TYMS thymidylate synthetase
ENSG00000176890 · protein coding · Open Targets profile
Catalyzes the reductive methylation of 2'-deoxyuridine 5'- monophosphate (dUMP) to thymidine 5'-monophosphate (dTMP), using the cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1- carbon donor and reductant and contributes to the mitochondrial and nuclear de novo thymidylate biosynthesis pathway. {ECO:0000269|PubMed:11278511, ECO:0000269|PubMed:21876188, ECO:0000269|PubMed:22235121}.
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 Withdrawn means the drug was pulled from the market or from development.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, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.5350099802017212 (upper bound 0.7704200148582458). 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 TYMS (pemetrexed, raltitrexed, doxifluridine, tegafur, floxuridine, fluorouracil, nolatrexed, OSI-7904), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Jinbo YueShandong Cancer Hospital and Institute · 3 of 3 trials Phase 2+Ph3NCT06850090 · Neoadjuvant Radiotherapy for Rectal Adenocarcinoma With Capecitabine Versus TAS-102 (Neo-REACT): A Multi-center, Randomized, Phase III Trialbrief
- Andrea CercekMemorial Sloan Kettering Cancer Center · 2 of 2 trials Phase 2+
- Bristol-Myers SquibbBristol-Myers Squibb · 2 of 2 trials Phase 2+
- ruihua xuSun Yat-Sen University Cancer Center · 2 of 2 trials Phase 2+
- Zhenyu PanJinshan Hospital Fudan University · 2 of 2 trials Phase 2+
- Abdullah EsmailHouston Methodist Nael Cancer Center · 1 of 3 trials Phase 2+
- Anne S TsaoSWOG Cancer Research Network · 1 of 2 trials Phase 2+
- Jeffrey WongCity of Hope Medical Center · 1 of 2 trials Phase 2+
- A P ChenNational Cancer Institute LAO · 1 of 1 trials Phase 2+
- A. Scott PaulsonCharles A. Sammons Cancer Center/Texas Oncology · 1 of 1 trials Phase 2+
- Aaron S MansfieldAlliance for Clinical Trials in Oncology · 1 of 1 trials Phase 2+
- Adam J EsbenshadeChildren's Oncology Group · 1 of 1 trials Phase 2+
- Aiping ZhouCancer Institute and Hospital, Chinese Academy of Medical Sciences · 1 of 1 trials Phase 2+
- Aminah JatoiMayo Clinic · 1 of 1 trials Phase 2+
- Anna NowakFaculty of Health and Medical Sciences University of Western Australia · 1 of 1 trials Phase 2+
Registry trials of pemetrexed, raltitrexed, doxifluridine, tegafur, floxuridine, fluorouracil, nolatrexed, OSI-7904 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; 217 of 378 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. 22 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
918 trials of drugs against TYMS were stopped early; 4 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of pemetrexed, raltitrexed, doxifluridine, tegafur, floxuridine, fluorouracil, nolatrexed, OSI-7904, 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 918.
- suspended · 2026-11-10 · National Cancer Institute (NCI) · pemetrexed“Placed on voluntary hold to new recruitment pending modification to combination monoclonal antibody treatment.”
- terminated · 2026-11-04 · Cardiff Oncology · Fluorouracil“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 · 2026-11-04 · InnoPharmax Inc. · matched by the registry's drug synonyms“Dose-finding stage has been completed, and dose-expanding stage was not conducted due to design amendment.”
- 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 · 2026-10-30 · Tufts Medical Center · pemetrexed“Futility”
- terminated · 2026-10-22 · Oslo University Hospital · Floxuridine“Following temporary halt of inclusion in September 2024, several measures were taken, as previuosly reported. As numbers included by September 2024 were sufficient to conclude for primary endpont, we have decided not to restart the trial.”
- terminated · 2026-10-21 · University of Nebraska · 5Fluorouracil“Due to low accrual and futility”
- terminated · 2026-10-15 · Spanish Breast Cancer Research Group · matched by the registry's drug synonyms“Study prematurely terminated due to recruitment challenges, low incidence of the target population, evolving treatment landscape, ethical considerations, and inability to ensure funding through study completion.”
- terminated · 2026-10-08 · Jin Hyoung Kang · Pemetrexed“Slow accrual; enrollment was closed after 14 of 28 planned participants.”
- terminated · 2026-10-06 · Processa Pharmaceuticals · matched by the registry's drug synonyms“Business Reason”
- terminated · 2026-10-02 · Ralf Hofheinz · matched by the registry's drug synonyms“poor accrual”
- suspended · 2026-10-02 · University of Alabama at Birmingham · matched by the registry's drug synonyms“temporary suspended”
- terminated · 2026-09-30 · Breast Cancer Trials, Australia and New Zealand · matched by the registry's drug synonyms“Stopped on the recommendation of the BCT Independent Data and Monitoring Committee”
- terminated · 2026-09-30 · Alaunos Therapeutics · matched by the registry's drug synonyms“No dose-limiting toxicity was observed. The sponsor concluded the study after 3 subjects at the higher dose level; the optional 10-subject expansion cohort was not enrolled.”
- terminated · 2026-09-29 · Sanofi · Pemetrexed“Early discontinuation based on strategic sponsor decision not driven by any safety concerns”
- withdrawn · 2026-09-23 · Fifth Affiliated Hospital, Sun Yat-Sen University · matched by the registry's drug synonyms“The study was terminated because the protocol was upgraded after being considered insufficiently advanced.”
- terminated · 2026-09-23 · Hackensack Meridian Health · Pemetrexed“Slow Accrual”
- 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 · 2026-09-17 · Centre Oscar Lambret · matched by the registry's drug synonyms“Analysis conducted on spring 2025, according to the provisional schedule: the results were sufficient to conclude about all endpoints, and the sponsor defined a new end of trial on 27 Dec 2025 (modification approved on CTIS on May 26, 2026).”
- terminated · 2026-09-11 · Merck Sharp & Dohme LLC · Pemetrexed“MK-7684A-007 was terminated early due to futility. A non-submission CSR, not intended to support any registration, was issued; therefore, an abbreviated CSR was generated.”
- terminated · 2026-09-10 · Amgen · matched by the registry's drug synonyms“Study was terminated by sponsor”
- terminated · 2026-09-08 · ETOP IBCSG Partners Foundation · matched by the registry's drug synonyms“Completion of recruitment was not feasible as accrual was slower than anticipated. Even if a benefit for denosumab could be shown, these results would be of very limited clinical impact by the time they would be available”
- terminated · 2026-09-03 · GlaxoSmithKline · Pemetrexed+ (carboplatin or cisplatin)“Operational challenges”
- terminated · 2026-08-27 · Ludwig-Maximilians - University of Munich · matched by the registry's drug synonyms“Funding was withdrawn”
- terminated · 2026-08-26 · Hoffmann-La Roche · matched by the registry's drug synonymsNo reason given
Paediatric incentives and obligations for TYMS's drugs
For pemetrexed, raltitrexed, doxifluridine, tegafur, floxuridine, fluorouracil, nolatrexed, OSI-7904: 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: yes · TYMS is on the list. Membership alone neither requires nor waives a pediatric study.Rule: 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 · EMEA-000650-PIP01-09 (Fluorouracil;salicylic acid, Treatment of actinic keratosis): W: decision granting a waiver in all age groups for all conditions or indications, 1 Dec 2009; EMEA-000400-PIP01-08 (raltitrexed, Mesothelioma of the pleura): W: decision granting a waiver in all age groups for all conditions or indications, 27 Jan 2009Rule: 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/3/07/515 withdrawn 20 Dec 2007: Treatment of gastric cancer; EU/3/00/004 withdrawn 18 Oct 2000: Treatment of glioblastoma; EU/3/03/165 withdrawn 2 Oct 2003: Treatment of hepatocellular carcinomaRule: 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 · Pemetrexed medac: withdrawn since 26 Nov 2015; Pemetrexed Baxter: withdrawn since 9 Dec 2022; Alimta: authorised since 20 Sept 2004; Pemetrexed Accord: authorised since 18 Jan 2016; +10 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 pemetrexed, raltitrexed, doxifluridine, tegafur, floxuridine, fluorouracil, nolatrexed, osi-7904Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 276 interventional studies of pemetrexed, raltitrexed, doxifluridine, tegafur, floxuridine, fluorouracil, nolatrexed, osi-7904 include patients under 18; 35 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, 2026-11-11
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 10 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.