Protein / target

DNA topoisomerase 2-beta

TOP2BQ02880Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
7
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Ribonucleoprotein complex binding

Strongest disease association

B-cell immunodeficiency, distal limb anomalies, and urogenital malformations

Genetic evidence · score 0.83

Therapeutic maturity

Clinically validated target

7 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

7 approved · 4 in clinical development

30 linked trials

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

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. Plays a role in B-cell differentiation

Subcellular location

Nucleus, nucleolusNucleus, nucleoplasmNucleus
Domains and Gene Ontology detail (22)

Domains & features

ToprimTopo IIA-type catalytic

Gene Ontology

  • Ccytosol
  • Cnucleolus
  • Cnucleoplasm
  • Cnucleus
  • Cribonucleoprotein complex
  • FATP binding
  • Fchromatin binding
  • FDNA binding
  • FDNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity
  • Fmetal ion binding
  • Fribonucleoprotein complex binding
  • PB cell differentiation

1626 aa · 183 kDa · 2 isoforms

Biological roles

Reactome v97

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

Immune signallingGO
View supporting evidence

Immune signalling

  • ·B cell differentiation
View underlying pathways (1)

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.

TOP1TOP2ATOP1MTTOPBP1TDP2SMC2CTCFARUBE2IKCTD9TOP2B

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.

Drugs targeting this protein

1

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.

Etoposide
ApprovedInhibitor

DNA topoisomerase II inhibitor

Appears in clinical studies involving neoplasm, small cell lung carcinoma, lung cancer, small cell carcinoma

Acts on a complex — shared with TOP2A · 1 of 2 recorded protein targets — narrow recorded profile

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

B-cell immunodeficiency, distal limb anomalies, and urogenital malformations0.83

Genetic · overall 0.72

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

neoplasm0.95

Clinical · overall 0.58

small cell lung carcinoma0.92

Clinical · overall 0.56

breast cancer0.90

Clinical · overall 0.55

small cell carcinoma0.80

Clinical · overall 0.49

cardiomyopathy0.76

Clinical · overall 0.47

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

acute myeloid leukemia0.44

Clinical

neuroblastoma0.43

Clinical

acute lymphoblastic leukemia0.42

Clinical

neurodegenerative disease0.42

Pathway

Show all associations
B-cell immunodeficiency, distal limb anomalies, and urogenital malformations0.72
neoplasm0.58
small cell lung carcinoma0.56
breast cancer0.55
small cell carcinoma0.49
cardiomyopathy0.47
acute myeloid leukemia0.44
neuroblastoma0.43
acute lymphoblastic leukemia0.42
neurodegenerative disease0.42

Open Targets ranks 731 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 · 11 total

DEXRAZOXANE HYDROCHLORIDEApproval

breast cancer · cardiomyopathy · Hodgkins lymphoma

ETOPOSIDEApproval

neoplasm · small cell lung carcinoma · lung cancer

C-1311Phase 2

breast cancer

BECATECARINPhase 3

neuroblastoma · colorectal cancer · breast cancer

TENIPOSIDEApproval

neoplasm · acute lymphoblastic leukemia · hemophagocytic syndrome

AMSACRINEApproval

neoplasm · acute myeloid leukemia · acute myeloid leukemia

BERUBICINPhase 2

glioblastoma

PAZUFLOXACINApproval

streptococcal pneumonia · Sepsis · legionellosis

VOSAROXINApproval

neoplasm · acute myeloid leukemia by FAB classification · acute myeloid leukemia

BERUBICIN HYDROCHLORIDEPhase 2

breast cancer · glioblastoma · anaplastic astrocytoma

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

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.

Show remaining trials (24)

ACTIVE_NOT_RECRUITING · via Etoposide · NCT03020030

COMPLETED · via Etoposide · NCT00426101

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

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.

B-cell immunodeficiency, distal limb anomalies, and urogenital malformationsWell supported
0.83
agreement 0.690.97
Genetic100%Literature0%Genetic literaturedup

Open Targets aggregate 0.72 · 2 independent evidence families · 1 not counted as duplicate

neoplasmModerately supported
0.72
agreement 0.570.88
Clinical95%Literature5%

Open Targets aggregate 0.58 · 2 independent evidence families

small cell lung carcinomaModerately supported
0.69
agreement 0.540.85
Clinical99%Literature1%

Open Targets aggregate 0.56 · 2 independent evidence families

breast cancerModerately supported
0.68
agreement 0.530.84
Clinical96%Literature4%

Open Targets aggregate 0.55 · 2 independent evidence families

small cell carcinomaModerately supported
0.60
agreement 0.430.76
Clinical100%

Open Targets aggregate 0.49 · 1 independent evidence family

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

5

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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.