TOP1 DNA topoisomerase I
ENSG00000198900 · protein coding · Open Targets profile
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. {ECO:0000250|UniProtKB:Q13472, ECO:0000269|PubMed:14594810, ECO:0000269|PubMed:16033260, ECO:0000269|PubMed:19168442, ECO:0000269|PubMed:22904072, ECO:0000269|PubMed:2833744}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 0.09000200033187866 (upper bound 0.15265999734401703). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 400 registry trials, updated in the last three years, of the most advanced drugs against TOP1 (datopotamab deruxtecan, belotecan, irinotecan, topotecan, etirinotecan pegol, patritumab deruxtecan, sacituzumab govitecan, trastuzumab deruxtecan, irinotecan sucrosofate, edotecarin, karenitecin, becatecarin), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Amar GajjarSt. Jude Children's Research Hospital · 2 of 2 trials Phase 2+
- Bristol-Myers SquibbBristol-Myers Squibb · 2 of 2 trials Phase 2+
- Christos FountzilasRoswell Park Cancer Institute · 2 of 2 trials Phase 2+
- Filippo PietrantonioFondazione IRCCS - Istituto Nazionale dei Tumori di Milano · 2 of 2 trials Phase 2+
- Jaume CapdevilaHospital Vall d'hebrón · 2 of 2 trials Phase 2+
- Juan DuThe Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School · 2 of 2 trials Phase 2+
- Jung-min LeeNRG Oncology · 2 of 2 trials Phase 2+
- Sara M. FedericoSt. Jude Children's Research Hospital · 2 of 2 trials Phase 2+
- Funda Meric-BernstamUniversity of Texas MD Anderson Cancer Center LAO · 1 of 2 trials Phase 2+
- Mustafa RaoofCity of Hope Medical Center · 1 of 2 trials Phase 2+
- Susanna UlahannanUniversity of Oklahoma · 1 of 2 trials Phase 2+
- A. Scott PaulsonCharles A. Sammons Cancer Center/Texas Oncology · 1 of 1 trials Phase 2+
- Abha A GuptaChildren's Oncology Group · 1 of 1 trials Phase 2+
- Adam CohenInova Health Care Services · 1 of 1 trials Phase 2+
- Aditi BagchiSt. Jude Children's Research Hospital · 1 of 1 trials Phase 2+
Registry trials of datopotamab deruxtecan, belotecan, irinotecan, topotecan, etirinotecan pegol, patritumab deruxtecan, sacituzumab govitecan, trastuzumab deruxtecan, irinotecan sucrosofate, edotecarin, karenitecin, becatecarin updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 236 of 384 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 16 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
377 trials of drugs against TOP1 were stopped early; 10 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of datopotamab deruxtecan, belotecan, irinotecan, topotecan, etirinotecan pegol, patritumab deruxtecan, sacituzumab govitecan, trastuzumab deruxtecan, irinotecan sucrosofate, edotecarin, karenitecin, becatecarin, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 377.
- terminated · 2026-11-10 · National Cancer Institute (NCI) · Topotecan Hydrochloride“Withdrawal of tazemetostat supply led to early study closure.”
- terminated · 2026-11-04 · Cardiff Oncology · Nanoliposomal irinotecan“Sponsor decision based on meeting essential enrollment and obtaining substantial data to support future pancreatic ductal adenocarcinoma (PDAC) trials in a first-line setting.”
- terminated · 2026-11-03 · Peking University Cancer Hospital & Institute · matched by the registry's drug synonyms“The study was stopped early due to lack of efficacy.”
- terminated · 2026-10-28 · Bristol-Myers Squibb · Topotecan“Business objectives have changed.”
- terminated · 2026-10-21 · University of Nebraska · Irinotecan“Due to low accrual and futility”
- withdrawn · 2026-10-20 · Memorial Sloan Kettering Cancer Center · Trastuzumab Deruxtecan“sponsor closed study”
- terminated · 2026-10-05 · Children's Oncology Group · Irinotecan Hydrochloride“Drug supply issues”
- suspended · 2026-10-02 · University of Alabama at Birmingham · matched by the registry's drug synonyms“temporary suspended”
- terminated · 2026-09-18 · Grupo Espanol de Tumores Neuroendocrinos · matched by the registry's drug synonyms“AMGEN, due to a change in priorities within the Tarlatamab programme, has decided to withdraw its support for the study, which means the clinical trial will be terminated early.”
- terminated · 2026-08-27 · Ludwig-Maximilians - University of Munich · Irinotecan“Funding was withdrawn”
- terminated · 2026-08-26 · Hoffmann-La Roche · irinotecanNo reason given
- suspended · 2026-08-24 · Children's Oncology Group · Irinotecan“Unacceptable Toxicity”
- terminated · 2026-08-14 · Astellas Pharma Global Development, Inc. · Irinotecan“Lack of clinical benefit”
- terminated · 2026-08-03 · Hoffmann-La Roche · Sacituzumab Govitecan“Study was closed early as the sponsor decided not to continue development of certain treatment combinations.”
- terminated · 2026-07-17 · Gilead Sciences · sacituzumab govitecan-hziy“Sponsor decision to terminate”
- terminated · 2026-06-25 · OHSU Knight Cancer Institute · Irinotecan“change in standard-of-care systemic therapy”
- terminated · 2026-06-09 · Regeneron Pharmaceuticals · matched by the registry's drug synonyms“Sponsor Decision related to study drug supply”
- terminated · 2026-06-08 · Weill Medical College of Cornell University · Topotecan“Study terminated due to low accrual”
- suspended · 2026-06-04 · James Cleary, MD, PhD · matched by the registry's drug synonyms“Efficacy concerns.”
- terminated · 2026-05-12 · Hoffmann-La Roche · Sacituzumab Govitecan“Study was closed early as the sponsor decided not to continue development of certain treatment combinations.”
- withdrawn · 2026-05-08 · SynerGene Therapeutics, Inc. · Irinotecan“The grant intended to support this trial as ultimately not funded. This trial was not initiated,. No patients were enrolled.”
- suspended · 2026-05-08 · SynerGene Therapeutics, Inc. · Topotecan“slow recruitment”
- withdrawn · 2026-05-04 · M.D. Anderson Cancer Center · Irinotecan“0 participants”
- withdrawn · 2026-05-01 · MedSIR · Sacituzumab Govitecan (SG)“The interim analysis of the STAR-221 study showed that the domvanalimab combination did not improve overall survival compared to standard of care. No new relevant safety concerns were identified.”
- withdrawn · 2026-04-28 · National Cancer Institute (NCI) · Sacituzumab Govitecan“Study drug supplier withdrew support; no participants were enrolled.”
Paediatric incentives and obligations for TOP1's drugs
For datopotamab deruxtecan, belotecan, irinotecan, topotecan, etirinotecan pegol, patritumab deruxtecan, sacituzumab govitecan, trastuzumab deruxtecan, irinotecan sucrosofate, edotecarin, karenitecin, becatecarin: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · TOP1 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMA/PE/0000228097 (sacituzumab govitecan, Treatment of endometrial carcinoma): W: decision granting a waiver in all age groups for all conditions or indications, 28 Jan 2025; EMEA-002978-PIP02-24 (trastuzumab deruxtecan, Treatment of all conditions in the category of malignant neoplasms (except haematopoietic and lymphoid tissue neoplasms)): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 5 Dec 2024; EMEA-003416-PIP01-23 (irinotecan, Treatment of pancreatic cancer): W: decision granting a waiver in all age groups for all conditions or indications, 14 Jun 2023; EMEA-002645-PIP03-21 (sacituzumab govitecan, Treatment of lung carcinoma (small cell and non-small cell carcinoma)): W: decision granting a waiver in all age groups for all conditions or indications, 13 May 2022; +6 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/14/1343 withdrawn 15 Oct 2014: Treatment of pancreatic cancer; EU/3/06/388 withdrawn 25 Jul 2006: Treatment of cancers of the biliary tree; EU/3/07/504 withdrawn 30 Nov 2007: Treatment of glioma; EU/3/08/562 positive 5 Sept 2008: Treatment of gliomaRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Enhertu: authorised since 18 Jan 2021, conditional; Datroway: authorised since 4 Apr 2025; Trodelvy: authorised since 22 Nov 2021; Topotecan Hospira: authorised since 9 Jun 2010; +9 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of datopotamab deruxtecan, belotecan, irinotecan, topotecan, etirinotecan pegol, patritumab deruxtecan, sacituzumab govitecan, trastuzumab deruxtecan, irinotecan sucrosofate, edotecarin, karenitecin, becatecarinRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 346 interventional studies of datopotamab deruxtecan, belotecan, irinotecan, topotecan, etirinotecan pegol, patritumab deruxtecan, sacituzumab govitecan, trastuzumab deruxtecan, irinotecan sucrosofate, edotecarin, karenitecin, becatecarin include patients under 18; 98 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 26 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.