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Protein / target

Trifunctional purine biosynthetic protein adenosine-3

Encoded byGARTP22102Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
5
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Phosphoribosylformylglycinamidine cyclo-ligase

Strongest disease association

Carcinoma, Non-Small-Cell Lung

Via encoding gene GART · Clinical evidence · score 0.61

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway

Domains and Gene Ontology detail (18)

Domains & features

ATP-grasp

Gene Ontology

  • Ccytosol
  • Cextracellular exosome
  • FATP binding
  • Fmetal ion binding
  • Fphosphoribosylamine-glycine ligase activity
  • Fphosphoribosylformylglycinamidine cyclo-ligase activity
  • Fphosphoribosylglycinamide formyltransferase activity
  • P'de novo' AMP biosynthetic process
  • P'de novo' IMP biosynthetic process
  • P'de novo' XMP biosynthetic process
  • Padenine biosynthetic process
  • Pbrainstem development

1010 aa · 108 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

View underlying pathways (1)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

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.

MTHFD2PPATATICSHMT2MTHFD1LADSLMTHFD1PFASMTHFD2LPAICSGART

10 strongest partners — larger node and heavier line mean higher confidence

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

1 medicine · 2 areas

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.

Mesothelioma1 medicine
Broader indication categories (1)
Neoplasms1 medicine

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.

5 medicines meet Open Targets' target-level approved-medicine definition; the 1 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

1

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.

pemetrexed
Narrow target profileApprovedInhibitor

GAR transformylase inhibitor

Indicated for Mesothelioma, Neoplasms

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

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 GART

Gene-level evidence surfaced through the gene GARTthat 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.

Carcinoma, Non-Small-Cell Lung
0.75Moderately supported

Clinical evidence dominant · Open Targets 0.61

Malignant pleural mesothelioma
0.69Moderately supported

Clinical evidence dominant · Open Targets 0.56

Adenocarcinoma
0.60Moderately supported

Clinical evidence dominant · Open Targets 0.49

Neoplasms
0.54Moderately supported

Clinical evidence dominant · Open Targets 0.41

Adenocarcinoma of Lung
0.49Limited support

Clinical evidence dominant · Open Targets 0.39

View evidence synthesis (5)
Carcinoma, Non-Small-Cell LungModerately supported
0.75
agreement 0.610.88
Clinical96%Literature3%RNA expression1%

Open Targets aggregate 0.61 · 3 independent evidence families

Malignant pleural mesotheliomaModerately supported
0.69
agreement 0.530.84
Clinical100%Literature0%

Open Targets aggregate 0.56 · 2 independent evidence families

AdenocarcinomaModerately supported
0.60
agreement 0.450.76
Clinical100%Literature1%

Open Targets aggregate 0.49 · 2 independent evidence families

NeoplasmsModerately supported
0.54
agreement 0.380.69
Clinical82%Literature18%

Open Targets aggregate 0.41 · 2 independent evidence families

Adenocarcinoma of LungLimited support
0.49
agreement 0.350.63
Clinical94%RNA expression4%Literature2%

Open Targets aggregate 0.39 · 3 independent evidence families

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.

Show all associations
Carcinoma, Non-Small-Cell Lung0.61
Malignant pleural mesothelioma0.56
Adenocarcinoma0.49
Neoplasms0.41
Adenocarcinoma of Lung0.39
Lung Neoplasms0.37
Uterine Cervical Neoplasms0.35

Drug development

6 compounds recorded · 5 approved · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (6)
PEMETREXED DISODIUMApproval
PEMETREXED MONOHYDRATEApproval
PELITREXOLPhase 2
PEMETREXED TROMETHAMINEApproval
PEMETREXED DIPOTASSIUMApproval
PEMETREXEDApproval

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 moleculesStrong

Approved Drug and Structure with Ligand support this modality.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

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)

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets 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.

  1. Trial status changed2026-08-25

    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)

    Status changed to Suspended · ClinicalTrials.gov · via pemetrexed

  2. Trial status changed2026-08-04

    JS207 (PD-1/VEGF Dual Antibody) Combined With Chemotherapy in First-line Treatment of Advanced Non-small Cell Lung Cancer

    Status changed to Active, not recruiting · ClinicalTrials.gov · via pemetrexed

  3. Withdrawn from market2024-10-09

    Market withdrawal: Pemetrexed Sandoz (EMA)

    ema · market · ema · via pemetrexed

  4. New publication2024-08-22
    Phase 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.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024 · 162 citations · Europe PMC · via pemetrexed

  5. Withdrawn from market2023-10-12

    Market withdrawal: Ciambra (EMA)

    ema · market · ema · via pemetrexed

  6. New publication2023-02-21
    Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non-Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023 · 505 citations · Europe PMC · via pemetrexed

  7. New publication2016-12-06
    Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer.

    The New England journal of medicine · 2017 · 2,677 citations · Europe PMC · via pemetrexed

  8. Regulatory approval2016-07-22

    Approval: Pemetrexed Fresenius Kabi (EMA)

    ema · regulatory · ema · via pemetrexed

  9. Regulatory approval2016-01-18

    Approval: Armisarte (previously Pemetrexed Actavis) (EMA)

    ema · regulatory · ema · via pemetrexed

  10. Regulatory approval2016-01-18

    Approval: Pemetrexed Accord (EMA)

    ema · regulatory · ema · via pemetrexed

  11. New publication2014-12-01
    First-line crizotinib versus chemotherapy in ALK-positive lung cancer.

    The New England journal of medicine · 2014 · 2,470 citations · Europe PMC · via pemetrexed

  12. Regulatory approval2004-09-20

    Approval: Alimta (EMA)

    ema · regulatory · ema · via pemetrexed

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.