Protein / target
DNA topoisomerase 1
Protein at a glance
Biological role
Protein serine/threonine kinase activity
Strongest disease association
small cell lung carcinoma
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
10 approved · 16 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
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the BMAL1 promoter
Subcellular location
Domains and Gene Ontology detail (39)Hide
Domains & features
Gene Ontology
- Cchromosome
- Cdense fibrillar component
- Cfibrillar center
- Cnucleolus
- Cnucleoplasm
- Cnucleus
- CP-body
- Cperikaryon
- Cprotein-DNA complex
- FATP binding
- Fchromatin binding
- Fchromatin DNA 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
- ·Releases the supercoiling and torsional tension of DNA introduced during the DNA replica…
- ·RNA polymerase II cis-regulatory region sequence-specific DNA binding
- ·circadian regulation of gene expression
- ·rRNA transcription
Kinase signalling
- ·protein serine/threonine kinase activity
Apoptosis & cell death
- ·programmed cell death
View underlying pathways (1)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 I inhibitor
Appears in clinical studies involving breast cancer, HER2 positive breast carcinoma, breast neoplasm, neoplasm
DNA topoisomerase I inhibitor
Appears in clinical studies involving breast cancer, urothelial carcinoma, triple-negative breast carcinoma, breast neoplasm
DNA topoisomerase I inhibitor
Appears in clinical studies involving neoplasm, non-small cell lung carcinoma, breast cancer, colorectal cancer
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 539 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 · 26 total
small cell lung carcinoma
ovarian cancer · small cell lung carcinoma · cervical cancer
colorectal cancer
small cell lung carcinoma
breast cancer · breast neoplasm · neoplasm
glioblastoma · myelodysplastic syndrome · chronic myelomonocytic leukemia
neoplasm · small cell lung carcinoma · cervical carcinoma
carcinoma · adenocarcinoma · pancreatic neoplasm
breast cancer · urothelial carcinoma · triple-negative breast carcinoma
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 3 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Indication expanded
Indication expansion: SACITUZUMAB GOVITECAN (BLA761115)
- Indication expanded
Indication expansion: SACITUZUMAB GOVITECAN (BLA761115)
- New publicationSacituzumab Govitecan plus Pembrolizumab for Advanced Triple-Negative Breast Cancer.
- New publicationPatritumab deruxtecan in leptomeningeal metastatic disease of solid tumors: the phase 2 TUXEDO-3 trial.
- New publicationEffective extracellular payload release and immunomodulatory interactions govern the therapeutic effect of trastuzumab deruxtecan (T-DXd).
- Label change
Label change: SACITUZUMAB GOVITECAN (BLA761115)
- New publicationTrastuzumab Deruxtecan with Nivolumab in HER2-Expressing Metastatic Breast or Urothelial Cancer: Analysis of the Phase Ib DS8201-A-U105 Study.
- Indication expanded
Indication expansion: SACITUZUMAB GOVITECAN (BLA761115)
- New publicationSacituzumab govitecan in HR<sup>+</sup>HER2<sup>-</sup> metastatic breast cancer: the randomized phase 3 EVER-132-002 trial.
- New publicationReal-World Clinical Outcomes With Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.
- New publicationTrastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial.
- New publicationFDA approval summary: fam-trastuzumab deruxtecan-nxki for unresectable or metastatic non-small cell lung cancer with activating HER2 mutations.
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.