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Protein / target

Complement C5

Encoded byC5P01031Homo sapiensSwiss-Prot
UniProt: P01031Ensembl: ENSG00000106804HGNC: HGNC:1331NCBI Gene: 727
Clinically validated
Therapeutic maturity
8
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

Endopeptidase inhibitor

Strongest disease association

Myasthenia Gravis

Via encoding gene C5 · Clinical evidence · score 0.59

Therapeutic position

Established drug target

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

Precursor of the C5a anaphylatoxin and complement C5b components of the complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system.

View complete UniProt function annotation

Precursor of the C5a anaphylatoxin and complement C5b components of the complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:12878586, PubMed:18204047, PubMed:30643019, PubMed:6554279). Activated downstream of classical, alternative, lectin and GZMK complement pathways (PubMed:12878586, PubMed:18204047, PubMed:30643019, PubMed:39914456, PubMed:39814882, PubMed:6554279)

Subcellular location

SecretedTarget cell membrane
Domains and Gene Ontology detail (21)

Domains & features

Anaphylatoxin-likeNTR

Gene Ontology

  • Cextracellular exosome
  • Cextracellular region
  • Cextracellular space
  • Cmembrane attack complex
  • Cother organism cell membrane
  • Fchemokine activity
  • Fendopeptidase inhibitor activity
  • Fsignaling receptor binding
  • Pcell surface receptor signaling pathway
  • Pchemotaxis
  • Pcomplement activation, alternative pathway
  • Pcomplement activation, classical pathway

1676 aa · 188 kDa

Biological roles

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

Cell migrationGO
View supporting evidence

Cell migration

  • ·chemotaxis
  • ·negative regulation of macrophage chemotaxis

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

Approved medicines with mapped indications

3 medicines · 4 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.

Hemoglobinuria, Paroxysmal3 medicines
crovalimabeculizumabravulizumab
Hemoglobinuria2 medicines
eculizumabravulizumab
Atypical Hemolytic Uremic Syndrome1 medicine
eculizumab
Hemolytic-Uremic Syndrome1 medicine
ravulizumab

8 medicines meet Open Targets' target-level approved-medicine definition; the 3 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

5

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.

eculizumab
Narrow target profileApprovedInhibitor

Complement C5 inhibitor

Indicated for Atypical Hemolytic Uremic Syndrome, Hemoglobinuria, Hemoglobinuria, Paroxysmal

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

crovalimab
Narrow target profileApprovedInhibitor

Complement C5 inhibitor

Indicated for Hemoglobinuria, Paroxysmal

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

ravulizumab
Narrow target profileApprovedInhibitor

Complement C5 inhibitor

Indicated for Hemoglobinuria, Hemoglobinuria, Paroxysmal, Hemolytic-Uremic Syndrome

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

vilobelimab
Narrow target profileApprovedInhibitor

Complement C5 inhibitor

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

zilucoplan
Narrow target profileApprovedInhibitor

Complement C5 inhibitor

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 C5

Gene-level evidence surfaced through the gene C5 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.

Myasthenia Gravis
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.59

Neuromyelitis Optica
0.64Moderately supported

Clinical evidence dominant · Open Targets 0.52

Macular Degeneration
0.63Moderately supported

Clinical evidence dominant · Open Targets 0.49

View evidence synthesis (3)
Myasthenia GravisModerately supported
0.73
agreement 0.57–0.89
Clinical86%Literature14%

Open Targets aggregate 0.59 · 2 independent evidence families

Neuromyelitis OpticaModerately supported
0.64
agreement 0.49–0.80
Clinical94%Literature6%

Open Targets aggregate 0.52 · 2 independent evidence families

Macular DegenerationModerately supported
0.63
agreement 0.47–0.78
Clinical87%Literature14%

Open Targets aggregate 0.49 · 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
Myasthenia Gravis0.59
Neuromyelitis Optica0.52
Macular Degeneration0.49

Drug development

13 compounds recorded · 8 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 5 drugs that target this protein in Forefront's canonical graph (3 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
POZELIMABApproval
OLENDALIZUMABPhase 2
PEXELIZUMABPhase 3
VILOBELIMABApproval
ECULIZUMABApproval
ZILUCOPLANApproval
NOMACOPANPhase 3
TESIDOLUMABPhase 2
RAVULIZUMABApproval
AVACINCAPTAD PEGOL SODIUMApproval

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 — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Strong

Approved Drug and UniProt loc high conf support this modality.

Protein degraders — Emerging

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

Other modalities — Strong

Approved Drug support this modality.

View underlying tractability evidence (11)
SM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketAB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule BinderOC · Approved Drug

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.

A Comparative Clinical Effectiveness Trial of Rituximab Versus Ravulizumab, Inebilizumab, Satralizumab and Eculizumab To Prevent Relapses in Neuromyelitis Optica Spectrum DisorderPHASE4

NOT_YET_RECRUITING · via eculizumab · NCT07010302

OCTAGON: A Phase 4, Single Arm Study to Investigate Oral Corticosteroid Tapering in Adult Patients With Generalized Myasthenia Gravis Treated With RavulizumabPHASE4

RECRUITING · via ravulizumab · NCT07221838

An Open-Label Extension Study to Evaluate the Long-Term Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Activity of Zilucoplan in Pediatric Study Participants With Acetylcholine Receptor Antibody Positive Generalized Myasthenia GravisPHASE3

ENROLLING_BY_INVITATION · via zilucoplan · NCT06435312

A Phase III, Multicenter, Single-Arm Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Pediatric Patients With Atypical Hemolytic Uremic Syndrome (aHUS)PHASE3

ACTIVE_NOT_RECRUITING · via crovalimab · NCT04958265

View all trials (26)
Multicenter, Open-label, Single-arm, Post-Marketing Clinical Study to Evaluate the Efficacy and Safety of Ravulizumab in Participants Clinically Diagnosed as Atypical Hemolytic Uremic SyndromePHASE4

RECRUITING · via ravulizumab · NCT07308574

A Phase 3b, Open-label, Single-arm, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Ravulizumab in Chinese Adult Participants With Neuromyelitis Optica Spectrum Disorder (NMOSD)PHASE3

NOT_YET_RECRUITING · via ravulizumab · NCT07557420

An Open-label, Single-arm, Multi-center, Interventional Study to Evaluate the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Ravulizumab in Chinese Adult Patients With Generalized Myasthenia Gravis (gMG)PHASE3

NOT_YET_RECRUITING · via ravulizumab · NCT07596784

A Multicenter, Randomized, Open-label, Active-controlled Phase III Clinical Trial Evaluating the Efficacy and Safety of NTQ5082 Capsules in the Treatment of Patients With Paroxysmal Nocturnal HemoglobinuriaPHASE3

NOT_YET_RECRUITING · via eculizumab · NCT07177859

A Phase 3, Open-Label, Multicenter Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of Ravulizumab in Pediatric Participants (2 to < 18 Years of Age) With Primary Immunoglobulin A Nephropathy (IgAN)PHASE3

RECRUITING · via ravulizumab · NCT07024563

A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Ravulizumab Administered Intravenously in Adult Participants at High Risk of Delayed Graft Function After Kidney TransplantationPHASE3

RECRUITING · via ravulizumab · NCT06830798

An Open-label, Single-arm, Multi-Center, Interventional Study to Evaluate the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Eculizumab in Chinese Adult Participants With Anti-Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorders (NMOSD)PHASE3

ACTIVE_NOT_RECRUITING · via eculizumab · NCT06724809

A Multicenter Open-Label, Uncontrolled Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Activity of Zilucoplan in Pediatric Study Participants From 2 to Less Than 18 Years of Age With Acetylcholine Receptor Antibody Positive Generalized Myasthenia GravisPHASE2/PHASE3

RECRUITING · via zilucoplan · NCT06055959

A Randomized, Multicenter, Active-comparator Controlled, Open-label Trial to Evaluate Efficacy and Safety of MY008211A Tablets in PNH Patients Who Are Naive to Complement Inhibitor TherapyPHASE3

RECRUITING · via eculizumab · NCT06932744

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Participants With Immunoglobulin A Nephropathy (IgAN)PHASE3

ACTIVE_NOT_RECRUITING · via ravulizumab · NCT06291376

Phase 3, Open-label, Single-arm, Multicenter Study Evaluating Pharmacokinetics, Pharmacodynamics, Efficacy, Safety, and Immunogenicity of IV Ravulizumab in Pediatric Participants (6 to <18 Years) With Generalized Myasthenia Gravis (gMG)PHASE3

ACTIVE_NOT_RECRUITING · via ravulizumab · NCT05644561

A Randomized, Open-Label, C5 Inhibitor-Controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Are Complement Inhibitor Treatment-Naive or Have Not Recently Received Complement Inhibitor TherapyPHASE3

ACTIVE_NOT_RECRUITING · via ravulizumab · NCT05133531

A Phase 2/3, Open-label, Historical-controlled, Single-arm, Multicenter Study to Evaluate the Efficacy, Pharmacokinetics, Pharmacodynamics, and Safety of Ravulizumab in Children and Adolescents With Aquaporin-4 Antibody Positive (AQP4-Ab [+]) Neuromyelitis Optica Spectrum Disorder (NMOSD)PHASE2/PHASE3

ACTIVE_NOT_RECRUITING · via ravulizumab · NCT05346354

A Phase III, Multicenter, Single-Arm Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Adult and Adolescent Patients With Atypical Hemolytic Uremic Syndrome (aHUS)PHASE3

ACTIVE_NOT_RECRUITING · via crovalimab · NCT04861259

A Phase III, Multicenter, Single Arm Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement InhibitionPHASE3

ACTIVE_NOT_RECRUITING · via crovalimab · NCT04654468

A Phase III, Randomized, Open-label, Active-controlled, Multicenter Study Evaluating the Efficacy and Safety of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement InhibitorsPHASE3

ACTIVE_NOT_RECRUITING · via crovalimab · NCT04434092

A Phase III, Randomized, Open-label, Active-controlled, Multicenter Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamic and Efficacy of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement InhibitorsPHASE3

ACTIVE_NOT_RECRUITING · via crovalimab · NCT04432584

HEALEY ALS Platform TrialPHASE2/PHASE3

ACTIVE_NOT_RECRUITING · via zilucoplan · NCT04297683

A Phase II, Open-Label Study of NM8074 in Soliris®-Treated Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)PHASE2

NOT_YET_RECRUITING · via eculizumab · NCT05646563

Clinical Trial on the Use of Ravulizumab in Pregnancies Complicated by Severe Hypertensive DisordersPHASE2

RECRUITING · via ravulizumab · NCT06333652

An Adaptive Phase I/II Study to Assess Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Crovalimab in Healthy Volunteers and Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)PHASE1/PHASE2

ACTIVE_NOT_RECRUITING · via crovalimab · NCT03157635

An Open-Label, Repeated-Dose Assessment of Zilucoplan Concentration in Breast Milk of Healthy Lactating WomenPHASE1

RECRUITING · via zilucoplan · NCT06961747

Phase 4, Single-Arm Study of Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose EculizumabPHASE4

COMPLETED · via eculizumab · NCT04320602

mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Repurposed Drugs (TACTIC-R)PHASE4

UNKNOWN · via ravulizumab · NCT04390464

Multicentric, Prospective Open-label Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With Atypical Hemolytic Uremic Syndrome (aHUS)PHASE4

COMPLETED · via eculizumab · NCT02574403

An Open-Label Multi-Center Study of Eculizumab in Children and Adolescents With a Diagnosis of Paroxysmal Nocturnal HemoglobinuriaPHASE4

COMPLETED · via eculizumab · NCT00867932

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 3 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.

  1. Trial status changed2026-08-12

    A Phase 3, Multicenter, Open-Label Extension Study of Zilucoplan in Subjects With Generalized Myasthenia Gravis

    Status changed to Completed · ClinicalTrials.gov · via zilucoplan

  2. Trial status changed2026-07-21

    HEALEY ALS Platform Trial

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

  3. Label change2026-06-30

    Label change: ECULIZUMAB (BLA125166)

    fda · regulatory · fda · via eculizumab

  4. Supplemental approval2026-06-29

    Supplemental approval: ECULIZUMAB-AAGH (BLA761340)

    fda · regulatory · fda · via eculizumab

  5. Supplemental approval2026-06-29

    Supplemental approval: ECULIZUMAB-AEEB (BLA761333)

    fda · regulatory · fda · via eculizumab

  6. Supplemental approval2026-06-01

    Supplemental approval: ECULIZUMAB (BLA125166)

    fda · regulatory · fda · via eculizumab

  7. Supplemental approval2026-04-28

    Supplemental approval: ECULIZUMAB-AAGH (BLA761340)

    fda · regulatory · fda · via eculizumab

  8. Supplemental approval2026-03-26

    Supplemental approval: ECULIZUMAB-AEEB (BLA761333)

    fda · regulatory · fda · via eculizumab

  9. New publication2020-03-06
    The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment.

    Kidney international · 2020 · 170 citations · Europe PMC · via ravulizumab

  10. New publication2019-03-23
    Eculizumab improves fatigue in refractory generalized myasthenia gravis.

    Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation · 2019 · 42 citations · Europe PMC · via eculizumab

  11. New publication2017-10-20
    Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study.

    The Lancet. Neurology · 2017 · 587 citations · Europe PMC · via eculizumab

  12. New publication2013-11-26
    Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study.

    Ophthalmology · 2014 · 246 citations · Europe PMC · via eculizumab

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.