892820, ENST00000892821

RefSeq mRNA: 4 — MANE Select: NM_001413923 NM_001111045, NM_001111046, NM_001111047, NM_001413923

CCDS: CCDS45031

Canonical transcript exons

ENST00000255465 — 9 exons

Exon	Start	End
ENSE00000680650	36439979	36440183
ENSE00000680651	36438644	36438867
ENSE00000680652	36438067	36438191
ENSE00000938553	36437629	36437875
ENSE00001904387	36432495	36432729
ENSE00003329874	36442171	36442304
ENSE00003434101	36441118	36441231
ENSE00003603713	36433033	36433221
ENSE00003766546	36442614	36442870

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 95.38.

FANTOM5 (CAGE): breadth broad, TPM avg 4.0754 / max 242.5244, expressed in 598 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134770	3.5183	505
134769	0.3284	113
134768	0.0697	40
134767	0.0465	3
207004	0.0350	11
134764	0.0313	8
134765	0.0293	6
134766	0.0113	3
207005	0.0056	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	95.38	gold quality
left testis	UBERON:0004533	94.75	gold quality
right testis	UBERON:0004534	94.15	gold quality
ventricular zone	UBERON:0003053	94.12	gold quality
male germ cell	CL:0000015	93.80	gold quality
adult organism	UBERON:0007023	93.63	gold quality
testis	UBERON:0000473	92.09	gold quality
right uterine tube	UBERON:0001302	90.90	gold quality
ganglionic eminence	UBERON:0004023	83.18	gold quality
cortical plate	UBERON:0005343	82.37	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.39	gold quality
middle temporal gyrus	UBERON:0002771	80.79	gold quality
prefrontal cortex	UBERON:0000451	79.22	gold quality
nucleus accumbens	UBERON:0001882	79.11	gold quality
caudate nucleus	UBERON:0001873	77.19	gold quality
right frontal lobe	UBERON:0002810	76.88	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	76.51	gold quality
adenohypophysis	UBERON:0002196	76.01	gold quality
bronchial epithelial cell	CL:0002328	75.97	gold quality
Brodmann (1909) area 9	UBERON:0013540	75.75	gold quality
pituitary gland	UBERON:0000007	75.56	gold quality
neocortex	UBERON:0001950	75.17	gold quality
frontal cortex	UBERON:0001870	74.96	gold quality
hypothalamus	UBERON:0001898	74.61	gold quality
cingulate cortex	UBERON:0003027	74.58	gold quality
anterior cingulate cortex	UBERON:0009835	74.30	gold quality
Brodmann (1909) area 23	UBERON:0013554	74.08	gold quality
cerebral cortex	UBERON:0000956	73.98	gold quality
endocervix	UBERON:0000458	73.77	gold quality
telencephalon	UBERON:0001893	73.44	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-36552	yes	744.06
E-ANND-3	no	3.23

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
WT1	Repression

Upstream regulators (CollecTRI, top): ATF1, ATF2, ATF3, CREB1, CREM, CXXC1, KDM4B, LEF1, MYB, MYBL2, NR2C2, PITX2, RARA, SIX1, SP1, SP3, TCF3, TFCP2, TP53, XBP1

miRNA regulators (miRDB)

21 targeting CCNA1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-606	98.72	67.34	960
HSA-MIR-640	98.44	66.93	644
HSA-MIR-4529-3P	96.40	66.46	582
HSA-MIR-6514-5P	95.07	66.02	655

Literature-anchored findings (GeneRIF, showing 40)

• the level of cyclin A1 mRNA expression predicts meiotic disorders during spermatogenesis (PMID:12121569)
• CCNA1 had successive increases in its promoter activity during spermatgogensis in transgenic mice. (PMID:12579332)
• 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)
• Cyclin A1 methylation was inversely related to p53 mutational status in primary tumors, and forced expression of cyclin A1 resulted in robust induction of wild-type p53 in HNSCC cell lines. (PMID:15342377)
• These findings establish a novel function for cyclin A1 and CDK2 in DNA double strand break repair following radiation damage. (PMID:15456866)
• these analyses demonstrate that cyclin A1 contributes to G1 to S cell cycle progression in somatic cells. (PMID:15829981)
• cyclin A1 mediates VEGF expression in cooperation with Rb- and androgen-dependent pathways in prostate cancer (PMID:16007189)
• Significant tumour specific methylation of cyclin A1 promoter seen in oral sqmaous cell carcinoma (PMID:16449996)
• The data implicate cyclin A1 as a downstream player in p53-dependent apoptosis and G2 arrest. (PMID:16799873)
• Mip/LIN-9 is required for the expression of B-Myb, and both proteins collaborate in the control of the cell cycle progression via the regulation of S phase and cyclin A, cyclin B, and CDK1 (PMID:17098733)
• these analyses demonstrate that cyclin A1 exerts antiapoptotic functions by interacting with retinoblastoma and Ku proteins in leukemia cells. (PMID:17455244)
• Over expression of H179Y-mutant p53 promoted G1 to S phase transition with enlarged cell size and increased cyclin A1 and Cdk4 expression in HELF cells. (PMID:17530187)
• G2 phase cyclin A/cdk2 controls the timing of entry into mitosis by controlling the subsequent activation of cyclin B/cdk1, but also has an unexpected role in coordinating the activation of cyclin B/cdk1 at the centrosome and in the nucleus (PMID:18372919)
• Cyclin A1 contributes to prostate cancer invasion by modulating the expression of MMPs and VEGF and by interacting with AR (androgen receptor). (PMID:18612129)
• The CCNA1, CCNB1, CCNB2, PRM1, and PRM2 messenger RNA transcript ratios were significantly decreased in patients with spermatogenic disorders. Transcript ratios in patients with successful sperm retrieval were higher than with failed sperm retrieval. (PMID:18692784)
• Results suggest that cyclin A1 protein is stabilized via post-transcriptional modification in response to apoptosis induced by staurosporine or TNFalpha. (PMID:18787932)
• Cyclin A1- and cyclin A2-containing CDK complexes were compared in vitro by determining kinetic constants and by examining the complexes for their ability to phosphorylate pRb and p53. (PMID:19056339)
• mRNA expression of cyclin A1 in myelodysplastic syndrome patients is higher than in normal controls. (PMID:19379570)
• Study shows that transcription corepressor CtBP2 directly binds acinus, which is regulated by nerve growth factor (NGF), inhibiting its stimulatory effect on cyclin A1, but not cyclin A2, expression in leukemia. (PMID:19668232)
• Methylation of CCNA1 in cervical scrapings is strongly associated with high-grade cervical intraepithelial neoplasia and cervical cancer. (PMID:19843677)
• Four point mutations, c.321T>C, IVS3 +32G>C, IVS5+38A>G and c.1158G>A, are not associated with spermatogenesis impairment. (PMID:19886767)
• An increase in cyclin A1 expression was the only differentially expressed cell cycle regulatory gene found. Greater cyclin A protein levels were consistently observed in cells with active IRE1alpha and were dependent on XBP-1. (PMID:20013084)
• These results indicate that HIV-1 integrase is required during uncoating for maintaining CypA-capsid protein interaction, which promotes optimal stability of the viral core. (PMID:20219923)
• revealed that KDM8 occupies the coding region of cyclin A1 and directly regulates transcription. (PMID:20457893)
• The integrated form of HPV might lead to CCNA1 promoter methylation in cervical cancer by some mechanisms. (PMID:21412159)
• CCNA1 methylation may play a crucial role in HPV16-induced carcinogenesis of HNSCC independently of p53 (PMID:21563216)
• anti-oncogenic role of miR-372 may be through control of cell growth and cell cycle progression by down-regulating the cell cycle genes CDK2 and cyclin A1 (PMID:21646351)
• Oxidized low density lipoprotein induces cyclin A synthesis in a process involving ERK, JNK and NFkappaB (PMID:21764057)
• Increased cyclin A1 in human bladder cancer cells may be regulated by activity of the USP2a deubiquitinase. (PMID:22370483)
• Cyclin A1 as overexpressed in induced lpuripotent stem cells cells compared to embryonic stem cells, suggesting that during reprogramming, cyclin A1 protein expression levels are not set correctly. (PMID:22500553)
• Cyclin-A1 is the first prototypic leukemia-testis-antigen to be expressed in acute myeloid leukemia leukemic stem cells. (PMID:22529286)
• Cyclin A1 is an important cell cycle regulator with age-related increased expression in tonsils of children. HPV16 induces overexpression of Cyclin A1 in HNSCC despite promoter methylation. (PMID:22712549)
• Nuclear FoxO3a promotes cell cycle progression by transcriptional upregulation of cyclin A1, promoting proliferation of human anaplastic thyroid carcinoma cells. (PMID:22718346)
• These findings indicate the possible involvement of cyclins A and E in the pathogenesis of malignant melanoma. (PMID:22763964)
• The organization of actin and cytokeratin cytoskeleton and the expression of TCTP, p53,cyclin A, RhoA and actin in HIO180 non-transformed ovarian epithelial cells, and OVCAR3 and SKOV3 ovarian epithelial cancer cells, was studied. (PMID:23042265)
• Data indicate that induction of cyclin A1 overexpression in breast cancer cell line MCF-7 results in an enhanced invasiveness and a concomitant increase in vascular endothelial growth factor (VEGF) expression. (PMID:23991063)
• Promoter reporter assays with a series of deletion constructs determined that the DNA element from -102 to -96 bp of the cyclin A1 promoter is responsible for PITX2-induced gene expression. (PMID:24002705)
• Overexpression of cyclin A1 in FSHD indicates cell cycle dysregulation in FSHD and might contribute to clinical symptoms of this disease (PMID:24019929)
• presents CCNA1 and TIMP3 hypermethylation as a helpful tool to identify HNSCC subjects at risk of developing second primary carcinomas (PMID:24359512)
• Cyclin A1 immunoexpression is of potential utility in predicting disease progression in patients with pT1 urothelial carcinomas of the bladder (PMID:25039670)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccna1	ENSDARG00000043236
mus_musculus	Ccna1	ENSMUSG00000027793
rattus_norvegicus	Ccna1	ENSRNOG00000014052
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), CCNB1 (ENSG00000134057), CCNJL (ENSG00000135083), CCNG2 (ENSG00000138764), CCNA2 (ENSG00000145386), CCNB3 (ENSG00000147082), CCNO (ENSG00000152669), CCNB2 (ENSG00000157456), CCNF (ENSG00000162063), CCNE2 (ENSG00000175305), CCNI2 (ENSG00000205089)

Protein

Protein identifiers

Cyclin-A1 — P78396 (reviewed: P78396)

All UniProt accessions (1): P78396

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the control of the cell cycle at the G1/S (start) and G2/M (mitosis) transitions. May primarily function in the control of the germline meiotic cell cycle and additionally in the control of mitotic cell cycle in some somatic cells.

Subunit / interactions. Interacts with the CDK2 and the CDC2 protein kinases to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Does not bind CDK4 and CDK5 (in vitro). The cyclin A1-CDK2 complex interacts with transcription factor E2F-1 and RB proteins. Found in a complex with CDK2, CABLES1 and CCNE1. Interacts with INCA1. Interacts with KLHDC9.

Subcellular location. Nucleus.

Tissue specificity. Very high levels in testis and very low levels in brain. Also found in myeloid leukemia cell lines.

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.

Isoforms (3)

UniProt ID	Names	Canonical?
P78396-1	1	yes
P78396-2	2
P78396-3	3

RefSeq proteins (4): NP_001104515, NP_001104516, NP_001104517, NP_001400852* (*=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
IPR048258	Cyclins_cyclin-box	Conserved_site

Pfam: PF00134, PF02984, PF16500

UniProt features (4 total): splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78396-F1	68.65	0.54

Function

Pathways and Gene Ontology

Reactome pathways

61 pathways

ID	Pathway
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-69205	G1/S-Specific Transcription
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: 0 (showing top):

GO Biological Process (4): G1/S transition of mitotic cell cycle (GO:0000082), male meiosis I (GO:0007141), spermatogenesis (GO:0007283), cell division (GO:0051301)

GO Molecular Function (2): cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytosol (GO:0005829), microtubule cytoskeleton (GO:0015630), cyclin A1-CDK1 complex (GO:0097121), cyclin A1-CDK2 complex (GO:0097123), 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
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
G1/S Transition	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cyclin-dependent protein kinase holoenzyme complex	3
male gamete generation	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
meiosis I	1
male meiotic nuclear division	1
meiotic cell cycle	1
developmental process involved in reproduction	1
cellular process	1
cyclin-dependent protein serine/threonine kinase activity	1
cyclin-dependent protein kinase regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
cytoplasm	1
cytoskeleton	1

Protein interactions and networks

STRING

3720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCNA1	CDK2	P24941	999
CCNA1	CDK1	P06493	998
CCNA1	CDKN1B	P46527	997
CCNA1	SKP2	Q13309	997
CCNA1	CDKN1A	P38936	996
CCNA1	CDK6	Q00534	987
CCNA1	E2F1	Q01094	985
CCNA1	CDK4	P11802	979
CCNA1	SKP1	P34991	967
CCNA1	CCNL2	Q96S94	950
CCNA1	TP53	P04637	949
CCNA1	CDC25B	P30305	942
CCNA1	RB1	P06400	908
CCNA1	CDC6	Q99741	907
CCNA1	CDKN1C	P49918	882

IntAct

67 interactions, top by confidence:

A	B	Type	Score
CDKN1A	CDK2	psi-mi:“MI:0914”(association)	0.980
CDK2	CCNB2	psi-mi:“MI:0914”(association)	0.860
CDKN1A	CCNA1	psi-mi:“MI:2364”(proximity)	0.840
CDKN1A	CCNA1	psi-mi:“MI:0915”(physical association)	0.840
CDKN1A	CCNA1	psi-mi:“MI:0407”(direct interaction)	0.840
CCNA1	CDKN1A	psi-mi:“MI:2364”(proximity)	0.840
CDKN1B	CCNA1	psi-mi:“MI:0915”(physical association)	0.780
CDKN1B	CCNA1	psi-mi:“MI:2364”(proximity)	0.780
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
ORC1	CCNA2	psi-mi:“MI:0914”(association)	0.730
CCNA1	PTK2	psi-mi:“MI:2364”(proximity)	0.540
CDT1	CDK1	psi-mi:“MI:0914”(association)	0.530
CCNA1	CDK2	psi-mi:“MI:2364”(proximity)	0.480
MCM6	CCNA1	psi-mi:“MI:0407”(direct interaction)	0.440
MCM4	CCNA1	psi-mi:“MI:0407”(direct interaction)	0.440
	CCNA1	psi-mi:“MI:0915”(physical association)	0.400
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
COPS6	DDX3X	psi-mi:“MI:0914”(association)	0.350
ORC2	CCNA2	psi-mi:“MI:0914”(association)	0.350
CDKN1B	YKT6	psi-mi:“MI:0914”(association)	0.350
CCNA2	TBC1D4	psi-mi:“MI:0914”(association)	0.350

BioGRID (162): CCNA1 (Reconstituted Complex), CCNA1 (Affinity Capture-MS), CCNA1 (Co-localization), CCNA1 (Co-localization), CCNA1 (Co-localization), CCNA1 (Reconstituted Complex), CCNA1 (Biochemical Activity), CCNA1 (Affinity Capture-MS), CCNA1 (Affinity Capture-MS), CCAR2 (Affinity Capture-MS), TGFB1I1 (Affinity Capture-MS), VPS18 (Affinity Capture-MS), MCC (Affinity Capture-MS), GPS2 (Two-hybrid), XRCC6 (Two-hybrid)

ESM2 similar proteins: A0MEB5, A2YH60, O14332, O43008, O94612, P04962, P14785, P18606, P20248, P24861, P24865, P24868, P24869, P24871, P25009, P25010, P30183, P30274, P30283, P32943, P34638, P36630, P37881, P46277, P46278, P47827, P51943, P51986, P78396, Q01J96, Q06374, Q0D9C7, Q0DJR9, Q10653, Q10654, Q147G5, Q2QQ96, Q38819, Q39068, Q39070

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

8 interactions.

A	Effect	B	Mechanism
RARA	“down-regulates quantity by repression”	CCNA1	“transcriptional regulation”
PML-RARalpha	“up-regulates quantity by expression”	CCNA1	“transcriptional regulation”
CCNA1	up-regulates	Proliferation
CCNA1	“down-regulates quantity by repression”	WT1	“transcriptional regulation”
PML-RARalpha	“up-regulates activity”	CCNA1
SMARCB1	down-regulates	CCNA1
CCNA1	up-regulates	Cell_growth
CCNA1	up-regulates	G1/S_transition

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
TP53 Regulates Transcription of Cell Cycle Genes	5	55.5×	7e-07
Activation of the pre-replicative complex	8	53.3×	1e-10
G1/S Transition	10	47.6×	1e-12
Activation of ATR in response to replication stress	7	42.9×	8e-09
Switching of origins to a post-replicative state	7	42.9×	8e-09
Synthesis of DNA	7	42.9×	8e-09
Orc1 removal from chromatin	11	40.1×	9e-13
DNA Replication Pre-Initiation	6	38.8×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
regulation of DNA-templated DNA replication initiation	5	94.0×	4e-07
DNA replication initiation	5	55.7×	3e-06
positive regulation of DNA replication	5	51.9×	4e-06
G1/S transition of mitotic cell cycle	7	25.1×	2e-06
DNA replication	6	17.7×	8e-05
Wnt signaling pathway	5	8.9×	7e-03
DNA repair	6	6.8×	7e-03
cell division	7	5.8×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	58
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
149761	GRCh38/hg38 13q12.3-14.2(chr13:31018160-48491204)x1	Pathogenic

SpliceAI

1042 predictions. Top by Δscore:

Variant	Effect	Δscore
13:36438065:A:AG	acceptor_gain	1.0000
13:36438066:G:GA	acceptor_gain	1.0000
13:36438192:G:GG	donor_gain	1.0000
13:36438638:A:AG	acceptor_gain	1.0000
13:36438639:A:G	acceptor_gain	1.0000
13:36438642:A:AG	acceptor_gain	1.0000
13:36438643:G:GG	acceptor_gain	1.0000
13:36438643:GAT:G	acceptor_gain	1.0000
13:36438643:GATA:G	acceptor_gain	1.0000
13:36438643:GATAA:G	acceptor_gain	1.0000
13:36438863:GCTTC:G	donor_gain	1.0000
13:36438868:G:GG	donor_gain	1.0000
13:36439974:CCCA:C	acceptor_loss	1.0000
13:36439975:CCAG:C	acceptor_loss	1.0000
13:36439976:CA:C	acceptor_loss	1.0000
13:36439977:A:AG	acceptor_gain	1.0000
13:36439977:AG:A	acceptor_gain	1.0000
13:36439977:AGGA:A	acceptor_loss	1.0000
13:36439978:G:A	acceptor_loss	1.0000
13:36439978:G:GG	acceptor_gain	1.0000
13:36439978:GG:G	acceptor_gain	1.0000
13:36439978:GGA:G	acceptor_gain	1.0000
13:36439978:GGAA:G	acceptor_gain	1.0000
13:36440182:AGG:A	donor_loss	1.0000
13:36440183:GGTG:G	donor_loss	1.0000
13:36440184:GTGT:G	donor_loss	1.0000
13:36441109:T:A	acceptor_gain	1.0000
13:36441111:T:TA	acceptor_gain	1.0000
13:36441113:CTTA:C	acceptor_loss	1.0000
13:36441115:TA:T	acceptor_loss	1.0000

AlphaMissense

3011 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:36438722:T:A	W250R	0.998
13:36438722:T:C	W250R	0.998
13:36438724:G:C	W250C	0.998
13:36438724:G:T	W250C	0.998
13:36438831:T:C	L286P	0.996
13:36438864:C:A	A297D	0.996
13:36439982:A:C	K299N	0.996
13:36439982:A:T	K299N	0.996
13:36440056:T:C	L324P	0.996
13:36440094:T:C	F337L	0.996
13:36440096:T:A	F337L	0.996
13:36440096:T:G	F337L	0.996
13:36438726:T:C	L251P	0.995
13:36438801:T:C	L276P	0.995
13:36439981:A:T	K299I	0.995
13:36440124:T:C	F347L	0.994
13:36440126:T:A	F347L	0.994
13:36440126:T:G	F347L	0.994
13:36438704:C:A	R244S	0.993
13:36438797:T:C	F275L	0.993
13:36438799:C:A	F275L	0.993
13:36438799:C:G	F275L	0.993
13:36438837:T:C	L288P	0.993
13:36438843:G:A	G290E	0.993
13:36441182:C:A	A388D	0.993
13:36438705:G:C	R244P	0.992
13:36438703:G:A	M243I	0.991
13:36438703:G:C	M243I	0.991
13:36438703:G:T	M243I	0.991
13:36438714:T:C	L247P	0.991

dbSNP variants (sampled 300 via entrez): RS1000039439 (13:36436998 T>A), RS1000557771 (13:36436774 C>T), RS1000618259 (13:36433309 T>C,G), RS1000820410 (13:36431378 C>A,T), RS1000968174 (13:36437265 A>G), RS1001148613 (13:36436824 A>G), RS1001748655 (13:36435441 C>G), RS1001800500 (13:36442330 T>C), RS1001815453 (13:36430511 G>A), RS1001824332 (13:36429999 G>C), RS1002775610 (13:36441370 G>A,C), RS1002966269 (13:36434259 A>G), RS1003158019 (13:36434056 T>C), RS1003740402 (13:36432508 A>G), RS1003895988 (13:36430376 T>A)

Disease associations

OMIM: gene MIM:604036 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002928_22	Nickel levels	5.000000e-06
GCST008399_20	Cocaine dependence	2.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2094128 (PROTEIN COMPLEX), CHEMBL3038470 (PROTEIN COMPLEX), CHEMBL3885548 (PROTEIN COMPLEX), CHEMBL4296066 (PROTEIN COMPLEX), CHEMBL5483182 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

20 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 102,224 (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
CHEMBL576982	QUIZARTINIB	4	4,432
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
CHEMBL5199065	ISTISOCICLIB	2	21
CHEMBL1230607	PHA-793887	1	299
CHEMBL269538	HARMINE	1	4,346
CHEMBL4439321	ATUVECICLIB	1	129
CHEMBL488436	AZD-5438	1	1,333
CHEMBL296468	BMS-387032	1	2,075

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

Binding affinities (BindingDB)

59 measured of 59 human assays (59 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[[5-(piperazine-1-carbonyl)-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	61 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-(4-methylpiperazine-1-carbonyl)-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclopentane]-10-one	IC50	85 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-(3,3-dimethylbutyl)piperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclopentane]-10-one	IC50	87.3 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-(4-cyclobutylpiperazine-1-carbonyl)-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	108 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-(4-cyclobutylpiperazin-1-yl)-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	190 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-(cyclopropylmethyl)piperazine-1-carbonyl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclopentane]-10-one	IC50	203 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-(3-propan-2-ylpiperazin-1-yl)-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	204 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-(4-propan-2-ylpiperazine-1-carbonyl)-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	239 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-(cyclopropylmethyl)piperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	265 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-[(2R)-2-hydroxypropyl]piperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	342 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-(cyclopropylmethyl)-3,3-dimethylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	377 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-(3,3-dimethylbutyl)-3,3-dimethylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclopentane]-10-one	IC50	457 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-(4-cyclopropyl-3,3-dimethylpiperazin-1-yl)-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	502 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-(2-hydroxy-2-methylpropyl)-3-methylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	539 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-(cyclopropylmethyl)-3,5-dimethylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	570 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[6-(4-propan-2-ylpiperazin-1-yl)pyridazin-3-yl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	596 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[(3R,5S)-4-[(2R)-2-hydroxypropyl]-3,5-dimethylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	597 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[(3S)-4-[(2S)-2-hydroxypropyl]-3-methylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	616 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-(3,3-dimethylbutyl)-3-methylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	646 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[(3R,5S)-4-[(2S)-2-hydroxypropyl]-3,5-dimethylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	647 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-[3-(diethylamino)pyrrolidin-1-yl]piperidin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	693 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-(3-methylpyrrolidin-1-yl)piperidin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	738 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-(diethylamino)piperidin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	755 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[(3S)-4-[(2R)-2-hydroxypropyl]-3-methylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclopentane]-10-one	IC50	789 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-(4-morpholin-4-ylpiperidin-1-yl)-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	857 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[(3S)-3-methylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	915 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-(2-hydroxy-2-methylpropyl)piperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclopentane]-10-one	IC50	943 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-(2-ethoxyethyl)piperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclopentane]-10-one	IC50	990 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[(3S,5R)-3,5-dimethylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	1010 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-(cyclopropylmethyl)-3-methylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclopentane]-10-one	IC50	1010 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[(4-propan-2-ylpiperazin-1-yl)methyl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	1110 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-(3,3-dimethylpiperazin-1-yl)-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	1130 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[(3S)-3,4-dimethylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	1360 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-(2-methylbutyl)piperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclopentane]-10-one	IC50	1370 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[6-[4-(dimethylamino)piperidin-1-yl]pyridazin-3-yl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	1390 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[(3S,5R)-4-ethyl-3,5-dimethylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	1400 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[(3S)-4-(3,3-dimethylbutyl)-3-methylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	1410 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[(3R)-3-methyl-4-propan-2-ylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	1490 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-(3,3,4-trimethylpiperazin-1-yl)-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	1500 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-(4-propan-2-ylpiperazin-1-yl)-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	1510 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[(3R)-3,4-dimethylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	1560 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
Trilaciclib	IC50	1670 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-[4-(trifluoromethyl)piperidin-1-yl]piperidin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	1840 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[(6-morpholin-4-ylpyridazin-3-yl)amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclopentane]-10-one	IC50	1880 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[(3S)-4-(cyclopropylmethyl)-3-methylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	1890 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[(3R)-3-methylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	2130 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[3-(diethylamino)pyrrolidin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	2570 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[4-(3,3-dimethylbutyl)-3-methylpiperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclopentane]-10-one	IC50	2640 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[[5-[(3R,5S)-3,5-dimethyl-4-(2-methylbutyl)piperazin-1-yl]-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclopentane]-10-one	IC50	2830 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation
4-[(5-piperazin-1-yl-2-pyridinyl)amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	IC50	3030 nM	US-9527857: HSPC-sparing treatments for RB-positive abnormal cellular proliferation

ChEMBL bioactivities

1134 potent at pChembl≥5 of 1282 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	Ki	0.2	nM	CHEMBL2312187
9.52	IC50	0.3	nM	CHEMBL360520
9.52	IC50	0.3	nM	CHEMBL363607
9.40	IC50	0.4	nM	CHEMBL363130
9.30	IC50	0.5	nM	STAUROSPORINE
9.30	IC50	0.5	nM	CHEMBL261720
9.22	IC50	0.6	nM	CHEMBL382690
9.12	IC50	0.761	nM	STAUROSPORINE
9.00	Ki	1	nM	CHEMBL2312182
9.00	Ki	1	nM	CHEMBL2348844
9.00	IC50	1	nM	CHEMBL361595
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
8.97	IC50	1.08	nM	CHEMBL4080236
8.85	IC50	1.4	nM	STAUROSPORINE
8.82	Ki	1.5	nM	CHEMBL2348843
8.82	IC50	1.51	nM	STAUROSPORINE
8.80	IC50	1.59	nM	CHEMBL4093906
8.76	IC50	1.74	nM	CHEMBL4073053
8.75	IC50	1.77	nM	STAUROSPORINE
8.74	IC50	1.8	nM	CHEMBL2377825
8.73	IC50	1.87	nM	CHEMBL4086149
8.72	IC50	1.9	nM	CHEMBL4093755
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
8.70	IC50	2	nM	CHEMBL192602
8.70	IC50	2	nM	CHEMBL429171
8.70	IC50	2	nM	CHEMBL597754
8.70	IC50	2	nM	CHEMBL599224
8.70	IC50	2	nM	CHEMBL599607
8.70	IC50	2	nM	CHEMBL559845
8.70	IC50	2	nM	CHEMBL1094401
8.70	IC50	2	nM	CHEMBL1099105
8.70	IC50	2	nM	CHEMBL1099106
8.70	IC50	2	nM	CHEMBL1270419
8.70	IC50	2	nM	CHEMBL1270920
8.70	IC50	2	nM	CHEMBL1271329
8.69	IC50	2.05	nM	CHEMBL4076277
8.68	IC50	2.08	nM	CHEMBL4104057
8.61	IC50	2.47	nM	CHEMBL4077071
8.52	Ki	3	nM	CHEMBL2312190
8.52	Ki	3	nM	CHEMBL2312186

PubChem BioAssay actives

1064 with measured affinity, of 2362 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
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
1-(4-sulfamoylphenyl)-2H-pyrazolo[3,4-e]indazole-3-carboxamide	240909: Inhibition of Cyclin A-cyclin-dependent kinase 2	ic50	0.0003	uM
4-[[5-amino-1-(3-methylthiophene-2-carbonyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	241015: Inhibition of Cyclin-dependent kinase 2-cyclin A	ic50	0.0004	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	745527: Inhibition of CDK2/Cyclin A1 (unknown origin)-mediated phosphorylation of peptide substrate incubated for 15 mins prior to substrate addition measured after 90 mins by P33-radiolabeled assay	ic50	0.0005	uM
5-amino-N-(2,6-difluorophenyl)-3-(4-sulfamoylanilino)-1,2,4-triazole-1-carbothioamide	241227: Inhibition of Cyclin-dependent kinase 2-cyclin A	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
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
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	240909: Inhibition of Cyclin A-cyclin-dependent kinase 2	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
4-[(5-methylthieno[2,3-d]pyrimidin-4-yl)amino]-N-[4-(morpholin-4-ylmethyl)phenyl]-1H-pyrazole-5-carboxamide	1489802: Inhibition of human CDK2/Cyclin A1 using histone H1 as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition measure after 120 mins by filter binding method	ic50	0.0011	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
N-[4-(diethylaminomethyl)phenyl]-4-(thieno[2,3-d]pyrimidin-4-ylamino)-1H-pyrazole-5-carboxamide	1489802: Inhibition of human CDK2/Cyclin A1 using histone H1 as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition measure after 120 mins by filter binding method	ic50	0.0016	uM
N-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-4-[(6-methylthieno[2,3-d]pyrimidin-4-yl)amino]-1H-pyrazole-5-carboxamide	1489802: Inhibition of human CDK2/Cyclin A1 using histone H1 as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition measure after 120 mins by filter binding method	ic50	0.0017	uM
4-[[4-amino-5-(2-nitrobenzoyl)-1,3-thiazol-2-yl]amino]benzenesulfonamide	745527: Inhibition of CDK2/Cyclin A1 (unknown origin)-mediated phosphorylation of peptide substrate incubated for 15 mins prior to substrate addition measured after 90 mins by P33-radiolabeled assay	ic50	0.0018	uM
4-[(6-ethylthieno[2,3-d]pyrimidin-4-yl)amino]-N-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrazole-5-carboxamide	1489802: Inhibition of human CDK2/Cyclin A1 using histone H1 as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition measure after 120 mins by filter binding method	ic50	0.0019	uM
4-[(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)amino]-N-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrazole-5-carboxamide	1489802: Inhibition of human CDK2/Cyclin A1 using histone H1 as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition measure after 120 mins by filter binding method	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
8-anilino-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480530: Inhibition of CDK2/Cyclin A assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	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
8-anilino-4,5-dihydro-2H-pyrazolo[4,3-h]quinazoline-3-carboxamide	480530: Inhibition of CDK2/Cyclin A assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0020	uM
N,1-dimethyl-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	0.0020	uM
8-(3-acetylanilino)-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480530: Inhibition of CDK2/Cyclin A assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0020	uM
8-(4-acetylanilino)-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480530: Inhibition of CDK2/Cyclin A assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0020	uM
9-methyl-2-[4-(4-methylpiperazin-1-yl)anilino]-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide	527748: Inhibition of CDK2/cyclin A	ic50	0.0020	uM
N,9-dimethyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide	527748: Inhibition of CDK2/cyclin A	ic50	0.0020	uM
2-[(1-acetylpiperidin-4-yl)amino]-9-methyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide	527748: Inhibition of CDK2/cyclin A	ic50	0.0020	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	241015: Inhibition of Cyclin-dependent kinase 2-cyclin A	ic50	0.0020	uM
(2S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-[4-(3-oxo-1H-isoindol-2-yl)phenyl]propanamide	241238: Inhibition of cyclin dependent kinase 2-cyclin A	ic50	0.0020	uM
(2S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-[4-(2-oxoimidazolidin-1-yl)phenyl]propanamide	241238: Inhibition of cyclin dependent kinase 2-cyclin A	ic50	0.0020	uM
1-[4-(butylsulfamoyl)phenyl]-2H-pyrazolo[3,4-e]indazole-3-carboxamide	240909: Inhibition of Cyclin A-cyclin-dependent kinase 2	ic50	0.0020	uM
1-(2,2,2-trifluoroethyl)-2H-pyrazolo[3,4-e]indazole-3-carboxamide	240909: Inhibition of Cyclin A-cyclin-dependent kinase 2	ic50	0.0020	uM
3-[[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	0.0020	uM
3-[[4-[4-cyclopropyl-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	0.0020	uM
N-[4-[(cyclopropylamino)methyl]phenyl]-4-(thieno[2,3-d]pyrimidin-4-ylamino)-1H-pyrazole-5-carboxamide	1489802: Inhibition of human CDK2/Cyclin A1 using histone H1 as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition measure after 120 mins by filter binding method	ic50	0.0021	uM
N-[4-(piperazin-1-ylmethyl)phenyl]-4-(thieno[2,3-d]pyrimidin-4-ylamino)-1H-pyrazole-5-carboxamide	1489802: Inhibition of human CDK2/Cyclin A1 using histone H1 as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition measure after 120 mins by filter binding method	ic50	0.0021	uM
N-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-4-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-1H-pyrazole-5-carboxamide	1489802: Inhibition of human CDK2/Cyclin A1 using histone H1 as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition measure after 120 mins by filter binding method	ic50	0.0025	uM
N-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]-4-(thieno[2,3-d]pyrimidin-4-ylamino)-1H-pyrazole-5-carboxamide	1489802: Inhibition of human CDK2/Cyclin A1 using histone H1 as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition measure after 120 mins by filter binding method	ic50	0.0030	uM
4-(4-propoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine	315300: Inhibition of human recombinant CDK2/cyclin A expressed in insect cells	ic50	0.0030	uM
1-methyl-8-(2-methylanilino)-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480530: Inhibition of CDK2/Cyclin A assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0030	uM
8-anilino-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxylic acid	480530: Inhibition of CDK2/Cyclin A assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0030	uM
2-(4-hydroxyanilino)-4-[4-methyl-2-(methylamino)-1,3-thiazol-5-yl]pyrimidine-5-carbonitrile	723734: Inhibition of CDK2/Cyclin A (174 to 432 amino acid residues) (unknown origin) by differential scanning fluorimetry assay	ki	0.0030	uM
4-[4-methyl-2-(methylamino)-1,3-thiazol-5-yl]-2-(4-morpholin-4-ylsulfonylanilino)pyrimidine-5-carbonitrile	723734: Inhibition of CDK2/Cyclin A (174 to 432 amino acid residues) (unknown origin) by differential scanning fluorimetry assay	ki	0.0030	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression, decreases expression, decreases reaction	10
Valproic Acid	increases methylation, affects expression, decreases expression, increases expression	8
sodium arsenite	decreases expression, decreases reaction, increases expression	4
Cadmium Chloride	affects cotreatment, decreases expression, increases abundance, increases expression, affects expression (+1 more)	4
bisphenol A	increases expression, affects cotreatment, increases methylation	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation, affects expression	3
Cadmium	increases abundance, increases expression	3
Nickel	affects cotreatment, increases expression	3
trichostatin A	increases reaction, decreases expression, increases expression, affects binding, decreases reaction	2
Decitabine	affects expression, affects methylation	2
Arsenic Trioxide	increases expression, decreases expression, decreases reaction	2
Fulvestrant	affects cotreatment, increases methylation, affects expression, affects response to substance	2
Progesterone	decreases expression, increases expression, affects cotreatment	2
Tretinoin	increases response to substance, decreases expression, increases expression	2
Lithium Chloride	decreases expression, increases expression	2
Okadaic Acid	affects expression, increases expression	2
peracetylated N-azidoacetylmannosamine	decreases expression	1
triptolide	decreases expression	1
taxifolin	decreases expression	1
quinone	decreases expression, decreases reaction	1
bufotalin	decreases expression	1
methylmercuric chloride	increases expression	1
propionaldehyde	increases methylation	1
propylparaben	increases expression	1
nonanal	increases methylation	1
n-hexanal	increases methylation	1
2-methyl-4-isothiazolin-3-one	increases expression	1
diethyl maleate	decreases expression	1
methylparaben	increases expression	1
o,p’-DDT	increases expression	1

ChEMBL screening assays

336 unique, capped per target: 333 binding, 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

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_ZF78	CLC18	Cancer cell line	Male
CVCL_ZG13	CLC9	Cancer cell line	Male

Clinical trials (associated diseases)

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