Protein / target
DNA topoisomerase 2-alpha
Protein at a glance
Biological role
ATP-dependent activity, acting on DNA
Strongest disease association
neoplasm
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
17 approved · 7 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand (PubMed:17567603, PubMed:18790802, PubMed:22013166, PubMed:22323612, PubMed:27754753). May play a role in regulating the period length of BMAL1 transcriptional oscillation (By similarity)
Subcellular location
Domains and Gene Ontology detail (35)Hide
Domains & features
Gene Ontology
- Cchromosome, centromeric region
- Ccondensed chromosome
- Ccytoplasm
- CDNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex
- Cnucleolus
- Cnucleoplasm
- Cnucleus
- Cprotein-containing complex
- Cribonucleoprotein complex
- FATP binding
- FATP-dependent activity, acting on DNA
- Fchromatin binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Transcriptional regulation
- ·Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA m…
- ·Transcription of E2F targets under negative control by DREAM complex
Kinase signalling
- ·protein kinase C binding
Apoptosis & cell death
- ·positive regulation of apoptotic process
View underlying pathways (2)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
DNA topoisomerase II inhibitor
Appears in clinical studies involving neoplasm, small cell lung carcinoma, lung cancer, small cell carcinoma
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 730 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 24 total
breast cancer · Hodgkins lymphoma · acute lymphoblastic leukemia
streptococcal pneumonia · Sepsis · legionellosis
Kaposi's sarcoma · breast neoplasm · plasma cell myeloma
bone sarcoma · urinary bladder carcinoma · breast cancer
neoplasm · acute lymphoblastic leukemia · hemophagocytic syndrome
multiple sclerosis · prostate cancer · acute myeloid leukemia
neuroblastoma · colorectal cancer · breast cancer
embryonal carcinoma · germinoma · nongerminomatous germ cell tumor
urinary bladder carcinoma · carcinoma · neoplasm
neoplasm · acute myeloid leukemia by FAB classification · acute myeloid leukemia
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- New publicationClinical insights into small cell lung cancer: Tumor heterogeneity, diagnosis, therapy, and future directions.
- New publicationUpdated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133).
- New publicationFirst-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer.
- New publicationAs-Needed Vs Immediate Etoposide Chemotherapy in Combination With Antiretroviral Therapy for Mild-to-Moderate AIDS-Associated Kaposi Sarcoma in Resource-Limited Settings: A5264/AMC-067 Randomized Clinical Trial.
- New publicationIrinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.