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Protein / target

DNA topoisomerase 2-alpha

Encoded byTOP2AP11388Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
17
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

ATP-dependent activity, acting on DNA

Strongest disease association

Neoplasms

Via encoding gene TOP2A · Clinical evidence · score 0.62

Therapeutic position

Established drug target

Small molecules and antibodies

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

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.

View complete UniProt function annotation

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

CytoplasmNucleus, nucleoplasmNucleusNucleus, nucleolus
Domains and Gene Ontology detail (35)

Domains & features

ToprimTopo IIA-type catalytic

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

1531 aa · 174 kDa · 4 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Transcriptional regulationUniProt · Reactome
View 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
View underlying pathways (2)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

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.

NUSAP1CDK1ASPMTOP1MKI67CCNB1BUB1CCNA2BUB1BCDC20TOP2A

10 strongest partners — larger node and heavier line mean higher confidence

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.

Approved medicines with mapped indications

1 medicine · 4 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Carcinoma, Small Cell1 medicine
Lung Neoplasms1 medicine
Small Cell Lung Carcinoma1 medicine
Broader indication categories (1)
Neoplasms1 medicine

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

17 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

3

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Etoposide
ApprovedInhibitor

DNA topoisomerase II inhibitor

Indicated for Carcinoma, Small Cell, Lung Neoplasms, Small Cell Lung Carcinoma, Neoplasms

Acts on a complex — shared with TOP2B · 1 of 2 recorded protein targets — narrow recorded profile

dexrazoxane
ApprovedInhibitor

DNA topoisomerase II inhibitor

Acts on a complex — shared with TOP2B · 1 of 2 recorded protein targets — narrow recorded profile

Becatecarin
Phase 3Inhibitor

DNA topoisomerase II inhibitor

Acts on a complex — shared with TOP2B · 1 of 3 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene TOP2A

Gene-level evidence surfaced through the gene TOP2Athat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Neoplasms
0.77Well supported

Clinical evidence dominant · Open Targets 0.62

Breast Neoplasms
0.76Well supported

Clinical evidence dominant · Open Targets 0.62

Leukemia, Myeloid, Acute
0.75Moderately supported

Clinical evidence dominant · Open Targets 0.61

Multiple Myeloma
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.59

Small Cell Lung Carcinoma
0.72Moderately supported

Clinical evidence dominant · Open Targets 0.58

View evidence synthesis (5)
NeoplasmsWell supported
0.77
agreement 0.610.92
Clinical83%Literature17%

Open Targets aggregate 0.62 · 2 independent evidence families

Breast NeoplasmsWell supported
0.76
agreement 0.610.92
Clinical84%Literature16%

Open Targets aggregate 0.62 · 2 independent evidence families

Leukemia, Myeloid, AcuteModerately supported
0.75
agreement 0.590.90
Clinical91%Literature9%

Open Targets aggregate 0.61 · 2 independent evidence families

Multiple MyelomaModerately supported
0.73
agreement 0.580.89
Clinical98%Literature2%

Open Targets aggregate 0.59 · 2 independent evidence families

Small Cell Lung CarcinomaModerately supported
0.72
agreement 0.570.88
Clinical88%Literature12%

Open Targets aggregate 0.58 · 2 independent evidence families

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 per-type scores above show the calculation.

Show all associations
Neoplasms0.62
Breast Neoplasms0.62
Leukemia, Myeloid, Acute0.61
Multiple Myeloma0.59
Small Cell Lung Carcinoma0.58
Sarcoma, Kaposi0.58
Hodgkin's Disease0.57
Ovarian Neoplasms0.55
Ovarian carcinoma0.55

Drug development

24 compounds recorded · 17 approved · 7 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 3 drugs that target this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
DEXRAZOXANEApproval
PAZUFLOXACINApproval
DOXORUBICINApproval
DOXORUBICIN HYDROCHLORIDEApproval
TENIPOSIDEApproval
MITOXANTRONE HYDROCHLORIDEApproval
BECATECARINPhase 3
ETOPOSIDE PHOSPHATEPhase 3
VALRUBICINApproval
VOSAROXINApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesStrong

Advanced Clinical support this modality.

Protein degradersEmerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (10)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · Advanced ClinicalPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

neutropeniaClinPGx

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

ACTIVE_NOT_RECRUITING · via Etoposide · NCT03533582

RECRUITING · via Etoposide · NCT01704716

ClinicalTrials.gov via the drug-target graph.

What's happening now

7

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Trial status changed2026-07-20

    A Phase II Trial of Tafasitamab and Lenalidomide Followed by Tafasitamab and ICE as Salvage Therapy for Transplant Eligible Patients With Relapsed/ Refractory Large B-Cell Lymphoma

    Status changed to Active, not recruiting · ClinicalTrials.gov · via Etoposide

  2. New publication2023-06-17
    Clinical insights into small cell lung cancer: Tumor heterogeneity, diagnosis, therapy, and future directions.

    CA: a cancer journal for clinicians · 2023 · 299 citations · Europe PMC · via Etoposide

  3. New publication2021-01-13
    Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133).

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021 · 649 citations · Europe PMC · via Etoposide

  4. New publication2018-09-25
    First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer.

    The New England journal of medicine · 2018 · 2,697 citations · Europe PMC · via Etoposide

  5. New publication2018-07-01
    As-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.

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018 · 27 citations · Europe PMC · via Etoposide

  6. Safety communication2014-12-11

    Drug Safety Update: Dexrazoxane (Cardioxane): restriction of use

    mhra · safety · mhra · via dexrazoxane

  7. New publication2002-01-01
    Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer.

    The New England journal of medicine · 2002 · 852 citations · Europe PMC · via Etoposide

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.