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Protein / target

Glutamate carboxypeptidase 2

Encoded byFOLH1Q04609Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Tetrahydrofolyl-poly(glutamate) polymer binding

Strongest disease association

Venous Thromboembolism

Via encoding gene FOLH1 · Genetic evidence · score 0.60

Therapeutic position

Established drug target

Small molecules and antibodies

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

Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity.

View complete UniProt function annotation

Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate. In the brain, modulates excitatory neurotransmission through the hydrolysis of the neuropeptide, N-aceylaspartylglutamate (NAAG), thereby releasing glutamate. Involved in prostate tumor progression

Subcellular location

Cell membraneCytoplasm
Domains and Gene Ontology detail (16)

Gene Ontology

  • Ccell surface
  • Ccytoplasm
  • Cextracellular exosome
  • Cmembrane
  • Cplasma membrane
  • FAc-Asp-Glu binding
  • Fcarboxypeptidase activity
  • Fdipeptidase activity
  • Fmetal ion binding
  • Fmetallocarboxypeptidase activity
  • Fpeptidase activity
  • Ftetrahydrofolyl-poly(glutamate) polymer binding

750 aa · 84 kDa · 8 isoforms

Biological roles

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

ProteolysisGO
View supporting evidence

Proteolysis

  • ·carboxypeptidase activity
  • ·dipeptidase activity
  • ·metallocarboxypeptidase activity
  • ·peptidase activity

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

Approved medicines with mapped indications

1 medicine · 1 area

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.

Prostatic Neoplasms, Castration-Resistant1 medicine

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.

lutetium Lu 177 vipivotide tetraxetan
Narrow target profileBinding agent

Glutamate carboxypeptidase II binding agent

Indicated for Prostatic Neoplasms, Castration-Resistant

Direct interaction with this protein · Only this protein recorded as a target

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 FOLH1

Gene-level evidence surfaced through the gene FOLH1 that 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.

Prostatic Neoplasms
0.72Moderately supported

Clinical evidence dominant · Open Targets 0.57

Venous Thromboembolism
0.60Moderately supported

Genetic evidence dominant · Open Targets 0.36

Retinal Diseases
0.60Moderately supported

Genetic evidence dominant · Open Targets 0.36

Diabetes Mellitus, Type 2
0.59Moderately supported

Genetic evidence dominant · Open Targets 0.36

Pulmonary Embolism
0.49Limited support

Genetic evidence dominant · Open Targets 0.30

View evidence synthesis (5)
Prostatic NeoplasmsModerately supported
0.72
agreement 0.560.87
Clinical82%Literature18%

Open Targets aggregate 0.57 · 2 independent evidence families

Venous ThromboembolismModerately supported
0.60
agreement 0.460.74
Genetic100%Literature0%

Open Targets aggregate 0.36 · 2 independent evidence families

Retinal DiseasesModerately supported
0.60
agreement 0.460.74
Genetic96%Literature4%

Open Targets aggregate 0.36 · 2 independent evidence families

Diabetes Mellitus, Type 2Moderately supported
0.59
agreement 0.450.73
Genetic98%Literature2%

Open Targets aggregate 0.36 · 2 independent evidence families

Pulmonary EmbolismLimited support
0.49
agreement 0.370.61
Genetic100%

Open Targets aggregate 0.30 · 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 per-type scores above show the calculation.

Show all associations
Prostatic Neoplasms0.57
Venous Thromboembolism0.36
Retinal Diseases0.36
Diabetes Mellitus, Type 20.36
Carcinoma, Renal Cell0.30
Pulmonary Embolism0.30
Pulmonary Heart Disease0.30
Neuroendocrine Tumors0.29

Drug development

6 compounds recorded · 1 approved · 5 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)
HUJ591 111INPhase 2
MLN-2704Phase 1 2
HUJ591 177LUPhase 2
MDX-070Phase 2
LUTETIUM LU-177 VIPIVOTIDE TETRAXETANApproval
CYT-500 177LUPhase 1

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.

AntibodiesStrong

Advanced Clinical and UniProt loc high conf support this modality.

Protein degradersEmerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (11)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · Advanced ClinicalAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

hematological toxicityClinPGx

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

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)

ACTIVE_NOT_RECRUITING · via lutetium Lu 177 vipivotide tetraxetan · NCT06964958

RECRUITING · via lutetium Lu 177 vipivotide tetraxetan · NCT06526299

RECRUITING · via lutetium Lu 177 vipivotide tetraxetan · NCT06632977

ACTIVE_NOT_RECRUITING · via lutetium Lu 177 vipivotide tetraxetan · NCT05340374

ACTIVE_NOT_RECRUITING · via lutetium Lu 177 vipivotide tetraxetan · NCT03042468

ClinicalTrials.gov via the drug-target graph.

What's happening now

6

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. Indication expanded2026-07-31

    Indication expansion: LUTETIUM LU 177 VIPIVOTIDE TETRAXETAN (NDA215833)

    fda · regulatory · fda · via lutetium Lu 177 vipivotide tetraxetan

  2. Label change2026-04-07

    Label change: LUTETIUM LU 177 VIPIVOTIDE TETRAXETAN (NDA215833)

    fda · regulatory · fda · via lutetium Lu 177 vipivotide tetraxetan

  3. Indication expanded2025-03-28

    Indication expansion: LUTETIUM LU 177 VIPIVOTIDE TETRAXETAN (NDA215833)

    fda · regulatory · fda · via lutetium Lu 177 vipivotide tetraxetan

  4. Label change2025-03-28

    Label change: LUTETIUM LU 177 VIPIVOTIDE TETRAXETAN (NDA215833)

    fda · regulatory · fda · via lutetium Lu 177 vipivotide tetraxetan

  5. Regulatory approval2022-03-23

    Approval: LUTETIUM LU 177 VIPIVOTIDE TETRAXETAN (NDA215833)

    fda · regulatory · fda · via lutetium Lu 177 vipivotide tetraxetan

  6. New publication2021-06-23
    Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer.

    The New England journal of medicine · 2021 · 1,942 citations · Europe PMC · via lutetium Lu 177 vipivotide tetraxetan

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.