CDC25C

Summary

CDC25C (cell division cycle 25C, HGNC:1727) is a protein-coding gene on chromosome 5q31.2, encoding M-phase inducer phosphatase 3 (P30307). Functions as a dosage-dependent inducer in mitotic control.

This gene encodes a conserved protein that plays a key role in the regulation of cell division. The encoded protein directs dephosphorylation of cyclin B-bound CDC2 and triggers entry into mitosis. It also suppresses p53-induced growth arrest. Multiple alternatively spliced transcript variants of this gene have been described.

Source: NCBI Gene 995 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 89 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001790

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1727
Approved symbol	CDC25C
Name	cell division cycle 25C
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	PPP1R60
Ensembl gene	ENSG00000158402
Ensembl biotype	protein_coding
OMIM	157680
Entrez	995

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 26 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000323760, ENST00000415130, ENST00000503022, ENST00000504831, ENST00000510119, ENST00000513970, ENST00000514017, ENST00000514555, ENST00000648466, ENST00000875200, ENST00000875201, ENST00000920896, ENST00000920897, ENST00000920898, ENST00000920899, ENST00000920900, ENST00000920901, ENST00000920902, ENST00000920903, ENST00000920904, ENST00000920905, ENST00000920906, ENST00000920907, ENST00000920908, ENST00000920909, ENST00000920910, ENST00000920911, ENST00000920912

RefSeq mRNA: 8 — MANE Select: NM_001790 NM_001287582, NM_001287583, NM_001318098, NM_001364026, NM_001364027, NM_001364028, NM_001790, NM_022809

CCDS: CCDS4202, CCDS4203

Canonical transcript exons

ENST00000323760 — 14 exons

Exon	Start	End
ENSE00001086104	138290639	138290740
ENSE00001086106	138289501	138289563
ENSE00001086108	138286497	138286630
ENSE00001086111	138291970	138292116
ENSE00001086118	138329553	138329647
ENSE00001086119	138287169	138287267
ENSE00001086120	138326021	138326054
ENSE00001195280	138286022	138286133
ENSE00001245626	138319219	138319374
ENSE00001853000	138331595	138331804
ENSE00003638380	138330987	138331218
ENSE00003679308	138328484	138328529
ENSE00003785108	138325815	138325904
ENSE00003843850	138285269	138285841

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 88.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.3870 / max 100.8505, expressed in 1168 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63686	7.1593	1152
63685	0.1341	48
63688	0.0937	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.71	gold quality
ventricular zone	UBERON:0003053	86.85	gold quality
oocyte	CL:0000023	86.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.86	gold quality
secondary oocyte	CL:0000655	84.90	gold quality
left testis	UBERON:0004533	82.36	gold quality
ganglionic eminence	UBERON:0004023	82.33	gold quality
testis	UBERON:0000473	81.43	gold quality
right testis	UBERON:0004534	81.05	gold quality
embryo	UBERON:0000922	80.56	gold quality
sperm	CL:0000019	77.14	silver quality
male germ cell	CL:0000015	76.02	silver quality
endometrium epithelium	UBERON:0004811	74.21	gold quality
mucosa of transverse colon	UBERON:0004991	73.63	gold quality
stromal cell of endometrium	CL:0002255	72.94	gold quality
rectum	UBERON:0001052	72.86	gold quality
bone marrow	UBERON:0002371	69.61	gold quality
colonic epithelium	UBERON:0000397	66.06	silver quality
adult organism	UBERON:0007023	65.29	gold quality
adrenal tissue	UBERON:0018303	64.56	gold quality
vermiform appendix	UBERON:0001154	64.30	gold quality
trabecular bone tissue	UBERON:0002483	64.27	silver quality
esophagus mucosa	UBERON:0002469	64.13	gold quality
duodenum	UBERON:0002114	64.10	gold quality
thymus	UBERON:0002370	63.68	silver quality
lymph node	UBERON:0000029	63.46	gold quality
lower esophagus mucosa	UBERON:0035834	63.33	gold quality
bone marrow cell	CL:0002092	61.74	silver quality
granulocyte	CL:0000094	61.54	gold quality
jejunal mucosa	UBERON:0000399	61.35	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, DNMT1, E2F4, FOXM1, MTF1, MYC, NFYA, OLIG2, OTX2, SP1, SP3, TP53, TP63, TP73, ZHX2, ZNF331

miRNA regulators (miRDB)

25 targeting CDC25C, 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-4425	100.00	67.59	1049
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-3187-3P	97.38	65.80	904
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-6823-5P	96.26	65.69	919
HSA-MIR-6828-3P	96.06	67.61	1155
HSA-MIR-6858-5P	96.05	64.59	1020
HSA-MIR-4259	95.68	65.25	582
HSA-MIR-571	95.38	66.54	671

Literature-anchored findings (GeneRIF, showing 40)

• Analysis of cell cycle profile and cell cycle regulatory proteins indicated that arsenite arrested cell cycle at G(2)/M phase, partially through induction of cell division cycle 25 (Cdc25) isoform C (Cdc25C) degradation via ubiquitin-proteasome pathways (PMID:11842186)
• results suggest that Plk1 phosphorylates Cdc25C on Ser198 and regulates nuclear translocation of Cdc25C during prophase (PMID:11897663)
• role of degradation by oxidative stress in induction of cell cycle arrest (PMID:11925443)
• Human CDC25B and CDC25C differ by their ability to restore a functional checkpoint response after gene replacement in fission yeast (PMID:12099692)
• Ca2+ promotes erythrocyte band 3 tyrosine phosphorylation via dissociation of phosphotyrosine phosphatase from band 3. (PMID:12175337)
• phosphorylation by Chk2 (PMID:12386164)
• CDC25C is phosphorylated on Ser 214 during mitosis which, in turn, prevents phosphorylation of Ser 216. HeLa cells depeleted of endogenous CDC25C, when treated with exogenous CDC25C, had a substantial delay to mitotic entry. (PMID:12766774)
• cdc25C not only plays a role at the G2/M transition but also in the modulation of DNA replication (PMID:12857880)
• CDC25C translocation to the cell nucleus upon entry into mitosis is coordinated by Plk3 (PMID:14968113)
• binding to VPR protein in human cell lines correlates with G2 arrest (PMID:14972559)
• downregulation of Cdc25C is mediated by p53 via two independent mechanisms, one involving direct binding to the cdc25C promoter (PMID:15574328)
• Vpr promotes cell cycle arrest at the G(2)/M phase by facilitating association of 14-3-3 and Cdc25C (PMID:15708996)
• Vitamin C transiently arrests cancer cell cycle progression in S phase and G2/M boundary by modulating the kinetics of activation of CDC25C. (PMID:15887239)
• Data suggests that CDC25C might play an important role in prostate cancer progression and could be used to monitor and predict the aggressiveness of this disease. (PMID:16000564)
• Data suggest that Pim-1 activates Cdc25C by a direct phosphorylation and can thereby assume the function of a positive cell cycle regulator at the G2/M transition. (PMID:16356754)
• Crystallization experiments of PLK1 protein in complex with an unphosphorylated and a phosphorylated target peptide from Cdc25C yield crystals suitable for X-ray diffraction analysis. (PMID:16582488)
• These results demonstrate that the MAPK ERK signaling pathway contributes to the p53-independent antiproliferative functions of p14ARF. Furthermore, they identify a new mechanism by which phosphorylation at serine 216 participates to Cdc25C inactivation. (PMID:16582626)
• Phosphorylation of cdc25c can be used to test whether a pharmacologic inhibitor of Plk1 would exert the same cellular effects as interference with Plk1 on an mRNA level. (PMID:16648550)
• Chk1-mediated phosphorylation of Cdc25C plays a major role in response to LOR-mediated G(2)/M arrest. Although the Chk1-mediated cell growth arrest in a tumor cell line. (PMID:16649252)
• DNA damage-induced down-regulation of human Cdc25C (PMID:16807237)
• cdc25C is located in the cytoplasm at defined dense structures which by immunofluorescence analysis as well as by biochemical subfractionation turned out to be the Golgi apparatus. (PMID:17097061)
• In Lzts1(-/-) mouse embryo fibroblasts (MEFs), Cdc25C degradation was increased during M phase, resulting in decreased Cdk1 activity. (PMID:17349584)
• In A2780 cells, ERK1/2 interacts with Cdc25C in interphase and phosphorylates Cdc25C in mitosis. Inhibition of ERK activation partially inhibits T48 phosphorylation, Cdc25C activation, and mitotic induction. (PMID:17382881)
• Partial or complete loss of Lzts1 downregulates Cdc25C and inhibits Cdk1 activity during mitosis, leading to premature transition from metaphase to anaphase. (PMID:17419986)
• Cdc25C is located in the cytoplasm at defined dense structures, which according to immunofluorescence analysis, electron microscopy as well as biochemical subfractionation, are proven to be the centrosomes. (PMID:17548228)
• Cdc25B, but not Cdc25C, is capable of inhibiting cellular proliferation in a manner dependent upon its catalytic activity (PMID:17591782)
• p53 like other binding partners of cdc25C, regulates entry into mitosis by binding to cdc25C (PMID:17611691)
• PP2A:B56delta as a key upstream regulator of Cdk1 activity upon exit from mitosis (PMID:18056802)
• Cdc25C is a dual specificity phosphatase essential for dephosphorylation and activation of cyclin-dependent kinase is a prerequisite step for mitosis in all eucaryotes. Cdc25C activation requires phosphorylation. (PMID:18161793)
• both U(L)13 and U(S)3 viral kinases phosphorylate cdc25C and ICP22; however, in infected cells, the ability of cdc25C to activate cdc2 by dephosphorylation of the inactive cdc2 protein is reduced (PMID:18272572)
• cdc25C phosphatase plays a role in viral replication and that this role extends beyond its function of activating cdc2 for initiation of the ICP22-dependent cascade for upregulation of gamma(2) gene expression. (PMID:18272575)
• First-time evidence was provided for the existence of multiple species of Cdc25C in mitotic cell extracts. (PMID:18384749)
• Five novel splicing isoforms were detected, and the splicing patterns were generally distinct in neoplastic samples compared with healthy controls. (PMID:18464119)
• The expression of CDC25A, CDC25B and the proliferation marker Ki-67 are not associated with prognosis in LSCC (PMID:18551998)
• study reports that a fraction of Cdc25C localises to centrosomes in a cell cycle-dependent fashion, as of late S phase and throughout G2 and mitosis; data suggest an unexpected function for Cdc25C at the G2/M transition, in dephosphorylation of Cdk1 (PMID:18604163)
• Downregulation of the phosphatase CDC25A could solely be responsible for the slow growth phenotype in MCF10A/Bcl-2 cells. (PMID:18838868)
• Cdc25C has a role in sensitivity of tumor cells to doxorubicin-induced cell death (PMID:19074854)
• ectopic expression of PFKFB3 increased the expression of several key cell cycle proteins, including cyclin-dependent kinase (Cdk)-1, Cdc25C, and cyclin D3 and decreased the expression of the cell cycle inhibitor p27 (PMID:19473963)
• Adventitious arsenate reductase activity of the catalytic domain of the human and Cdc25C phosphatases (PMID:20025242)
• Cdc25 phosphatases are required for timely assembly of CDK1-cyclin B at the G2/M transition (PMID:20360007)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cdc25c	ENSMUSG00000044201
rattus_norvegicus	Cdc25c	ENSRNOG00000024008
caenorhabditis_elegans		WBGENE00000387
caenorhabditis_elegans		WBGENE00000388

Paralogs (2): CDC25B (ENSG00000101224), CDC25A (ENSG00000164045)

Protein

Protein identifiers

M-phase inducer phosphatase 3 — P30307 (reviewed: P30307)

Alternative names: Dual specificity phosphatase Cdc25C

All UniProt accessions (5): P30307, A0A3B3IT42, D6RD20, D6RJC2, H0Y999

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle. When phosphorylated, highly effective in activating G2 cells into prophase. Directly dephosphorylates CDK1 and activates its kinase activity.

Subunit / interactions. Interacts with MAPK14 and 14-3-3 proteins. When phosphorylated on Ser-129 and/or Thr-130, interacts with PLK1. Interacts with MARK3/C-TAK1. (Microbial infection) Interacts with HIV-1 Vpr; this interaction inactivates CDC25C phosphatase activity.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylated by CHEK1 and MAPK14 at Ser-216. This phosphorylation creates a binding site for 14-3-3 protein and inhibits the phosphatase. Phosphorylated by PLK4. Phosphorylated by PLK1, leading to activate the phosphatase activity. Phosphorylation by PLK3 at Ser-191 promotes nuclear translocation. Ser-198 is a minor phosphorylation site. Was initially reported to be phosphorylated by PLK3 at Ser-216. However, such phosphorylation by PLK3 was not confirmed by other groups. Phosphorylation at Thr-48, Thr-67, Ser-122, Thr-130, Ser-168 and Ser-214 occurs at G2 and G2-M transition and is probably catalyzed by CDK1. Ser-168 phosphorylation levels are lower than those at the other 5 CDK1 sites. Phosphorylation by CDK1 leads to increased activity.

Similarity. Belongs to the MPI phosphatase family.

Isoforms (5)

UniProt ID	Names	Canonical?
P30307-1	1, CDC25C1	yes
P30307-2	2, CDC25C2
P30307-5	3, CDC25C3
P30307-3	4, CDC25C4
P30307-4	5, CDC25C5, Cdc25Cdm

RefSeq proteins (8): NP_001274511, NP_001274512, NP_001305027, NP_001350955, NP_001350956, NP_001350957, NP_001781, NP_073720 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000751	MPI_Phosphatase	Family
IPR001763	Rhodanese-like_dom	Domain
IPR036873	Rhodanese-like_dom_sf	Homologous_superfamily

Pfam: PF00581, PF06617

Enzyme classification (BRENDA):

• EC 3.1.3.48 — protein-tyrosine-phosphatase (BRENDA: 59 organisms, 501 substrates, 1326 inhibitors, 270 Km, 165 kcat entries)

Substrate kinetics (BRENDA)

70 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-NITROPHENYL PHOSPHATE	0.0008–148	84
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.0039–0.862	27
P-NITROPHENYL PHOSPHATE	0.0024–10	20
DADEPYLIPQQG	0.0003–0.1	12
PHOSPHOTYROSINE	0.012–30	11
LYSOZYME	0.0003–0.012	5
MYELIN BASIC PROTEIN	0.0001–0.022	5
ACETYL-DADEPY-NH2	0.0228–0.219	4
ACETYL-DADEPYL-NH2	1.1–97.5	4
4,6,8-TRIMETHYL-2-OXO-2H-CHROMEN-7-YL DIHYDROGEN	0.02–0.156	3
SASASPYSASA	0.53–2.3	3
1-NAPHTHYL PHOSPHATE	1.19–1.88	2
3,6-FLUORESCEIN DIPHOSPHATE	15–19	2
4-METHYLUMBELLIFERYL PHOSPHATE	0.953–2.41	2
BOVINE SERUM ALBUMIN	0.0001–0.0003	2

Catalyzed reactions (Rhea), 1 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)

UniProt features (60 total): modified residue 19, mutagenesis site 10, strand 9, helix 6, sequence variant 4, region of interest 3, splice variant 2, turn 2, initiator methionine 1, chain 1, domain 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3BZI	X-RAY DIFFRACTION	2.1
5M37	X-RAY DIFFRACTION	2.35
5M35	X-RAY DIFFRACTION	2.38
5M36	X-RAY DIFFRACTION	2.45
3OP3	X-RAY DIFFRACTION	2.63
2OJX	X-RAY DIFFRACTION	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30307-F1	64.78	0.39

Functional residue map

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

Catalytic / active sites (1): 377

Post-translational modifications (19): 38, 48, 57, 61, 64, 67, 122, 129, 130, 168, 191, 198, 214, 216, 472, 61, 61, 2, 20

Mutagenesis-validated functional residues (10):

Position	Phenotype
129	loss of phosphorylation. severely impairs plk1-binding.
130	loss of phosphorylation. severely impairs plk1-binding.
191	facilitates nuclear exclusion.
191	mimicks phosphorylation state, leading to enhanced accumulation in the nucleus.
211	reduces phosphorylation by mark3 and chek1.
216	no effect on interaction with mark3. abolishes phosphorylation by mark3.
221	abolishes interaction with mark3. reduces phosphorylation of s-216 by mark3.
242–244	no effect on interaction with mark3.
352	partial loss of hiv-1 vpr binding.
359	no effect on hiv-1 vpr binding.

Function

Pathways and Gene Ontology

Reactome pathways

28 pathways

ID	Pathway
R-HSA-156711	Polo-like kinase mediated events
R-HSA-176187	Activation of ATR in response to replication stress
R-HSA-5625740	RHO GTPases activate PKNs
R-HSA-6804114	TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest
R-HSA-6804115	TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-75035	Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
R-HSA-8862803	Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-6791312	TP53 Regulates Transcription of Cell Cycle Genes
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-69481	G2/M Checkpoints
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8863678	Neurodegenerative Diseases
R-HSA-9645723	Diseases of programmed cell death
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3
R-HSA-9734009	Defective Intrinsic Pathway for Apoptosis

MSigDB gene sets: 351 (showing top): GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_NUCLEAR_DIVISION, PAL_PRMT5_TARGETS_UP, CROONQUIST_NRAS_SIGNALING_DN, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, BIOCARTA_SRCRPTP_PATHWAY, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, REACTOME_ACTIVATION_OF_ATR_IN_RESPONSE_TO_REPLICATION_STRESS, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2, MODULE_308, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE, GOLDRATH_ANTIGEN_RESPONSE

GO Biological Process (9): regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0000079), G2/M transition of mitotic cell cycle (GO:0000086), regulation of mitotic nuclear division (GO:0007088), cell population proliferation (GO:0008283), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), cell division (GO:0051301), positive regulation of G2/MI transition of meiotic cell cycle (GO:0110032), protein dephosphorylation (GO:0006470), positive regulation of cell cycle G2/M phase transition (GO:1902751)

GO Molecular Function (7): phosphoprotein phosphatase activity (GO:0004721), protein tyrosine phosphatase activity (GO:0004725), protein kinase binding (GO:0019901), WW domain binding (GO:0050699), protein serine/threonine kinase binding (GO:0120283), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrial intermembrane space (GO:0005758), cytosol (GO:0005829), nuclear speck (GO:0016607)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
G2/M Transition	2
G2/M Checkpoints	2
TP53 Regulates Transcription of Cell Cycle Genes	2
RHO GTPase Effectors	1
G2/M DNA damage checkpoint	1
Neurodegenerative Diseases	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Cell Cycle, Mitotic	1
Transcriptional Regulation by TP53	1
Mitotic G2-G2/M phases	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell cycle G2/M phase transition	2
cellular process	2
positive regulation of cell cycle G2/M phase transition	2
cyclin-dependent protein serine/threonine kinase activity	1
regulation of protein serine/threonine kinase activity	1
mitotic cell cycle	1
mitotic cell cycle phase transition	1
regulation of mitotic cell cycle	1
regulation of cell cycle process	1
regulation of nuclear division	1
mitotic nuclear division	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
G2/MI transition of meiotic cell cycle	1
regulation of G2/MI transition of meiotic cell cycle	1
positive regulation of meiotic cell cycle phase transition	1
dephosphorylation	1
protein modification process	1
positive regulation of cell cycle phase transition	1
regulation of cell cycle G2/M phase transition	1
phosphatase activity	1
catalytic activity, acting on a protein	1
phosphoprotein phosphatase activity	1
kinase binding	1
protein domain specific binding	1
protein kinase binding	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
mitochondrial envelope	1
organelle envelope lumen	1
cytoplasm	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

2400 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC25C	CDK1	P06493	976
CDC25C	YWHAE	P29360	969
CDC25C	CCNB1	P14635	951
CDC25C	PLK1	P53350	951
CDC25C	CHEK1	O14757	939
CDC25C	CHEK2	O96017	919
CDC25C	WEE1	P30291	894
CDC25C	SFN	P31947	883
CDC25C	CDK2	P24941	816
CDC25C	ATM	Q13315	807
CDC25C	MARK3	P27448	802
CDC25C	YWHAZ	P29213	795
CDC25C	TP53	P04637	791
CDC25C	PLK3	Q9H4B4	783
CDC25C	CDC20	Q12834	757

IntAct

109 interactions, top by confidence:

A	B	Type	Score
CDC25C	YWHAB	psi-mi:“MI:0915”(physical association)	0.890
PLK1	CDC25C	psi-mi:“MI:0407”(direct interaction)	0.860
PLK1	CDC25C	psi-mi:“MI:0915”(physical association)	0.860
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
CDC25C	YWHAE	psi-mi:“MI:0915”(physical association)	0.770
YWHAE	CDC25C	psi-mi:“MI:0914”(association)	0.770
YWHAB	WDR62	psi-mi:“MI:0914”(association)	0.770
YWHAZ	CDC25C	psi-mi:“MI:0915”(physical association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
CDC25C	CDK1	psi-mi:“MI:0914”(association)	0.620
CDK1	CDC25C	psi-mi:“MI:0915”(physical association)	0.620
CDC25C	CHEK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.620
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
PPP2R5D	CDC25C	psi-mi:“MI:0915”(physical association)	0.590
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
EGFR	CDC25C	psi-mi:“MI:0915”(physical association)	0.550
CDC25C	EGFR	psi-mi:“MI:0915”(physical association)	0.550
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAE	SHTN1	psi-mi:“MI:0914”(association)	0.530

BioGRID (298): HSP90AA1 (Affinity Capture-Western), CDC37 (Affinity Capture-Western), HSPA4 (Affinity Capture-Western), CDC25C (Two-hybrid), CDC25C (Biochemical Activity), CDC25C (Affinity Capture-MS), CDC25C (Proximity Label-MS), CDC25C (PCA), CDC25C (Affinity Capture-Luminescence), CDC25C (Biochemical Activity), CDC25C (Biochemical Activity), CCNB2 (Affinity Capture-MS), CDK1 (Affinity Capture-MS), FAM27E3 (Affinity Capture-MS), SUFU (Affinity Capture-MS)

ESM2 similar proteins: A0JM98, A1L1H3, A4IGY9, A5D7P0, A5PLL1, A7MBD1, B2RWW0, D3ZF42, O75113, O88866, P12525, P30304, P30305, P30306, P30307, P30308, P30309, P30310, P30311, P48964, P48965, P48966, P48967, P48968, P57058, Q29029, Q4G163, Q56NI9, Q5QJC4, Q5SW75, Q66JT0, Q68UT7, Q6GQJ2, Q6IE82, Q6P1H6, Q6PCM1, Q6PJP8, Q6S7F2, Q6YI93, Q76I76

Diamond homologs: A5D7P0, A7MBD1, O44552, O44628, P06652, P20483, P23748, P30303, P30304, P30305, P30306, P30307, P30308, P30309, P30310, P30311, P30634, P48964, P48965, P48966, P48967, P48968, Q03019, Q29029, Q54QM6, Q8WZK3, P54510

SIGNOR signaling

56 interactions.

A	Effect	B	Mechanism
CHEK2	“down-regulates activity”	CDC25C	phosphorylation
BRSK1	“down-regulates activity”	CDC25C	phosphorylation
p38	“down-regulates activity”	CDC25C	phosphorylation
PLK1	up-regulates	CDC25C	phosphorylation
PPP1CA	up-regulates	CDC25C	binding
PLK3	up-regulates	CDC25C	phosphorylation
CSNK2A1	down-regulates	CDC25C	phosphorylation
ROBO	down-regulates	CDC25C	phosphorylation
CHEK1	“down-regulates quantity by destabilization”	CDC25C	phosphorylation
YWHAQ	down-regulates	CDC25C	relocalization
MAPK10	down-regulates	CDC25C	phosphorylation
MAPK8	down-regulates	CDC25C	phosphorylation
MAPK9	down-regulates	CDC25C	phosphorylation
CDK2	up-regulates	CDC25C	phosphorylation
CDC25C	up-regulates	CDK1	dephosphorylation
CyclinE/CDK2	up-regulates	CDC25C	phosphorylation
CyclinB/CDK1	up-regulates	CDC25C	phosphorylation
PKN1	unknown	CDC25C	phosphorylation
CDC25C	“up-regulates activity”	CyclinB/CDK1	dephosphorylation
CyclinB/CDK1	“up-regulates activity”	CDC25C	phosphorylation
PP1	up-regulates	CDC25C	binding
JNK	down-regulates	CDC25C	phosphorylation
CDC25C	“up-regulates activity”	CDK1	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	9	99.1×	2e-14
Activation of BAD and translocation to mitochondria	7	87.4×	9e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	77.1×	1e-10
Activation of BH3-only proteins	7	57.0×	1e-09
RHO GTPases activate PKNs	7	36.4×	3e-08
Intrinsic Pathway for Apoptosis	7	33.6×	5e-08
FOXO-mediated transcription	5	27.5×	2e-05
Translocation of SLC2A4 (GLUT4) to the plasma membrane	8	20.2×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	26.8×	3e-05
epidermal growth factor receptor signaling pathway	5	15.1×	3e-03
intracellular protein localization	9	11.5×	3e-05
protein phosphorylation	9	7.5×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2292 predictions. Top by Δscore:

Variant	Effect	Δscore
5:138286492:CTCA:C	donor_loss	1.0000
5:138286493:TCA:T	donor_loss	1.0000
5:138286494:CAC:C	donor_loss	1.0000
5:138286495:A:AC	donor_gain	1.0000
5:138286496:C:CT	donor_gain	1.0000
5:138286496:CA:C	donor_gain	1.0000
5:138286496:CATT:C	donor_gain	1.0000
5:138286627:CTCC:C	acceptor_gain	1.0000
5:138286629:CC:C	acceptor_gain	1.0000
5:138286629:CCCTG:C	acceptor_loss	1.0000
5:138286630:CC:C	acceptor_gain	1.0000
5:138286630:CCTGT:C	acceptor_loss	1.0000
5:138289499:A:AC	donor_gain	1.0000
5:138289500:C:CC	donor_gain	1.0000
5:138319215:TTA:T	donor_loss	1.0000
5:138319218:C:CT	donor_loss	1.0000
5:138319370:TTGTC:T	acceptor_gain	1.0000
5:138319371:TGTCC:T	acceptor_loss	1.0000
5:138319372:GTCC:G	acceptor_loss	1.0000
5:138319374:CCTGT:C	acceptor_loss	1.0000
5:138319375:C:CA	acceptor_loss	1.0000
5:138319376:T:C	acceptor_loss	1.0000
5:138328482:A:AC	donor_gain	1.0000
5:138328482:ACAT:A	donor_gain	1.0000
5:138328482:ACATC:A	donor_gain	1.0000
5:138328483:C:CC	donor_gain	1.0000
5:138328483:CAT:C	donor_gain	1.0000
5:138328483:CATC:C	donor_gain	1.0000
5:138328483:CATCC:C	donor_gain	1.0000
5:138328485:T:TA	donor_gain	1.0000

AlphaMissense

3120 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:138286520:G:C	F379L	0.998
5:138286520:G:T	F379L	0.998
5:138286522:A:G	F379L	0.998
5:138286111:C:G	D395H	0.997
5:138287204:G:C	R331G	0.997
5:138287204:G:T	R331S	0.997
5:138287190:C:A	E335D	0.996
5:138287190:C:G	E335D	0.996
5:138287203:C:G	R331P	0.996
5:138287205:A:C	C330W	0.995
5:138286120:G:T	R392S	0.994
5:138287179:C:T	G339E	0.994
5:138287203:C:A	R331L	0.994
5:138286119:C:G	R392P	0.993
5:138286528:A:G	C377R	0.993
5:138287173:A:T	I341N	0.993
5:138287191:T:A	E335V	0.993
5:138286048:A:C	Y416D	0.992
5:138286059:A:G	L412P	0.992
5:138286078:A:C	Y406D	0.992
5:138286106:C:A	R396S	0.992
5:138286106:C:G	R396S	0.992
5:138286526:A:C	C377W	0.992
5:138286527:C:T	C377Y	0.992
5:138286533:A:G	F375S	0.992
5:138287189:A:C	Y336D	0.992
5:138287207:A:G	C330R	0.992
5:138287209:T:G	D329A	0.992
5:138287210:C:G	D329H	0.992
5:138286068:A:G	L409P	0.991

dbSNP variants (sampled 300 via entrez): RS1000105508 (5:138303572 C>T), RS1000142993 (5:138291107 A>G), RS1000162414 (5:138320030 G>A), RS1000169474 (5:138289888 G>A,C), RS1000173148 (5:138321107 G>A), RS1000182064 (5:138310310 T>A,C), RS1000198298 (5:138310556 T>A), RS1000292168 (5:138302686 C>G,T), RS1000366557 (5:138305192 T>A), RS1000372338 (5:138317408 G>A,T), RS1000379215 (5:138287782 A>G), RS1000431470 (5:138338096 C>A,T), RS1000491532 (5:138314924 A>C), RS1000502647 (5:138318229 C>T), RS1000569687 (5:138324599 A>C)

Disease associations

OMIM: gene MIM:157680 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002539_60	Schizophrenia	5.000000e-09
GCST003582_1	Response to radiotherapy in prostate cancer (toxicity, urinary frequency)	4.000000e-08
GCST004521_66	Autism spectrum disorder or schizophrenia	1.000000e-08
GCST007450_4	Normal facial asymmetry (deformation magnitude)	5.000000e-06
GCST008103_73	Bipolar disorder	8.000000e-07
GCST008115_23	Bipolar I disorder	2.000000e-07
GCST009725_84	Intraocular pressure	5.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009751	facial asymmetry measurement
EFO:0009963	bipolar I disorder
EFO:0004695	intraocular pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2378 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 21,034 (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
CHEMBL590	MENADIONE	4	21,034
CHEMBL85943	SODIUM TUNGSTATE	2

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

ChEMBL bioactivities

72 potent at pChembl≥5 of 123 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.64	IC50	23	nM	CHEMBL5271462
7.64	IC50	23	nM	CHEMBL5288122
7.25	IC50	56.9	nM	CHEMBL429095
7.22	IC50	60	nM	CHEMBL5423941
7.22	IC50	60	nM	CHEMBL5560222
7.11	IC50	78	nM	CHEMBL429095
7.05	IC50	90	nM	CHEMBL4521092
7.05	Ki	89	nM	CHEMBL337173
7.00	IC50	100	nM	CHEMBL4093222
6.89	IC50	130	nM	CHEMBL199359
6.89	IC50	130	nM	CHEMBL382593
6.82	IC50	150	nM	CHEMBL373195
6.77	IC50	170	nM	CHEMBL1765351
6.68	IC50	210	nM	CHEMBL4566962
6.64	IC50	230	nM	CHEMBL199360
6.64	IC50	230	nM	CHEMBL200805
6.60	IC50	250	nM	CHEMBL337173
6.52	IC50	300	nM	CHEMBL4066424
6.40	IC50	400	nM	CHEMBL4085485
6.40	Ki	400	nM	CHEMBL4570006
6.38	IC50	420	nM	CHEMBL4466461
6.19	Ki	640	nM	CHEMBL314400
6.16	IC50	690	nM	CHEMBL4060132
6.12	IC50	760	nM	CHEMBL337173
6.11	IC50	770	nM	CHEMBL4097725
6.10	IC50	800	nM	CHEMBL4086414
6.05	IC50	900	nM	CHEMBL3623325
6.01	IC50	980	nM	CHEMBL4066643
6.00	IC50	1000	nM	CHEMBL4094178
5.84	IC50	1440	nM	CHEMBL4075821
5.76	IC50	1720	nM	CHEMBL5278031
5.72	Ki	1900	nM	CHEMBL4447602
5.70	IC50	2000	nM	CHEMBL5284545
5.64	IC50	2270	nM	CHEMBL200117
5.64	IC50	2300	nM	CHEMBL4098262
5.60	IC50	2510	nM	CHEMBL5269565
5.59	IC50	2550	nM	CHEMBL5269423
5.46	IC50	3500	nM	CHEMBL1967787
5.46	IC50	3500	nM	CHEMBL87763
5.46	IC50	3500	nM	CHEMBL314400
5.44	IC50	3640	nM	CHEMBL4105005
5.41	IC50	3900	nM	CHEMBL186631
5.40	IC50	4000	nM	CHEMBL186644
5.40	Ki	4000	nM	CHEMBL4442406
5.37	IC50	4300	nM	CHEMBL228419
5.36	IC50	4370	nM	CHEMBL4097300
5.35	IC50	4460	nM	CHEMBL4066281
5.33	IC50	4670	nM	CHEMBL4094844
5.32	IC50	4780	nM	SHIKONIN
5.30	IC50	5000	nM	CHEMBL1327816

PubChem BioAssay actives

66 with measured affinity, of 262 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
5-[2-(dimethylamino)ethylamino]-2-methyl-1,3-benzothiazole-4,7-dione	1942250: Inhibition of recombinant CDC25C (unknown origin)	ic50	0.0230	uM
2-(2,5-difluorophenyl)-6-[2-(dimethylamino)ethylamino]-1,3-benzoxazole-4,7-dione	1942250: Inhibition of recombinant CDC25C (unknown origin)	ic50	0.0230	uM
2,3-bis(2-hydroxyethylsulfanyl)naphthalene-1,4-dione	593357: Inhibition of human Cdc25C	ic50	0.0569	uM
6-chloro-7-[1-[1-[4-(hydroxymethyl)phenyl]triazol-4-yl]ethylamino]quinoline-5,8-dione	2009523: Inhibition of full-length recombinant human CDC25C using OMFP as substrate incubated for 5 to 8 mins by fluorescence based assay	ic50	0.0600	uM
6-chloro-7-[1-[1-[[4-(hydroxymethyl)phenyl]methyl]triazol-4-yl]ethylamino]quinoline-5,8-dione	2067126: Inhibition of full-length recombinant human CDC25C incubated for 5 to 8 mins by fluorescence based assay	ic50	0.0600	uM
6-chloro-7-(2-morpholin-4-ylethylamino)quinoline-5,8-dione	593357: Inhibition of human Cdc25C	ki	0.0890	uM
6-chloro-7-[[1-[(4-methylphenyl)methyl]triazol-4-yl]methylamino]quinoline-5,8-dione	1517347: Inhibition of recombinant human Cdc25C using OMFP as substrate preincubated for 5 to 8 mins and measured every 5 mins 60 mins by fluorescence based assay	ic50	0.0900	uM
12-oxapentacyclo[12.8.0.02,11.05,10.015,20]docosa-1(14),2(11),3,5,7,9,15(20),17,21-nonaene-13,16,19-trione	1452404: Inhibition of recombinant human full length GST-tagged CDC25C expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	0.1000	uM
5-[2-(dimethylamino)ethylamino]-2-ethyl-1,3-benzoxazole-4,7-dione	258633: Inhibitory activity against recombinant CDC25C	ic50	0.1300	uM
6-[2-(dimethylamino)ethylamino]-2-ethyl-1,3-benzoxazole-4,7-dione	258633: Inhibitory activity against recombinant CDC25C	ic50	0.1300	uM
5-[2-(dimethylamino)ethylamino]-2,6-dimethyl-1,3-benzothiazole-4,7-dione	593357: Inhibition of human Cdc25C	ic50	0.1700	uM
3-[[4-[[(6-chloro-5,8-dioxoquinolin-7-yl)amino]methyl]triazol-1-yl]methyl]benzonitrile	1517347: Inhibition of recombinant human Cdc25C using OMFP as substrate preincubated for 5 to 8 mins and measured every 5 mins 60 mins by fluorescence based assay	ic50	0.2100	uM
5-[2-(dimethylamino)ethylamino]-2-phenyl-1,3-benzoxazole-4,7-dione	258633: Inhibitory activity against recombinant CDC25C	ic50	0.2300	uM
6-[2-(dimethylamino)ethylamino]-2-phenyl-1,3-benzoxazole-4,7-dione	258633: Inhibitory activity against recombinant CDC25C	ic50	0.2300	uM
8-(diethylamino)naphtho[1,2-c]chromene-1,4,5-trione	1452404: Inhibition of recombinant human full length GST-tagged CDC25C expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	0.3000	uM
ethyl 2-(naphthalen-1-ylamino)benzoate	1516497: Inhibition of N-terminal His6-tagged human CDC25C (280 to 454 residues) expressed in Escherichia coli BL21(DE3) cells using OMFP as substrate by double reciprocal Lineweaver-Burk plot analysis	ki	0.4000	uM
9-fluoronaphtho[1,2-c]chromene-1,4,5-trione	1452404: Inhibition of recombinant human full length GST-tagged CDC25C expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	0.4000	uM
2-[[4-[[(6-chloro-5,8-dioxoquinolin-7-yl)amino]methyl]triazol-1-yl]methyl]benzonitrile	1517347: Inhibition of recombinant human Cdc25C using OMFP as substrate preincubated for 5 to 8 mins and measured every 5 mins 60 mins by fluorescence based assay	ic50	0.4200	uM
2,5-dihydroxy-3-[7-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl]-1H-indol-3-yl]cyclohexa-2,5-diene-1,4-dione	51732: Inhibitory constant of compound against Cell division cycle 25 was determined	ki	0.6400	uM
8-fluoronaphtho[1,2-c]chromene-1,4,5-trione	1452404: Inhibition of recombinant human full length GST-tagged CDC25C expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	0.6900	uM
8-chloronaphtho[1,2-c]chromene-1,4,5-trione	1452404: Inhibition of recombinant human full length GST-tagged CDC25C expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	0.7700	uM
8-hydroxynaphtho[1,2-c]chromene-1,4,5-trione	1452404: Inhibition of recombinant human full length GST-tagged CDC25C expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	0.8000	uM
2-[(7-methoxy-2-oxochromen-4-yl)methylsulfanyl]naphthalene-1,4-dione	1942258: Inhibition of recombinant N-terminal GST-tagged CDC25C (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 2 hrs	ic50	0.9000	uM
8-methoxynaphtho[1,2-c]chromene-1,4,5-trione	1452404: Inhibition of recombinant human full length GST-tagged CDC25C expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	0.9800	uM
8-methylnaphtho[1,2-c]chromene-1,4,5-trione	1452404: Inhibition of recombinant human full length GST-tagged CDC25C expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	1.0000	uM
9-chloronaphtho[1,2-c]chromene-1,4,5-trione	1452404: Inhibition of recombinant human full length GST-tagged CDC25C expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	1.4400	uM
7-(furan-2-yl)-5-propan-2-ylindeno[1,2-b]indole-6,9,10-trione	1942243: Inhibition of CDC25C (unknown origin)	ic50	1.7200	uM
ethyl 3-[(3-methoxynaphthalen-1-yl)amino]benzoate	1516497: Inhibition of N-terminal His6-tagged human CDC25C (280 to 454 residues) expressed in Escherichia coli BL21(DE3) cells using OMFP as substrate by double reciprocal Lineweaver-Burk plot analysis	ki	1.9000	uM
7-phenyl-5-propan-2-ylindeno[1,2-b]indole-6,9,10-trione	1942243: Inhibition of CDC25C (unknown origin)	ic50	2.0000	uM
2-[4-[7-(4-tetradecylbenzoyl)cyclopenta[d]oxazin-4-yl]phenoxy]acetic acid	259933: Inhibitory activity against cdc25C phosphatase	ic50	2.2700	uM
naphtho[1,2-c]chromene-1,4,5-trione	1452404: Inhibition of recombinant human full length GST-tagged CDC25C expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	2.3000	uM
8-methyl-5-propan-2-ylindeno[1,2-b]indole-6,9,10-trione	1942243: Inhibition of CDC25C (unknown origin)	ic50	2.5100	uM
7-(4-fluorophenyl)-5-propan-2-ylindeno[1,2-b]indole-6,9,10-trione	1942243: Inhibition of CDC25C (unknown origin)	ic50	2.5500	uM
2,5-dihydroxy-3-[7-[(2-methylphenyl)methyl]-1H-indol-3-yl]cyclohexa-2,5-diene-1,4-dione	52045: Eight point inhibitory concentration against Cell division cycle 25 degree C was determined	ic50	3.5000	uM
2-(3-hydroxy-6-oxoxanthen-9-yl)cyclohexane-1-carboxylic acid	1942243: Inhibition of CDC25C (unknown origin)	ic50	3.5000	uM
6H-benzo[i]phenanthridine-1,4,5-trione	1452404: Inhibition of recombinant human full length GST-tagged CDC25C expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	3.6400	uM
4-(dimethylamino)-2-[[2-(4-nitrophenyl)ethylamino]methyl]phenol	241770: Inhibitory concentration for human cell division cycle 25 degree C phosphatase	ic50	3.9000	uM
4-(dimethylamino)-2-methoxy-6-[[2-(4-nitrophenyl)ethylamino]methyl]phenol	241770: Inhibitory concentration for human cell division cycle 25 degree C phosphatase	ic50	4.0000	uM
3-[(5-aminonaphthalen-1-yl)amino]benzoic acid	1516497: Inhibition of N-terminal His6-tagged human CDC25C (280 to 454 residues) expressed in Escherichia coli BL21(DE3) cells using OMFP as substrate by double reciprocal Lineweaver-Burk plot analysis	ki	4.0000	uM
3-(4-heptadecyl-2,5-dioxofuran-3-yl)propanoic acid	287161: Inhibition of human GST-Cdc25C expressed in Escherichia coli BL21(DE3)	ic50	4.3000	uM
12-azapentacyclo[12.8.0.02,11.05,10.015,20]docosa-1(14),2(11),3,5,7,9,15(20),17,21-nonaene-13,16,19-trione	1452404: Inhibition of recombinant human full length GST-tagged CDC25C expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	4.3700	uM
8-fluoro-6H-benzo[i]phenanthridine-1,4,5-trione	1452404: Inhibition of recombinant human full length GST-tagged CDC25C expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	4.4600	uM
9-fluoro-6H-benzo[i]phenanthridine-1,4,5-trione	1452404: Inhibition of recombinant human full length GST-tagged CDC25C expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	4.6700	uM
5,8-dihydroxy-2-[(1R)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione	1942260: Inhibition of human recombinant CDC25C	ic50	4.7800	uM
3-methoxy-N,N,4-trimethyl-5-[[methyl-[2-(4-nitrophenyl)ethyl]amino]methyl]aniline	241770: Inhibitory concentration for human cell division cycle 25 degree C phosphatase	ic50	5.4000	uM
4-[(3-chloro-1,4-dioxonaphthalen-2-yl)amino]benzoic acid	1942254: Inhibition of human CDC25C	ic50	5.4100	uM
8-chloro-6H-benzo[i]phenanthridine-1,4,5-trione	1452404: Inhibition of recombinant human full length GST-tagged CDC25C expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	5.5000	uM
4-(dimethylamino)-2-[[methyl-[2-(4-nitrophenyl)ethyl]amino]methyl]phenol	241770: Inhibitory concentration for human cell division cycle 25 degree C phosphatase	ic50	5.6000	uM
3-(2,5-dioxo-4-tridecylfuran-3-yl)propanoic acid	287161: Inhibition of human GST-Cdc25C expressed in Escherichia coli BL21(DE3)	ic50	5.7000	uM
2-methoxy-6-[(S)-(4-methylphenyl)sulfinyl]cyclohexa-2,5-diene-1,4-dione	1942254: Inhibition of human CDC25C	ic50	5.7200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
ON 01910	decreases expression, decreases phosphorylation, increases phosphorylation, affects cotreatment	5
Paclitaxel	increases phosphorylation, affects reaction, decreases phosphorylation, decreases expression, affects cotreatment (+3 more)	5
ochratoxin A	decreases expression, decreases reaction, affects cotreatment, increases reaction	4
diallyl trisulfide	decreases expression, increases phosphorylation, increases degradation, decreases reaction	4
Doxorubicin	decreases activity, decreases reaction, increases expression, increases phosphorylation, increases response to substance (+1 more)	4
Quercetin	decreases expression, increases phosphorylation	4
bisphenol A	decreases expression, increases phosphorylation, affects cotreatment, increases expression	3
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	decreases expression, increases expression	3
Arsenic Trioxide	decreases expression, increases reaction, affects cotreatment, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	3
Valproic Acid	affects expression, decreases expression	3
alpha-naphthoflavone	decreases expression, decreases reaction, increases phosphorylation	2
norcantharidin	decreases expression, increases reaction	2
tanespimycin	affects cotreatment, decreases expression	2
(+)-JQ1 compound	affects cotreatment, decreases expression	2
Resveratrol	decreases reaction, increases phosphorylation, affects cotreatment, increases expression, increases activity	2
Caffeine	affects binding, decreases reaction, increases phosphorylation, decreases expression	2
Estradiol	decreases expression, increases expression	2
Hydrogen Peroxide	affects expression, decreases expression	2
Tetrachlorodibenzodioxin	increases reaction, affects expression, decreases reaction, increases phosphorylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
Lithium Chloride	increases expression, decreases expression	2
3-methoxy-6-(((2,4,6-trimethoxystyryl)sulfonyl)methyl)pyridin-2-amine	decreases expression	1
ziyuglycoside II	decreases expression, increases phosphorylation	1
LL202 flavonoid	decreases expression	1
scutebarbatine A	decreases phosphorylation	1
NVP-BHG712	affects cotreatment, decreases expression	1
FR900359	increases phosphorylation	1

ChEMBL screening assays

56 unique, capped per target: 56 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1260114	Binding	Inhibition of human recombinant GST-tagged CDC25C expressed in bacterial expression system at 100 uM after 2 hrs	Synthesis and biological evaluation of novel coumarin-based inhibitors of Cdc25 phosphatases. — 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_B1MV	Abcam HeLa CDC25C KO	Cancer cell line	Female
CVCL_SI02	HAP1 CDC25C (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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