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Protein / target

Neprilysin

Encoded byMMEP08473Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
2
Approved medicines
Open Targets target-level
Small-molecule tractable
Druggability
Approved Drug
1
Research papers

Protein at a glance

Biological role

Protein homodimerization

Strongest disease association

Genetic Diseases, Inborn

Via encoding gene MME · Genetic evidence · score 0.68

Therapeutic position

Established drug target

Small molecules

Research activity

Emerging research

1 papers · latest 2014

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

Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids.

View complete UniProt function annotation

Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:6208535, PubMed:6349683, PubMed:8168535). Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (PubMed:17101991, PubMed:6349683). Catalyzes cleavage of bradykinin, substance P and neurotensin peptides (PubMed:6208535). Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (PubMed:15283675, PubMed:6349683). Involved in the degradation of atrial natriuretic factor (ANF) and brain natriuretic factor (BNP(1-32)) (PubMed:16254193, PubMed:2531377, PubMed:2972276). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers (PubMed:20876573)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (55)

Domains & features

Peptidase M13

Gene Ontology

  • Caxon
  • Cbrush border
  • Ccell surface
  • Ccytoplasm
  • Ccytoplasmic vesicle
  • Cdendrite
  • Cearly endosome
  • Cextracellular exosome
  • Cfocal adhesion
  • Cmembrane
  • Cmembrane raft
  • Cneuron projection terminus

750 aa · 86 kDa

Biological roles

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

ProteolysisGOMetabolic enzyme activityGO
View supporting evidence

Proteolysis

  • ·endopeptidase activity
  • ·exopeptidase activity
  • ·metallocarboxypeptidase activity
  • ·metalloendopeptidase activity

Metabolic enzyme activity

  • ·amyloid-beta metabolic process
  • ·creatinine metabolic process
  • ·peptide metabolic process

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

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 MME

Gene-level evidence surfaced through the gene MME 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.

Heart Failure
0.76Well supported

Clinical evidence dominant · Open Targets 0.61

Genetic Diseases, Inborn
0.69Moderately supported

Genetic evidence dominant · Open Targets 0.42

View evidence synthesis (2)
Heart FailureWell supported
0.76
agreement 0.600.91
Clinical87%Literature13%

Open Targets aggregate 0.61 · 2 independent evidence families

Genetic Diseases, InbornModerately supported
0.69
agreement 0.550.82
Genetic99%Literature1%

Open Targets aggregate 0.42 · 2 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
Heart Failure0.61
Genetic Diseases, Inborn0.42

Drug development

4 compounds recorded · 2 approved · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (4)
RACECADOTRILApproval
DAGLUTRILPhase 2
SACUBITRILApproval
ILEPATRILPhase 2 3

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.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

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

View underlying tractability evidence (10)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

coughClinPGx

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.

Research activity

1 papers · to 2014

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

McMurray JJ · The New England journal of medicine · 2014

Recent

Angiotensin-neprilysin inhibition versus enalapril in heart failure.

McMurray JJ · The New England journal of medicine · 2014

Europe PMC papers linked directly to this protein.