Protein / target
Dihydrofolate reductase
Protein at a glance
Biological role
MRNA regulatory element binding translation repressor
Strongest disease association
Inherited cancer-predisposing syndrome
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Catalyzes the reduction of 7,8-dihydrofolate (DHF) to 5,6,7,8-tetrahydrofolate in a NADPH-dependent manner.
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Catalyzes the reduction of 7,8-dihydrofolate (DHF) to 5,6,7,8-tetrahydrofolate in a NADPH-dependent manner (PubMed:12096917, PubMed:15039552, PubMed:17569517, PubMed:19196009, PubMed:19478082, PubMed:21876184, PubMed:9719595). Key enzyme in folate metabolism. Contributes to the nuclear and mitochondrial de novo thymidylate biosynthesis pathway (PubMed:21876188, PubMed:22235121). Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFR2
Subcellular location
Domains and Gene Ontology detail (24)Hide
Domains & features
Gene Ontology
- Ccytosol
- Cmitochondrion
- Cnucleus
- Creplication fork
- Fdihydrofolate reductase activity
- Ffolic acid binding
- FmRNA binding
- FmRNA regulatory element binding translation repressor activity
- FNADP binding
- FNADPH binding
- Fsequence-specific mRNA binding
- 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.
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Metabolic enzyme activity
- ·dihydrofolate metabolic process
- ·folic acid metabolic process
- ·one-carbon metabolic process
- ·tetrahydrofolate metabolic process
View underlying pathways (3)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.
Approved medicines with mapped indications
Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.
Broader indication categories (1)Hide
Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.
8 medicines meet Open Targets' target-level approved-medicine definition; the 2 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
Dihydrofolate reductase inhibitor
Indicated for Mesothelioma, Neoplasms
Dihydrofolate reductase inhibitor
Indicated for Arthritis, Arthritis, Juvenile, Arthritis, Psoriatic, Arthritis, Rheumatoid
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene DHFR
Gene-level evidence surfaced through the gene DHFRthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
View evidence synthesis (5)Hide
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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 per-type scores above show the calculation.
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Drug development
9 compounds recorded · 8 approved · 1 in clinical development
View all recorded compounds (9)Hide
Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Strong
Protein degraders — Emerging
View underlying tractability evidence (8)Hide
Raw Open Targets tractability assessment buckets, by modality.
Safety-related annotations
Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.
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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.
- Trial status changed
Phase I/II Study of Neoadjuvant Inhaled Azacytidine With Platinum-Based Chemotherapy and Durvalumab (MEDI4736) - a Combined Epigenetic-Immunotherapy (AZA-AEGEAN) Regimen for Operable Early-Stage Non-Small Cell Lung Cancer (NSCLC)
- Trial status changed
JS207 (PD-1/VEGF Dual Antibody) Combined With Chemotherapy in First-line Treatment of Advanced Non-small Cell Lung Cancer
- Withdrawn from market
Market withdrawal: Pemetrexed Sandoz (EMA)
- New publicationPhase III KEYNOTE-789 Study of Pemetrexed and Platinum With or Without Pembrolizumab for Tyrosine Kinase Inhibitor‒Resistant, <i>EGFR</i>-Mutant, Metastatic Nonsquamous Non-Small Cell Lung Cancer.
- Withdrawn from market
Market withdrawal: Ciambra (EMA)
- Safety communication
Drug Safety Update: Methotrexate: advise patients to take precautions in the sun to avoid photosensitivity reactions
- New publicationPembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non-Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study.
- Regulatory approval
Approval: Jylamvo (EMA)
- New publicationOsimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer.
- Regulatory approval
Approval: Armisarte (previously Pemetrexed Actavis) (EMA)
- New publicationFirst-line crizotinib versus chemotherapy in ALK-positive lung cancer.
- Regulatory approval
Approval: Alimta (EMA)
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.