Protein / target
Thymidylate synthase
Protein at a glance
Biological role
MRNA regulatory element binding translation repressor activity
Strongest disease association
dyskeratosis congenita, digenic
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
9 approved · 2 in clinical development
Research activity
Emerging research
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
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
Subcellular location
Domains and Gene Ontology detail (19)Hide
Gene Ontology
- Ccytoplasm
- Ccytosol
- Cmitochondrial inner membrane
- Cmitochondrial matrix
- Cmitochondrion
- Cnucleus
- Creplication fork
- Ffolic acid binding
- FmRNA regulatory element binding translation repressor activity
- Fsequence-specific mRNA binding
- Fthymidylate synthase activity
- P'de novo' pyrimidine nucleobase biosynthetic process
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
- ·G1/S-Specific Transcription
View underlying pathways (2)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.
Thymidylate synthase inhibitor
Appears in clinical studies involving adenocarcinoma, keratosis, basal cell carcinoma, head and neck cancer
Thymidylate synthase inhibitor
Appears in clinical studies involving malignant pleural mesothelioma, mesothelioma, non-small cell lung carcinoma, neoplasm
Thymidylate synthase inhibitor
Appears in clinical studies involving breast cancer, breast carcinoma, colonic neoplasm, 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.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
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 647 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
gastric adenocarcinoma · gastroesophageal junction adenocarcinoma · head and neck squamous cell carcinoma
breast cancer · breast carcinoma · colonic neoplasm
non-small cell lung carcinoma · non-small cell lung carcinoma · malignant pleural mesothelioma
rectum adenocarcinoma · neoplasm · colorectal cancer
hepatocellular carcinoma
gastric adenocarcinoma · gastric cancer
gastric cancer · head and neck cancer · non-small cell lung carcinoma
malignant pleural mesothelioma · mesothelioma · non-small cell lung carcinoma
colorectal cancer · neoplasm · malignant colon neoplasm
adenocarcinoma · keratosis · basal cell 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.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.
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.
- Trial results posted
A Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) + Lenvatinib (E7080/MK-7902) + Chemotherapy Compared With Standard of Care as First-line Intervention in Participants With Metastatic Esophageal Carcinoma.
- Trial status changed
A Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) + Lenvatinib (E7080/MK-7902) + Chemotherapy Compared With Standard of Care as First-line Intervention in Participants With Metastatic Esophageal Carcinoma.
- Label change
Label change: CAPECITABINE (ANDA211724)
- Label change
Label change: CAPECITABINE (ANDA210203)
- Label change
Label change: CAPECITABINE (ANDA202593)
- Label change
Label change: CAPECITABINE (ANDA202593)
- Label change
Label change: CAPECITABINE (ANDA202593)
- Label change
Label change: CAPECITABINE (ANDA202593)
- Label change
Label change: CAPECITABINE (ANDA202593)
- Label change
Label change: CAPECITABINE (ANDA202593)
- New publicationEncorafenib, Cetuximab, and mFOLFOX6 in <i>BRAF</i>-Mutated Colorectal Cancer.
- New publicationEncorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.
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.