Protein / target

Trifunctional purine biosynthetic protein adenosine-3

GARTP22102Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
5
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Phosphoribosylformylglycinamidine cyclo-ligase activity

Primary system

Nervous system

Strongest disease association

non-small cell lung carcinoma

Clinical evidence · score 0.61

Therapeutic maturity

Clinically validated target

5 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

5 approved · 1 in clinical development

30 linked trials

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

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.

Metabolic enzyme activityGO
View supporting evidence

Metabolic enzyme activity

  • ·phosphoribosylglycinamide formyltransferase activity
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.

Drugs targeting this protein

1

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.

pemetrexed
Narrow target profileApprovedInhibitor

GAR transformylase inhibitor

Appears in clinical studies involving malignant pleural mesothelioma, mesothelioma, non-small cell lung carcinoma, neoplasm

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

non-small cell lung carcinoma0.99

Clinical · overall 0.61

mesothelioma0.96

Clinical · overall 0.58

malignant pleural mesothelioma0.91

Clinical · overall 0.56

adenocarcinoma0.80

Clinical · overall 0.49

lung large cell carcinoma0.76

Clinical · overall 0.46

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

neoplasm0.41

Literature

non-small cell squamous lung carcinoma0.39

Clinical

lung adenocarcinoma0.39

Clinical

lung cancer0.37

Clinical

cervical cancer0.35

Clinical

Show all associations
non-small cell lung carcinoma0.61
mesothelioma0.58
malignant pleural mesothelioma0.56
adenocarcinoma0.49
lung large cell carcinoma0.46
neoplasm0.41
non-small cell squamous lung carcinoma0.39
lung adenocarcinoma0.39
lung cancer0.37
cervical cancer0.35

Open Targets ranks 281 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 · 6 total

PEMETREXED DISODIUMApproval

non-small cell lung carcinoma · non-small cell lung carcinoma · malignant pleural mesothelioma

PEMETREXED MONOHYDRATEApproval

mesothelioma · non-small cell lung carcinoma

PELITREXOLPhase 2

colorectal cancer · non-small cell lung carcinoma

PEMETREXED TROMETHAMINEApproval

lung large cell carcinoma · adenocarcinoma · mesothelioma

PEMETREXED DIPOTASSIUMApproval

lung large cell carcinoma

PEMETREXEDApproval

malignant pleural mesothelioma · mesothelioma · non-small cell lung carcinoma

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

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.

Show remaining trials (24)

COMPLETED · via pemetrexed · NCT03955042

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

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.

non-small cell lung carcinomaModerately supported
0.75
agreement 0.610.88
Clinical96%Literature3%RNA expression1%

Open Targets aggregate 0.61 · 3 independent evidence families

mesotheliomaModerately supported
0.72
agreement 0.550.88
Clinical100%

Open Targets aggregate 0.58 · 1 independent evidence family

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

lung large cell carcinomaModerately supported
0.57
agreement 0.410.73
Clinical100%

Open Targets aggregate 0.46 · 1 independent evidence family

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

16

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. Withdrawn from market2024-10-09

    Market withdrawal: Pemetrexed Sandoz (EMA)

    ema · market · ema · via pemetrexed

  2. 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

  3. Withdrawn from market2023-10-12

    Market withdrawal: Ciambra (EMA)

    ema · market · ema · via pemetrexed

  4. 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

  5. New publication2020-12-14
    Atezolizumab Plus Chemotherapy for First-Line Treatment of Nonsquamous NSCLC: Results From the Randomized Phase 3 IMpower132 Trial.

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2021 · 352 citations · Europe PMC · via pemetrexed

  6. 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

  7. Regulatory approval2016-07-22

    Approval: Pemetrexed Fresenius Kabi (EMA)

    ema · regulatory · ema · via pemetrexed

  8. Regulatory approval2016-01-18

    Approval: Armisarte (previously Pemetrexed Actavis) (EMA)

    ema · regulatory · ema · via pemetrexed

  9. Regulatory approval2016-01-18

    Approval: Pemetrexed Accord (EMA)

    ema · regulatory · ema · via pemetrexed

  10. Regulatory approval2015-11-26

    Approval: Pemetrexed medac (EMA)

    ema · regulatory · ema · via pemetrexed

  11. Regulatory approval2015-11-19

    Approval: Pemetrexed Pfizer (previously Pemetrexed Hospira) (EMA)

    ema · regulatory · ema · via pemetrexed

  12. 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

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.