CCNE1

Summary

CCNE1 (cyclin E1, HGNC:1589) is a protein-coding gene on chromosome 19q12, encoding G1/S-specific cyclin-E1 (P24864). Essential for the control of the cell cycle at the G1/S (start) transition. In precision oncology, CCNE1 Underexpression confers sensitivity to Fulvestrant + Palbociclib in Breast Cancer (CIViC Level B); 11 further curated variant–drug associations are listed below.

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. This cyclin forms a complex with and functions as a regulatory subunit of CDK2, whose activity is required for cell cycle G1/S transition. This protein accumulates at the G1-S phase boundary and is degraded as cells progress through S phase. Overexpression of this gene has been observed in many tumors, which results in chromosome instability, and thus may contribute to tumorigenesis. This protein was found to associate with, and be involved in, the phosphorylation of NPAT protein (nuclear protein mapped to the ATM locus), which participates in cell-cycle regulated histone gene expression and plays a critical role in promoting cell-cycle progression in the absence of pRB.

Source: NCBI Gene 898 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 59 total
• Druggable target: yes — 38 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 12 curated variant–drug associations
• MANE Select transcript: NM_001238

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1589
Approved symbol	CCNE1
Name	cyclin E1
Location	19q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000105173
Ensembl biotype	protein_coding
OMIM	123837
Entrez	898

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 retained_intron

ENST00000262643, ENST00000357943, ENST00000444983, ENST00000574121, ENST00000575243, ENST00000576532, ENST00000586912, ENST00000855968, ENST00000937503, ENST00000937504, ENST00000937505, ENST00000937506, ENST00000937507, ENST00000937508

RefSeq mRNA: 4 — MANE Select: NM_001238 NM_001238, NM_001322259, NM_001322261, NM_001322262

CCDS: CCDS12419, CCDS46035

Canonical transcript exons

ENST00000262643 — 12 exons

Exon	Start	End
ENSE00000694528	29812969	29813037
ENSE00000694530	29817137	29817282
ENSE00000694534	29817406	29817541
ENSE00000694536	29820702	29820848
ENSE00000694538	29821722	29821817
ENSE00000694540	29821996	29822130
ENSE00000995804	29812689	29812776
ENSE00001101798	29812532	29812578
ENSE00001262604	29811991	29812152
ENSE00003492114	29822240	29822351
ENSE00003623199	29822446	29822603
ENSE00003841238	29823655	29824312

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 96.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.4843 / max 301.3804, expressed in 1548 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175010	7.3112	1544
208767	0.1731	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.58	gold quality
oocyte	CL:0000023	96.46	gold quality
adrenal tissue	UBERON:0018303	90.11	gold quality
placenta	UBERON:0001987	90.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.92	gold quality
decidua	UBERON:0002450	84.90	gold quality
bone marrow	UBERON:0002371	81.88	gold quality
left testis	UBERON:0004533	81.76	gold quality
right testis	UBERON:0004534	81.67	gold quality
amniotic fluid	UBERON:0000173	81.50	gold quality
testis	UBERON:0000473	81.25	gold quality
lower esophagus mucosa	UBERON:0035834	80.95	gold quality
gingival epithelium	UBERON:0001949	80.30	silver quality
mucosa of transverse colon	UBERON:0004991	80.20	gold quality
right adrenal gland cortex	UBERON:0035827	80.05	gold quality
trabecular bone tissue	UBERON:0002483	79.80	gold quality
right adrenal gland	UBERON:0001233	79.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.95	gold quality
left adrenal gland cortex	UBERON:0035825	78.05	gold quality
left adrenal gland	UBERON:0001234	77.94	gold quality
stromal cell of endometrium	CL:0002255	77.93	gold quality
adrenal cortex	UBERON:0001235	77.49	gold quality
adrenal gland	UBERON:0002369	77.47	gold quality
parotid gland	UBERON:0001831	76.86	gold quality
bone marrow cell	CL:0002092	76.76	gold quality
gingiva	UBERON:0001828	76.74	silver quality
cerebellar hemisphere	UBERON:0002245	76.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.30	gold quality
cerebellar cortex	UBERON:0002129	76.25	gold quality
rectum	UBERON:0001052	75.56	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	1385.75
E-MTAB-7052	yes	59.60
E-ANND-3	yes	5.57
E-MTAB-8060	no	1428.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARNT, CBX7, CEBPA, CEBPB, CIC, DDX3X, E2F1, E2F2, E2F3, E2F4, EP300, EPCAM, ESR1, ESR2, EWSR1, EZH2, FLI1, FOSB, FOXC1, FOXM1, HBP1, HDAC2, HES1, HMGA1, HR, IRF1, KAT7, KLF4, KLF5, L3MBTL1, LGMN, LRRC4, MYC, MYCN, MYCT1, MYOD1, NANOG, NCOA3, NFKB, NKX6-1

miRNA regulators (miRDB)

59 targeting CCNE1, 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-9-5P	100.00	72.28	2361
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195

Literature-anchored findings (GeneRIF, showing 40)

• This study identifies cyclin E1 as a target for activation by ionizing radiation and which plays a functional role in apoptosis of hematopoietic cells. Run-on analyses indicated a predominantly transcriptional regulation of cyclin E. (PMID:10851086)
• TSG101 expression in gynecological tumors: relationship to cyclin D1, cyclin E, p53 and p16 proteins. (PMID:11838966)
• Retinoic acid-induced cell cycle arrest of human myeloid cell lines is associated with sequential down-regulation of c-Myc and cyclin E. (PMID:11877298)
• Proteolytic cleavage of cyclin E leads to inactivation of associated kinase activity and amplification of apoptosis in hematopoietic cells (PMID:11884622)
• 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)
• Cyclin E is a target of WT1 transcriptional repression (PMID:11919196)
• Ectopic expression of cyclin E in estrogen responsive cells abrogates antiestrogen mediated growth arrest. (PMID:12096339)
• The cyclin D1 high and cyclin E high subgroups of breast cancer: separate pathways in tumorogenesis based on pattern of genetic aberrations and inactivation of the pRb node. (PMID:12096344)
• regulates cell cycle (PMID:12101670)
• function and clinical value of cyclin E and p27 in adult acute leukemia (AL) (PMID:12133429)
• 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)
• human cytomegalovirus immediate-early protein 2 can activate cyclin E independent of the cell-cycle state (PMID:12533700)
• A 2.7 A X-ray crystal structure of a Skp1-Cdc4 complex bound to a high-affinity CPD phosphopeptide from human cyclin E reveals a core CPD motif, Leu-Leu-pThr-Pro, bound to an eight-bladed WD40 propeller domain in Cdc4 (PMID:12553912)
• 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)
• overexpression of cyclin D3 and cyclin E was mutually exclusive possibly reflecting different underlying pathways inducing deregulated expression of these cyclins (PMID:12647795)
• Data suggest that the interaction between PKCeta and cyclin E is carefully regulated, and is correlated with the inactivated form of the cyclin E/Cdk2 complex. (PMID:12729791)
• results show that cyclin D2 is complexed with p27, leading to a model for testicular germ cell tumors whereby the overexpression of cyclin D2 leads to the functional sequestration of p27 in the presence of CCNE and CCND2, favoring cell proliferation (PMID:12777997)
• High levels of this protein are found in malignant glioma. (PMID:12778072)
• Up-regulation of cyclin E is associated with spindle-cell sarcoma (PMID:12824885)
• p220 is an essential downstream component of the cyclin E/Cdk2 signaling pathway and functions to coordinate multiple elements of the G1/S transition. (PMID:14612403)
• CDK2-cyclin E, without prior CDK4-cyclin D activity, can phosphorylate and inactivate pRb, activate E2F, and induce DNA synthesis. (PMID:14645251)
• Assessment of p21, p27, Bax, and cyclin E expression in tumor tissues have been reported to be useful as prognostic factors in head and neck squamous cell carcinoma. (PMID:14719078)
• This review summarizes what is known about the biological role of cyclin E1 and cyclin E2, their deregulation in cancer, and the opportunities they may provide as targets in clinical therapy. (PMID:14965268)
• Cyclin E low molecular weight forms have roles in ovarian tumorigenesis (PMID:15007381)
• The expression patterns of cyclin D1, cyclin E, p21/waf1 and p27/kip1 in inflammatory bowel disease (IBD) may indicate their contribution in epithelial cell turnover and their possible implication in IBD-related dysplasia-carcinoma. (PMID:15060836)
• study shows that cyclin E overproduction is of adverse prognostic significance in adrenocortical tumors (PMID:15191351)
• Cyclin E-mediated impairment of DNA replication provides a potential mechanism for chromosome instability observed as a consequence of cyclin E deregulation. (PMID:15197178)
• Our results demonstrate a physiologic role for TRIP-Br in coupling E2F to novel functions in the regulation of cyclin E expression during cell cycle progression to ensure the proper execution of DNA replication and the maintenance of genomic stability. (PMID:15467469)
• Cyclin E expression is significantly higher in clear cell than in serous ovarian carcinomas. Cyclin E expression is significantly related with p53 positivity. (PMID:15557791)
• We propose that such increased E2F activity stabilizes cyclin E and contributes to establish the high and persistent levels of the protein commonly found in human neoplasias. (PMID:15611651)
• crystal structure of phospho-CDK2 in complex with a truncated cyclin E1 (residues 81-363) at 2.25 A resolution (PMID:15660127)
• overexpressed in breast cancer development. (PMID:15665273)
• low molecular weight forms of cyclin E may contribute to tumorigenesis through their resistance to the inhibitory activities of p21 and p27 while sequestering these CKIs from the full-length cyclin E (PMID:15708847)
• Cyclin E expression may be characteristic for papillary thyroid carcinomas with a tendency to early metastasizing. (PMID:15709169)
• p16(INK4A) reconstitution in p16(INK4A)-deficient T-ALL cells induced cell cycle arrest in the presence of cyclin E and c-Myc expression, uncoupled growth from cell cycle progression and caused a sequential process of growth, differentiation and apoptosis (PMID:15800668)
• The decreased expression of p57(kip2) and/or overexpression of cyclinE protein and PCNA may contribute to the occurrence and progression of pancreatic cancer. (PMID:16124066)
• The genesis and invasion of ameloblastoma is associated with the cell proliferation and differentiation, and regulated by the higher expression of cyclin E and the lower expression of p21(WAF1) and p27(KIP1). (PMID:16191374)
• human CUL4B and cyclin E proteins interact with each other and the CUL4B complexes can polyubiquitinate the CUL4B-associated cyclin E (PMID:16322693)
• These findings suggested that cyclin E may play a role in suppressing the colony formation of CFU-GM by CKbeta8-1. (PMID:16391523)
• Cyclin-dependent kinases regulate the transcriptional activity of FOXM1c; a combination of three phosphorylation sites mediates the Cyclin E and Cyclin A/CDK2 effects. (PMID:16504183)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccne1	ENSDARG00000098622
mus_musculus	Ccne1	ENSMUSG00000002068
rattus_norvegicus	Ccne1	ENSRNOG00000014786
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): CCNP (ENSG00000105219), CCNJ (ENSG00000107443), CCND1 (ENSG00000110092), CCND3 (ENSG00000112576), CCNG1 (ENSG00000113328), CCNI (ENSG00000118816), CCND2 (ENSG00000118971), CCNA1 (ENSG00000133101), CCNB1 (ENSG00000134057), CCNJL (ENSG00000135083), CCNG2 (ENSG00000138764), CCNA2 (ENSG00000145386), CCNB3 (ENSG00000147082), CCNO (ENSG00000152669), CCNB2 (ENSG00000157456), CCNF (ENSG00000162063), CCNE2 (ENSG00000175305), CCNI2 (ENSG00000205089)

Protein

Protein identifiers

G1/S-specific cyclin-E1 — P24864 (reviewed: P24864)

All UniProt accessions (5): C9J2U0, I3L1Q9, I3L413, P24864, V5W5X2

UniProt curated annotations — full annotation on UniProt →

Function. Essential for the control of the cell cycle at the G1/S (start) transition.

Subunit / interactions. Interacts with CDK2 protein kinase to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Found in a complex with CDK2, CABLES1 and CCNA1. Part of a complex consisting of UHRF2, CDK2 and CCNE1. Interacts directly with UHRF2; the interaction ubiquitinates CCNE1 and appears to occur independently of CCNE1 phosphorylation. Interacts with INCA1.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in testis and placenta. Low levels in bronchial epithelial cells.

Post-translational modifications. Phosphorylation of both Thr-395 by GSK3 and Ser-399 by CDK2 creates a high affinity degron recognized by FBXW7, and accelerates degradation via the ubiquitin proteasome pathway. Phosphorylation at Thr-77 creates a low affinity degron also recognized by FBXW7. Ubiquitinated by UHRF2; appears to occur independently of phosphorylation.

Miscellaneous. Lacks 49 residues within the cyclin box and cannot complex with CDK2.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P24864-1	E1L, E-L	yes
P24864-2	E1S
P24864-3	3, E-S

RefSeq proteins (4): NP_001229, NP_001309188, NP_001309190, NP_001309191 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004367	Cyclin_C-dom	Domain
IPR006671	Cyclin_N	Domain
IPR013763	Cyclin-like_dom	Domain
IPR036915	Cyclin-like_sf	Homologous_superfamily
IPR039361	Cyclin	Family
IPR048258	Cyclins_cyclin-box	Conserved_site

Pfam: PF00134, PF02984

UniProt features (36 total): helix 16, modified residue 5, turn 4, strand 3, region of interest 2, splice variant 2, compositionally biased region 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
8VQ3	X-RAY DIFFRACTION	1.84
8VQ4	X-RAY DIFFRACTION	1.9
9OB4	X-RAY DIFFRACTION	1.95
9OB3	X-RAY DIFFRACTION	1.98
9OB6	X-RAY DIFFRACTION	2
9OB5	X-RAY DIFFRACTION	2.1
9OB2	X-RAY DIFFRACTION	2.12
1W98	X-RAY DIFFRACTION	2.15
9GOP	X-RAY DIFFRACTION	2.16
7KJS	X-RAY DIFFRACTION	2.19
9BJC	X-RAY DIFFRACTION	2.22
7XQK	X-RAY DIFFRACTION	2.25
8H6P	X-RAY DIFFRACTION	2.44
9GP3	X-RAY DIFFRACTION	2.45
9D0V	X-RAY DIFFRACTION	2.54
8H4R	X-RAY DIFFRACTION	2.75
5L2W	X-RAY DIFFRACTION	2.8
9D0X	ELECTRON MICROSCOPY	2.84
9NYQ	X-RAY DIFFRACTION	2.85
9D0W	ELECTRON MICROSCOPY	2.95
8H6T	X-RAY DIFFRACTION	3
9NYR	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P24864-F1	80.13	0.66

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 (5): 77, 103, 387, 395, 399

Function

Pathways and Gene Ontology

Reactome pathways

46 pathways

ID	Pathway
R-HSA-1538133	G0 and Early G1
R-HSA-187577	SCF(Skp2)-mediated degradation of p27/p21
R-HSA-2559586	DNA Damage/Telomere Stress Induced Senescence
R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis
R-HSA-6804116	TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest
R-HSA-69017	CDK-mediated phosphorylation and removal of Cdc6
R-HSA-69200	Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes
R-HSA-69202	Cyclin E associated events during G1/S transition
R-HSA-69205	G1/S-Specific Transcription
R-HSA-69231	Cyclin D associated events in G1
R-HSA-69563	p53-Dependent G1 DNA Damage Response
R-HSA-8849470	PTK6 Regulates Cell Cycle
R-HSA-9661069	Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)
R-HSA-9706019	RHOBTB3 ATPase cycle
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-2559583	Cellular Senescence
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-390466	Chaperonin-mediated protein folding
R-HSA-391251	Protein folding
R-HSA-392499	Metabolism of proteins
R-HSA-453279	Mitotic G1 phase and G1/S transition
R-HSA-6791312	TP53 Regulates Transcription of Cell Cycle Genes
R-HSA-69052	Switching of origins to a post-replicative state
R-HSA-69206	G1/S Transition
R-HSA-69236	G1 Phase
R-HSA-69239	Synthesis of DNA

MSigDB gene sets: 468 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_DNA_REPLICATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_G1_S_SPECIFIC_TRANSCRIPTION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, BROWNE_HCMV_INFECTION_8HR_UP, FISCHER_G1_S_CELL_CYCLE, REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21, PID_PRL_SIGNALING_EVENTS_PATHWAY, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP

GO Biological Process (13): G1/S transition of mitotic cell cycle (GO:0000082), negative regulation of transcription by RNA polymerase II (GO:0000122), telomere maintenance (GO:0000723), DNA replication initiation (GO:0006270), protein phosphorylation (GO:0006468), homologous chromosome pairing at meiosis (GO:0007129), Wnt signaling pathway (GO:0016055), regulation of protein localization (GO:0032880), cell division (GO:0051301), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), positive regulation of mesenchymal stem cell proliferation (GO:1902462), regulation of cell cycle (GO:0051726), chromosome organization involved in meiotic cell cycle (GO:0070192)

GO Molecular Function (4): kinase activity (GO:0016301), cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538), protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytosol (GO:0005829), cyclin E1-CDK2 complex (GO:0097134), cyclin-dependent protein kinase holoenzyme complex (GO:0000307)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Cyclin E associated events during G1/S transition	2
G1/S Transition	2
Mitotic G1 phase and G1/S transition	1
Cyclin A:Cdk2-associated events at S phase entry	1
Cellular Senescence	1
Chaperonin-mediated protein folding	1
TP53 Regulates Transcription of Cell Cycle Genes	1
Switching of origins to a post-replicative state	1
G1 Phase	1
p53-Dependent G1/S DNA damage checkpoint	1
Signaling by PTK6	1
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
RNA Polymerase II Transcription	1
Cellular responses to stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA metabolic process	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
telomere organization	1
DNA-templated DNA replication	1
phosphorylation	1
protein modification process	1
homologous chromosome segregation	1
chromosome organization involved in meiotic cell cycle	1
cell surface receptor signaling pathway	1
intracellular protein localization	1
regulation of localization	1
cellular process	1
G1/S transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
mesenchymal stem cell proliferation	1
regulation of mesenchymal stem cell proliferation	1
positive regulation of stem cell proliferation	1
cell cycle	1
regulation of cellular process	1
chromosome organization	1
meiotic cell cycle	1
meiotic cell cycle process	1
transferase activity, transferring phosphorus-containing groups	1
cyclin-dependent protein serine/threonine kinase activity	1
cyclin-dependent protein kinase regulator activity	1
kinase binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
cytoplasm	1

Protein interactions and networks

STRING

3312 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCNE1	CDK2	P24941	999
CCNE1	CDK4	P11802	896
CCNE1	CDKN1A	P38936	889
CCNE1	CDK6	Q00534	885
CCNE1	TP53	P04637	883
CCNE1	CCNL2	Q96S94	870
CCNE1	CDKN1B	P46527	843
CCNE1	CDK1	P06493	835
CCNE1	CCNA1	P78396	794
CCNE1	E2F2	Q14209	793
CCNE1	E2F1	Q01094	788
CCNE1	MYC	P01106	784
CCNE1	CDKN2A	P42771	779
CCNE1	SKP2	Q13309	772
CCNE1	RBL2	Q08999	770

IntAct

110 interactions, top by confidence:

A	B	Type	Score
CDK2	CCNA2	psi-mi:“MI:0914”(association)	0.980
CCNE1	CDK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.970
CDK2	CCNE1	psi-mi:“MI:0217”(phosphorylation reaction)	0.970
CDK2	CCNE1	psi-mi:“MI:0914”(association)	0.970
CCNE1	CDK2	psi-mi:“MI:0914”(association)	0.970
CDK2	CCNE1	psi-mi:“MI:0915”(physical association)	0.970
CDK2	CCNE1	psi-mi:“MI:0407”(direct interaction)	0.970
CCNE1	CDK2	psi-mi:“MI:0915”(physical association)	0.970
CDK2	CCNE2	psi-mi:“MI:0914”(association)	0.940
CDK2	CCNB1	psi-mi:“MI:0914”(association)	0.890
CDKN1B	CCNE1	psi-mi:“MI:0914”(association)	0.890
CCNE1	CDKN1B	psi-mi:“MI:0915”(physical association)	0.890
CDKN1A	CCNE2	psi-mi:“MI:0914”(association)	0.890
CCNE1	CDKN1B	psi-mi:“MI:2364”(proximity)	0.890
CDK2	CCNB2	psi-mi:“MI:0914”(association)	0.860

BioGRID (389): CCNE1 (Biochemical Activity), CCNE1 (Affinity Capture-Western), CCNE1 (Biochemical Activity), CCNE1 (Reconstituted Complex), CCNE1 (Biochemical Activity), CCNE1 (Affinity Capture-MS), CDK2 (Reconstituted Complex), Calm1 (Affinity Capture-Western), CDK2 (Reconstituted Complex), CCNE1 (Affinity Capture-MS), CCNE1 (Affinity Capture-MS), CCNE1 (Affinity Capture-MS), CCNE1 (Affinity Capture-MS), CCNE1 (Affinity Capture-MS), CDKN1B (Co-localization)

ESM2 similar proteins: A0A494C086, A0A494C0Z2, A0A494C191, A0JPH4, A6NHP3, A6NIY4, A6NJR5, A6NLX3, A6NNV3, A6QLI5, B0BNE4, O08918, O60543, O70302, O75916, P0CI01, P0DTA3, P0DUD1, P0DUD2, P0DUD3, P0DUD4, P0DUX0, P0DUX1, P0DV79, P24864, P39949, P49805, Q12967, Q495Y7, Q495Y8, Q4VXA5, Q4ZIN3, Q5IBH6, Q5IBH7, Q5MJ70, Q5SYB0, Q5XIQ2, Q5ZJR9, Q61457, Q6AYG1

Diamond homologs: A0MEB5, A2YH60, A5PK16, C4YR54, O15995, O48790, O77689, O95067, O96020, P04962, P07818, P0CY18, P10815, P13351, P13365, P15206, P18063, P20248, P20437, P20438, P20439, P24860, P24861, P24862, P24864, P24868, P24869, P24870, P24871, P25009, P25010, P25011, P25012, P29332, P30183, P30274, P30276, P30277, P30278, P30283

SIGNOR signaling

27 interactions.

A	Effect	B	Mechanism
CDK2	down-regulates	CCNE1	phosphorylation
GSK3B	down-regulates	CCNE1	phosphorylation
4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-pyrazole-3-carboxamide	down-regulates	CCNE1	“chemical inhibition”
4-[[5-amino-1-[(2,6-difluorophenyl)-oxomethyl]-1,2,4-triazol-3-yl]amino]benzenesulfonamide	down-regulates	CCNE1	“chemical inhibition”
CCNE1	up-regulates	CDK2	binding
R547	down-regulates	CCNE1	“chemical inhibition”
seliciclib	down-regulates	CCNE1	“chemical inhibition”
E2F1	“up-regulates quantity by expression”	CCNE1	“transcriptional regulation”
ARNT	“down-regulates quantity by repression”	CCNE1	“transcriptional regulation”
TFDP1	“up-regulates quantity by expression”	CCNE1	“transcriptional regulation”
MYCT1	“down-regulates quantity by repression”	CCNE1	“transcriptional regulation”
LRRC4	“down-regulates quantity by repression”	CCNE1	“transcriptional regulation”
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	CCNE1	polyubiquitination
FBXW7	“down-regulates quantity by destabilization”	CCNE1	binding
RHOBTB3	“down-regulates quantity by destabilization”	CCNE1	binding
“Cullin 3-RBX1-Skp1”	“down-regulates quantity by destabilization”	CCNE1	polyubiquitination
SKP2	“down-regulates quantity by destabilization”	CCNE1	binding
E2F2	“up-regulates quantity by expression”	CCNE1	“transcriptional regulation”
MYC	“up-regulates quantity by expression”	CCNE1	“transcriptional regulation”
SCF-SKP2	“down-regulates quantity by destabilization”	CCNE1	ubiquitination
UHRF2	“down-regulates quantity by destabilization”	CCNE1	ubiquitination
CCNE1	“form complex”	CyclinE1/CDK3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 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 Genes Involved in G1 Cell Cycle Arrest	6	109.8×	4e-10
TP53 Regulates Transcription of Cell Cycle Genes	7	97.6×	2e-11
p53-Dependent G1 DNA Damage Response	5	91.5×	4e-08
p53-Dependent G1/S DNA damage checkpoint	5	91.5×	4e-08
G1/S DNA Damage Checkpoints	5	86.1×	5e-08
Polo-like kinase mediated events	5	81.3×	6e-08
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	5	81.3×	6e-08
G0 and Early G1	6	67.6×	8e-09

GO biological processes:

GO term	Partners	Fold	FDR
DNA damage response, signal transduction by p53 class mediator	5	39.0×	2e-05
G1/S transition of mitotic cell cycle	8	34.9×	5e-08
G2/M transition of mitotic cell cycle	5	33.9×	4e-05
negative regulation of cell cycle	5	31.6×	5e-05
regulation of mitotic cell cycle	6	31.4×	6e-06
negative regulation of cell growth	6	18.8×	6e-05
regulation of cell cycle	10	16.2×	2e-07
cell division	11	11.0×	7e-07

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

Cyclin E, while currenly not as widely implicated as its cyclin D counterparts, has been implicated in various carcinomas, including breast, gastric, stomach and colorectal. High levels of cyclin E, either by gene amplification or overexpression, have been shown to lead to poorer prognosis in gastic carcinoma, and these measurements are correlated with later stage disease. In lung cancer, neoplastic cells with higher levels of the cyclin E/CDK2 complex are more radiosensitive than their more lowly expressed counterparts.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1003 predictions. Top by Δscore:

Variant	Effect	Δscore
19:29812149:CCTGG:C	donor_loss	1.0000
19:29812150:CTGG:C	donor_loss	1.0000
19:29812151:TGGTG:T	donor_loss	1.0000
19:29812152:GGTG:G	donor_loss	1.0000
19:29812153:G:C	donor_loss	1.0000
19:29812153:G:GG	donor_gain	1.0000
19:29812154:T:A	donor_loss	1.0000
19:29812684:CACA:C	acceptor_loss	1.0000
19:29812686:CA:C	acceptor_loss	1.0000
19:29812687:A:AC	acceptor_loss	1.0000
19:29812687:A:AG	acceptor_gain	1.0000
19:29812687:AG:A	acceptor_gain	1.0000
19:29812688:G:GG	acceptor_gain	1.0000
19:29812688:GG:G	acceptor_gain	1.0000
19:29812758:G:GT	donor_gain	1.0000
19:29812772:CCGTT:C	donor_gain	1.0000
19:29812774:GTT:G	donor_gain	1.0000
19:29812775:TT:T	donor_gain	1.0000
19:29812777:G:GG	donor_gain	1.0000
19:29813034:CCAGG:C	donor_loss	1.0000
19:29813035:CAGG:C	donor_loss	1.0000
19:29813036:AGG:A	donor_loss	1.0000
19:29813038:G:GA	donor_loss	1.0000
19:29813039:T:G	donor_loss	1.0000
19:29817129:A:AG	acceptor_gain	1.0000
19:29817130:T:G	acceptor_gain	1.0000
19:29817134:C:G	acceptor_gain	1.0000
19:29817134:CA:C	acceptor_loss	1.0000
19:29817135:A:AG	acceptor_gain	1.0000
19:29817136:G:GT	acceptor_gain	1.0000

AlphaMissense

2720 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:29817530:T:A	W151R	1.000
19:29817530:T:C	W151R	1.000
19:29817532:G:C	W151C	0.999
19:29817532:G:T	W151C	0.999
19:29820763:G:C	R175P	0.999
19:29820835:C:A	A199E	0.999
19:29820837:G:C	A200P	0.999
19:29820842:A:C	K201N	0.999
19:29820842:A:T	K201N	0.999
19:29821801:A:T	E230V	0.999
19:29822005:T:A	W239R	0.999
19:29822005:T:C	W239R	0.999
19:29820813:G:T	G192W	0.998
19:29820814:G:A	G192E	0.998
19:29820841:A:T	K201I	0.998
19:29817522:T:C	L148P	0.997
19:29817531:G:C	W151S	0.997
19:29820706:G:A	C156Y	0.997
19:29820707:T:G	C156W	0.997
19:29820721:T:C	L161P	0.997
19:29820744:G:C	A169P	0.997
19:29820813:G:A	G192R	0.997
19:29820813:G:C	G192R	0.997
19:29820834:G:C	A199P	0.997
19:29820838:C:A	A200D	0.997
19:29822000:T:C	L237P	0.997
19:29822007:G:C	W239C	0.997
19:29822007:G:T	W239C	0.997
19:29822035:T:A	W249R	0.997
19:29822035:T:C	W249R	0.997

dbSNP variants (sampled 300 via entrez): RS1000345404 (19:29811839 G>A), RS1000514115 (19:29824675 G>A), RS1000522945 (19:29818350 CGG>C,CGGG), RS1000533643 (19:29812899 T>C), RS1000621456 (19:29824626 A>G), RS1000640438 (19:29818461 A>G,T), RS1000794846 (19:29818675 A>C), RS1000897313 (19:29813196 G>A,T), RS1001132129 (19:29812926 T>G), RS1001517650 (19:29818884 T>C), RS1001591214 (19:29819130 A>G), RS1002014698 (19:29824084 T>C), RS1002038229 (19:29813290 C>T), RS1002472685 (19:29813547 C>T), RS1002751962 (19:29821134 C>A,T)

Disease associations

OMIM: gene MIM:123837 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000842_4	Bladder cancer	2.000000e-11
GCST002240_9	Bladder cancer	1.000000e-11
GCST002783_298	Body mass index	3.000000e-06
GCST002783_554	Body mass index	5.000000e-06
GCST003487_5	Response to fenofibrate (total cholesterol levels)	9.000000e-06
GCST004280_33	Diastolic blood pressure	1.000000e-09
GCST005076_39	Breast cancer (estrogen-receptor negative)	2.000000e-07
GCST005077_7	Breast cancer	7.000000e-09
GCST007094_2	Diastolic blood pressure	3.000000e-10
GCST007928_79	Medication use (diuretics)	3.000000e-10
GCST009306_21	Spatial processing	4.000000e-08
GCST010988_20	Adult body size	6.000000e-15
GCST011122_15	Walking pace	1.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007806	total cholesterol change measurement
EFO:0006336	diastolic blood pressure
EFO:0009928	Diuretic use measurement
EFO:0008354	cognitive function measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (10): CHEMBL1907605 (PROTEIN COMPLEX), CHEMBL2094126 (PROTEIN COMPLEX), CHEMBL2111444 (PROTEIN COMPLEX GROUP), CHEMBL3038468 (PROTEIN COMPLEX), CHEMBL3038471 (PROTEIN COMPLEX), CHEMBL3617 (SINGLE PROTEIN), CHEMBL3885554 (PROTEIN COMPLEX), CHEMBL4523715 (PROTEIN-PROTEIN INTERACTION), CHEMBL5483189 (PROTEIN COMPLEX GROUP), CHEMBL6195580 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

38 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 72,909 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL3894860	TRILACICLIB	4	2,086
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL599552	INDIGO	3	6,024
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL1276127	INDIRUBIN	2	181
CHEMBL14762	SELICICLIB	2	3,787
CHEMBL1944698	ZOTIRACICLIB	2	2,915
CHEMBL3115681	NARAZACICLIB	2	287
CHEMBL3655762	CYC-065	2	388
CHEMBL4094440	BMS-919373	2	28
CHEMBL4277900	CROZBACICLIB	2	18
CHEMBL4297488	CT-7001	2	379
CHEMBL4297644	SIMUROSERTIB	2	63
CHEMBL4442620	RONICICLIB	2	367
CHEMBL4446357	EBVACICLIB	2	599
CHEMBL445813	AT-7519	2	2,614
CHEMBL4462530	ZEMIRCICLIB	2
CHEMBL5095094	CULMERCICLIB	2
CHEMBL5201870	TEGTOCICLIB	2
CHEMBL564829	MILCICLIB	2
CHEMBL575448	BMS-754807	2
CHEMBL2347597	ASNUCICLIB	2
CHEMBL5199065	ISTISOCICLIB	2
CHEMBL1230607	PHA-793887	1
CHEMBL258805	SU-9516	1
CHEMBL296468	BMS-387032	1

Clinical evidence (CIViC)

Drug × variant × indication: 12 predictive associations from 12 curated evidence items; also 4 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
CCNE1 Underexpression	Fulvestrant + Palbociclib	Breast Cancer	Sensitivity/Response	CIViC B	EID7331
CCNE1 Amplification	Taselisib + Fadraciclib	Endometrial Serous Adenocarcinoma	Sensitivity/Response	CIViC D	EID10181
CCNE1 Amplification	Lunresertib + Camonsertib	Ovarian Carcinoma	Sensitivity/Response	CIViC D	EID12761
CCNE1 Amplification	Lunresertib + Camonsertib	Endometrial Carcinoma	Sensitivity/Response	CIViC D	EID12762
CCNE1 Amplification	Akt Inhibitor MK2206 + Dinaciclib	Ovarian Serous Cystadenocarcinoma	Sensitivity/Response	CIViC D	EID1735
CCNE1 Amplification	Dinaciclib	Ovarian Cancer	Sensitivity/Response	CIViC D	EID7791
CCNE1 Amplification	Dinaciclib + Cisplatin	Ovarian Cancer	Sensitivity/Response	CIViC D	EID7799
CCNE1 Overexpression	CDK Inhibitor SNS-032 + Palbociclib	Breast Cancer	Sensitivity/Response	CIViC D	EID10183
CCNE1 Overexpression	CDK Inhibitor SNS-032	Ovarian Cancer	Sensitivity/Response	CIViC D	EID1734
CCNE1 Amplification	Palbociclib	Estrogen-receptor Positive Breast Cancer	Resistance	CIViC D	EID1629
CCNE1 Overexpression	Palbociclib	Breast Cancer	Resistance	CIViC D	EID10182
CCNE1 Overexpression	Palbociclib	Ovarian Cancer	Resistance	CIViC D	EID7792

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

Binding affinities (BindingDB)

1349 measured of 1639 human assays (1797 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-({6-(2-hydroxyethyl)-8-[(1R,2S)-2-methylcyclopentyl]-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl}amino)-N-methylpiperidine-1-sulfonamide	KI	0.06 nM	US-10233188: CDK2/4/6 inhibitors
6-methyl-8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.06 nM	US-10233188: CDK2/4/6 inhibitors
6-(2-hydroxyethyl)-8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.08 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(1-methylimidazol-4-yl)sulfonylpiperidin-4-yl]amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.08 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.08 nM	US-10233188: CDK2/4/6 inhibitors
US10233188, Example 187	KI	0.08 nM	US-10233188: CDK2/4/6 inhibitors
4-[[6-(2,2-difluoroethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.09 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.09 nM	US-10233188: CDK2/4/6 inhibitors
N-methyl-4-[[8-[(1R,2S)-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]piperidine-1-sulfonamide	KI	0.09 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.09 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(1-methylpyrazol-4-yl)sulfonylpiperidin-4-yl]amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.1 nM	US-10233188: CDK2/4/6 inhibitors
2-[(1-ethylsulfonylpiperidin-4-yl)amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methylpyrido[2,3-d]pyrimidin-7-one	KI	0.1 nM	US-10233188: CDK2/4/6 inhibitors
BDBM467191	KI	0.1 nM	US-10233188: CDK2/4/6 inhibitors
6-(2-hydroxyethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.11 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(2-methoxyethylsulfonyl)piperidin-4-yl]amino]-8-[(1R,2S)-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.12 nM	US-10233188: CDK2/4/6 inhibitors
2-[(1-cyclopropylsulfonylpiperidin-4-yl)amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methylpyrido[2,3-d]pyrimidin-7-one	KI	0.12 nM	US-10233188: CDK2/4/6 inhibitors
4-[[6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]piperidine-1-sulfonamide	KI	0.12 nM	US-10233188: CDK2/4/6 inhibitors
US10233188, Example 201	KI	0.12 nM	US-10233188: CDK2/4/6 inhibitors
US10233188, Example 221	KI	0.13 nM	US-10233188: CDK2/4/6 inhibitors
N-(2,2-difluoropropyl)-4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]piperidine-1-sulfonamide	KI	0.14 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(1,1-dioxothiolan-3-yl)sulfonylpiperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methylpyrido[2,3-d]pyrimidin-7-one	KI	0.14 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(cyclopropylmethylsulfonyl)piperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methylpyrido[2,3-d]pyrimidin-7-one	KI	0.15 nM	US-10233188: CDK2/4/6 inhibitors
6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)-piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.16 nM	US-10233188: CDK2/4/6 inhibitors
2-[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]-7-oxopyrido[2,3-d]pyrimidin-6-yl]acetonitrile	KI	0.16 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(2-methoxyethylsulfonyl)piperidin-4-yl]amino]-6-methylpyrido[2,3-d]pyrimidin-7-one	KI	0.17 nM	US-10233188: CDK2/4/6 inhibitors
4-[[6-(difluoromethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.17 nM	US-10233188: CDK2/4/6 inhibitors
4-[(8-cyclopentyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]piperidine-1-sulfonamide	KI	0.19 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.2 nM	US-10233188: CDK2/4/6 inhibitors
2-[(1-cyclopropylsulfonylpiperidin-4-yl)amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.2 nM	US-10233188: CDK2/4/6 inhibitors
4-[[6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.2 nM	US-10233188: CDK2/4/6 inhibitors
N-(2,2-difluoropropyl)-4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]piperidine-1-sulfonamide	KI	0.21 nM	US-10233188: CDK2/4/6 inhibitors
2-[(1-ethylsulfonylpiperidin-4-yl)amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.21 nM	US-10233188: CDK2/4/6 inhibitors
4-[(8-cyclopentyl-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]piperidine-1-sulfonamide	KI	0.22 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-(oxan-4-yl)piperidine-1-sulfonamide	KI	0.24 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-[[(2R)-oxolan-2-yl]methyl]piperidine-1-sulfonamide	KI	0.24 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(1,1-dioxothiolan-3-yl)sulfonylpiperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.25 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(1,3-thiazol-2-ylsulfonyl)piperidin-4-yl]amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.25 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(1,3,4-thiadiazol-2-ylsulfonyl)piperidin-4-yl]amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.25 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(cyclopropylmethylsulfonyl)piperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.25 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,3R)-3-hydroxycyclohexyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]-amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.26 nM	US-10233188: CDK2/4/6 inhibitors
6-chloro-8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.27 nM	US-10233188: CDK2/4/6 inhibitors
2-[8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]-7-oxopyrido[2,3-d]pyrimidin-6-yl]acetamide	KI	0.27 nM	US-10233188: CDK2/4/6 inhibitors
6-(hydroxymethyl)-8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.27 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(fluoromethylsulfonyl)piperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.27 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-[[(2S)-oxolan-2-yl]methyl]piperidine-1-sulfonamide	KI	0.27 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.28 nM	US-10233188: CDK2/4/6 inhibitors
4-[(8-cycloheptyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]piperidine-1-sulfonamide	KI	0.29 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-(2-methoxy-2-methylpropyl)piperidine-1-sulfonamide	KI	0.33 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-2-[[1-(2,2,2-trifluoroethylsulfonyl)piperidin-4-yl]amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.34 nM	US-10233188: CDK2/4/6 inhibitors
8-cycloheptyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.35 nM	US-10233188: CDK2/4/6 inhibitors

ChEMBL bioactivities

3595 potent at pChembl≥5 of 3865 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.40	Ki	0.04	nM	CHEMBL5899718
10.30	Ki	0.05	nM	CHEMBL5762472
10.22	Ki	0.06	nM	CHEMBL5774115
10.22	Ki	0.06	nM	CHEMBL5817327
10.22	Ki	0.06	nM	CHEMBL5857215
10.15	Ki	0.07	nM	CHEMBL5808436
10.15	Ki	0.07	nM	CHEMBL5975537
10.10	Ki	0.08	nM	CHEMBL5764489
10.10	Ki	0.08	nM	CHEMBL5877168
10.10	Ki	0.08	nM	CHEMBL5278622
10.10	Ki	0.08	nM	CHEMBL5963572
10.10	Ki	0.08	nM	CHEMBL5805501
10.10	Ki	0.08	nM	CHEMBL5876770
10.10	Ki	0.08	nM	CHEMBL5975537
10.05	Ki	0.09	nM	CHEMBL4750658
10.05	Ki	0.09	nM	CHEMBL5281770
10.05	Ki	0.09	nM	CHEMBL5746772
10.05	Ki	0.09	nM	CHEMBL5967788
10.05	Ki	0.09	nM	CHEMBL6005561
10.05	Ki	0.09	nM	CHEMBL5281860
10.05	Ki	0.09	nM	CHEMBL5765623
10.05	Ki	0.09	nM	CHEMBL5813951
10.05	Ki	0.09	nM	CHEMBL5805501
10.05	Ki	0.09	nM	CHEMBL5994701
10.00	Ki	0.1	nM	CHEMBL4744945
10.00	Ki	0.1	nM	CHEMBL4797526
10.00	Ki	0.1	nM	CHEMBL5950749
10.00	Ki	0.1	nM	CHEMBL6042439
10.00	Ki	0.1	nM	CHEMBL6047683
10.00	Ki	0.1	nM	CHEMBL5804029
10.00	Ki	0.1	nM	CHEMBL5776785
10.00	Ki	0.1	nM	CHEMBL5909080
10.00	Ki	0.1	nM	CHEMBL5883663
10.00	Ki	0.1	nM	CHEMBL5893129
9.96	Ki	0.11	nM	CHEMBL5281860
9.96	Ki	0.11	nM	CHEMBL5964436
9.96	Ki	0.11	nM	CHEMBL5921041
9.96	Ki	0.11	nM	CHEMBL5828800
9.96	Ki	0.11	nM	CHEMBL5886881
9.96	Ki	0.11	nM	CHEMBL6022715
9.96	Ki	0.11	nM	CHEMBL5948920
9.92	Ki	0.12	nM	CHEMBL4764153
9.92	Ki	0.12	nM	CHEMBL4748471
9.92	Ki	0.12	nM	EBVACICLIB
9.92	Ki	0.12	nM	CHEMBL5278622
9.92	Ki	0.12	nM	CHEMBL5847372
9.92	Ki	0.12	nM	CHEMBL5900389
9.92	Ki	0.12	nM	CHEMBL5816880
9.92	Ki	0.12	nM	CHEMBL5756851
9.89	Ki	0.13	nM	EBVACICLIB

PubChem BioAssay actives

2477 with measured affinity, of 4547 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
6-(2,2-difluoroethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933531: Inhibition of CDK2/cyclin E1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0001	uM
6-(difluoromethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
6-(2,2-difluoroethyl)-8-[(1S,2S)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933531: Inhibition of CDK2/cyclin E1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0001	uM
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933531: Inhibition of CDK2/cyclin E1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0001	uM
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]piperidine-1-sulfonamide	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
8-[(1R,2S,3R)-3-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
[(1S,3R)-3-[3-[[2-(6-methoxy-3-pyridinyl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] 2,2-dimethylazetidine-1-carboxylate	1678540: Inhibition of recombinant full length wild-type CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
[(1R,3S)-3-[3-[[2-(6-methoxy-3-pyridinyl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] 2,2-dimethylazetidine-1-carboxylate	1678540: Inhibition of recombinant full length wild-type CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
[(1R,3S)-3-[3-[[2-(2-methyl-1,3-thiazol-5-yl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] (2S,3R)-3-cyano-2-methylazetidine-1-carboxylate	1678540: Inhibition of recombinant full length wild-type CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
[(2S)-2-methylazetidin-1-yl]-[2-[(1-methylsulfonylpiperidin-4-yl)amino]quinazolin-7-yl]methanone	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0001	uM
6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933531: Inhibition of CDK2/cyclin E1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0002	uM
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0002	uM
4-[[6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0002	uM
2-[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]-7-oxopyrido[2,3-d]pyrimidin-6-yl]acetonitrile	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0002	uM
[(1R,3S)-3-[3-[[2-(6-methoxy-3-pyridinyl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] (2S,3R)-3-cyano-2-methylazetidine-1-carboxylate	1678540: Inhibition of recombinant full length wild-type CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0002	uM
3-fluoro-4-[[7-[(2S,3R)-3-methoxy-2-methylazetidine-1-carbonyl]pyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylbenzenesulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0002	uM
N,3-dimethyl-4-[[7-[(2S)-2-methylpyrrolidine-1-carbonyl]quinazolin-2-yl]amino]benzenesulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0002	uM
ethyl 2-[(2E)-2-[1-(6-chloro-2-oxo-3,4-dihydrochromen-3-yl)ethylidene]hydrazinyl]-4-methyl-1,3-thiazole-5-carboxylate	1927555: Inhibition of CDK2/cyclin E1 (unknown origin) incubated for 60 mins in presence of ATP by ADP-Glo luminescent Kinase Assay	ic50	0.0002	uM
ethyl 2-[(2E)-2-[1-(6-bromo-2-oxo-3,4-dihydrochromen-3-yl)ethylidene]hydrazinyl]-4-methyl-1,3-thiazole-5-carboxylate	1927555: Inhibition of CDK2/cyclin E1 (unknown origin) incubated for 60 mins in presence of ATP by ADP-Glo luminescent Kinase Assay	ic50	0.0002	uM
4-[[7-[(2S)-2-methylpyrrolidine-1-carbonyl]quinazolin-2-yl]amino]piperidine-1-sulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0002	uM
3-fluoro-4-[[7-[(2S,3R)-3-fluoro-2-methylazetidine-1-carbonyl]pyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylbenzenesulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0002	uM
3-fluoro-N-methyl-4-[[7-[(2S)-2-methylazetidine-1-carbonyl]pyrido[2,3-d]pyrimidin-2-yl]amino]benzenesulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0002	uM
[(2R)-2-methylpyrrolidin-1-yl]-[2-[(1-methylsulfonylpiperidin-4-yl)amino]quinazolin-7-yl]methanone	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0002	uM
4-[(8-cycloheptyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]piperidine-1-sulfonamide	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0003	uM
2-[[1-(cyclopropylmethylsulfonyl)piperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0003	uM
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	1685181: Inhibition of recombinant full length wild-type phosphorylated CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0003	uM
4-[[7’-[(1R,3R)-3-hydroxycyclohexyl]-6’-oxospiro[cyclopropane-1,5’-pyrrolo[2,3-d]pyrimidine]-2’-yl]amino]-N-methylbenzenesulfonamide	1875689: Inhibition of recombinant human N-terminal GST-tagged full-length CDK2/Flag-tagged cyclinE1 expressed in baculovirus expression system using eIF4E-binding protein-1 peptide as substrate incubated for 1 hr in presence of ATP by HTRF assay	ic50	0.0003	uM
N-methyl-4-[[7’-[(1S,2S)-2-methylcyclopentyl]-6’-oxospiro[cyclopropane-1,5’-pyrrolo[2,3-d]pyrimidine]-2’-yl]amino]benzenesulfonamide	1875689: Inhibition of recombinant human N-terminal GST-tagged full-length CDK2/Flag-tagged cyclinE1 expressed in baculovirus expression system using eIF4E-binding protein-1 peptide as substrate incubated for 1 hr in presence of ATP by HTRF assay	ic50	0.0003	uM
N-[1-(1-methylimidazol-4-yl)sulfonylpiperidin-4-yl]-4-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-5-(trifluoromethyl)pyrimidin-2-amine	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0003	uM
2-[(1-pyridin-2-ylsulfonylpiperidin-4-yl)amino]-4-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]pyrimidine-5-carbonitrile	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0003	uM
1-[4-[2-[(1-cyclopropylsulfonylpiperidin-4-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]pyrazol-1-yl]-2-methylpropan-2-ol	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0003	uM
2-[[1-(1-methylimidazol-4-yl)sulfonylpiperidin-4-yl]amino]-4-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]pyrimidine-5-carbonitrile	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0003	uM
3-chloro-4-[4-[2-[(1-methylsulfonylpiperidin-4-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]pyrazol-1-yl]benzonitrile	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0003	uM
4-[[7’-[(1R,2R)-2-methylcyclopentyl]-6’-oxospiro[cyclopropane-1,5’-pyrrolo[2,3-d]pyrimidine]-2’-yl]amino]-N-[(3R)-1-methylpiperidin-3-yl]benzenesulfonamide	1875689: Inhibition of recombinant human N-terminal GST-tagged full-length CDK2/Flag-tagged cyclinE1 expressed in baculovirus expression system using eIF4E-binding protein-1 peptide as substrate incubated for 1 hr in presence of ATP by HTRF assay	ic50	0.0003	uM
N-methyl-4-[[7-[(2S)-2-methylpyrrolidine-1-carbonyl]quinazolin-2-yl]amino]benzenesulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0003	uM
8-cycloheptyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933531: Inhibition of CDK2/cyclin E1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0004	uM
4-[1-[2-chloro-4-(methylaminomethyl)phenyl]pyrazol-4-yl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0004	uM
2-methyl-1-[4-[2-[(1-methylsulfonylpiperidin-4-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]pyrazol-1-yl]propan-2-ol	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0004	uM
N-[1-(1-methylpyrazol-4-yl)sulfonylpiperidin-4-yl]-4-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-5-(trifluoromethyl)pyrimidin-2-amine	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0004	uM
4-[[7-[(2S,3R)-3-cyano-2-methylazetidine-1-carbonyl]pyrido[2,3-d]pyrimidin-2-yl]amino]-3-fluoro-N-methylbenzenesulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0004	uM
[(1S,3R)-3-[3-[[2-(6-methoxy-3-pyridinyl)acetyl]amino]-1H-pyrazol-5-yl]cyclopentyl] N-(4-hydroxycyclohexyl)carbamate	1678540: Inhibition of recombinant full length wild-type CDK2/Cyclin E1 (unknown origin) expressed in baculovirus expression system assessed as reduction in production of ADP using 5-FAM-QSPKKG-CONH2 peptide as substrate preincubated with enzyme for 15 mins followed by further incubation with ATP for 45 mins by fluorescence-based microfluidic mobility shift assay	ki	0.0005	uM
4-[1-[2-chloro-4-(methylaminomethyl)phenyl]pyrazol-4-yl]-N-(1-methylsulfonylpiperidin-4-yl)-5-(trifluoromethyl)pyrimidin-2-amine	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0005	uM
4-[[7-[(2S,4S)-4-fluoro-2-methylpyrrolidine-1-carbonyl]quinazolin-2-yl]amino]-N,3-dimethylbenzenesulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0005	uM
7-butyl-6-(4-methoxyphenyl)-5H-pyrrolo[2,3-b]pyrazine	661600: Inhibition of human recombinant CDK2/CycE using HHASPRK as substrate by ESI-MS analysis	ki	0.0005	uM
8-cyclopentyl-6-methyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933531: Inhibition of CDK2/cyclin E1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0006	uM
4-[[7’-(2-chloro-5-fluorophenyl)-6’-oxospiro[cyclopropane-1,5’-pyrrolo[2,3-d]pyrimidine]-2’-yl]amino]-N-methylbenzenesulfonamide	1875689: Inhibition of recombinant human N-terminal GST-tagged full-length CDK2/Flag-tagged cyclinE1 expressed in baculovirus expression system using eIF4E-binding protein-1 peptide as substrate incubated for 1 hr in presence of ATP by HTRF assay	ic50	0.0006	uM
4-[1-(2-chlorophenyl)pyrazol-4-yl]-N-(1-methylsulfonylpiperidin-4-yl)-5-(trifluoromethyl)pyrimidin-2-amine	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0006	uM
2-[(1-cyclopropylsulfonylpiperidin-4-yl)amino]-4-[1-(2-hydroxy-2-methylpropyl)pyrazol-4-yl]pyrimidine-5-carbonitrile	2089226: Inhibition of N-terminal GST-tagged full-length human CDK2(1 to 298 residues) /FLAG-tagged human Cyclin E1 (1 to 410 residues) expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by HTRF assay	ic50	0.0006	uM
4-[[7-[(2S,4S)-4-fluoro-2-methylpyrrolidine-1-carbonyl]pyrido[2,3-d]pyrimidin-2-yl]amino]-N,3-dimethylbenzenesulfonamide	2015520: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0006	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression, decreases reaction, increases reaction (+1 more)	9
Estradiol	decreases reaction, increases expression, increases reaction, increases cleavage	9
Resveratrol	affects expression, decreases reaction, increases expression, decreases expression	8
Arsenic Trioxide	decreases expression, decreases methylation, increases expression, affects expression, affects binding (+1 more)	8
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, decreases methylation	8
Quercetin	affects expression, decreases reaction, affects binding, increases reaction, decreases expression (+3 more)	7
Tretinoin	decreases reaction, increases expression, increases reaction, affects binding, affects cotreatment (+2 more)	7
Cadmium Chloride	affects cotreatment, decreases reaction, increases expression, increases abundance, increases reaction (+1 more)	7
Cisplatin	increases response to substance, increases expression, affects binding, decreases activity, decreases expression (+3 more)	6
Tamoxifen	affects expression, affects reaction, affects binding, affects cotreatment, increases reaction (+4 more)	6
Fulvestrant	affects cotreatment, decreases reaction, increases expression, increases reaction, decreases expression	5
Benzo(a)pyrene	increases expression, increases methylation, decreases expression, decreases methylation	5
Cadmium	affects binding, affects reaction, decreases reaction, increases abundance, increases expression (+1 more)	5
Fluorouracil	affects cotreatment, decreases expression, increases expression	5
sodium arsenite	increases expression, decreases expression, increases abundance, affects reaction	4
U 0126	affects cotreatment, decreases expression, decreases reaction, increases cleavage, increases expression	4
palbociclib	decreases response to substance, decreases expression, increases expression	4
Cannabidiol	decreases expression, affects cotreatment	4
perfluorooctanoic acid	affects expression, decreases expression	3
Troglitazone	affects response to substance, decreases expression, decreases activity, increases response to substance	3
Glyphosate	increases expression, decreases expression	3
Curcumin	increases degradation, decreases reaction, increases expression, decreases expression	3
Tobacco Smoke Pollution	decreases expression, increases expression	3
Aflatoxin B1	increases expression, increases methylation, affects cotreatment	3
Particulate Matter	decreases expression, decreases reaction, increases abundance, increases expression	3
naringenin	increases expression, decreases expression, affects cotreatment	2
trichostatin A	increases expression	2
indole-3-carbinol	increases reaction, decreases expression, affects localization, affects binding	2
afimoxifene	increases cleavage, affects reaction, decreases reaction, affects binding, affects cotreatment (+2 more)	2
manganese chloride	decreases expression, increases abundance	2

ChEMBL screening assays

691 unique, capped per target: 690 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1047830	Binding	Residual activity of CDK2/Cyclin E at 10 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem
CHEMBL4325185	ADMET	Inhibition of human CDK2/Cylcin E at 1 uM relative to control	Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5-b]pyridazines for the Treatment of Human African Trypanosomiasis. — J Med Chem

Cellosaurus cell lines

11 cell lines: 8 cancer cell line, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A0L9	SEES3-1V human CCNE1, clone1	Embryonic stem cell	Male
CVCL_A0M0	SEES3-1V human CCNE1, clone2	Embryonic stem cell	Male
CVCL_A0M1	SEES3-1V human CCNE1, clone3	Embryonic stem cell	Male
CVCL_B8CL	Abcam HCT 116 CCNE1 KO	Cancer cell line	Male
CVCL_B8TF	Abcam MCF-7 CCNE1 KO	Cancer cell line	Female
CVCL_B9EU	Abcam A-549 CCNE1 KO	Cancer cell line	Male
CVCL_JX63	MCF7EL	Cancer cell line	Female
CVCL_JX64	MCF7T1	Cancer cell line	Female
CVCL_JX65	MCF7T2	Cancer cell line	Female
CVCL_SH38	HAP1 CCNE1 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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