Protein / target

Complement C3

Encoded byC3P01024Homo sapiensSwiss-Prot

UniProt: P01024 Ensembl: ENSG00000125730 HGNC: HGNC:1318 NCBI Gene: 718

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

View by indication →

Clinical trials

Small-molecule tractable

Druggability

Structure with Ligand

Protein at a glance

Biological role

C5L2 anaphylatoxin chemotactic receptor binding

Strongest disease association

Macular Degeneration

Via encoding gene C3 · Genetic evidence · score 0.91

Therapeutic position

Established drug target

Research activity

Emerging research

5 papers · latest 2024

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 non-enzymatic components of the classical, alternative, lectin and GZMK 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

Subcellular location

SecretedCell surface

Domains and Gene Ontology detail (42)

Domains & features

Anaphylatoxin-likeNTR

Gene Ontology

Cazurophil granule lumen
Cblood microparticle
Ccell surface
Cendoplasmic reticulum lumen
Cextracellular exosome
Cextracellular region
Cextracellular space
Cplasma membrane
Cprotein-containing complex
Csecretory granule lumen
FC5L2 anaphylatoxin chemotactic receptor binding
Fendopeptidase inhibitor activity

1663 aa · 187 kDa

Biological roles

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

Lipid & lipoprotein metabolismGOSynaptic signallingGOImmune signallingGOG protein-coupled signallingGO

View supporting evidence

Lipid & lipoprotein metabolism

·fatty acid metabolic process
·regulation of triglyceride biosynthetic process

Synaptic signalling

·complement-mediated synapse pruning

Immune signalling

·B cell activation
·immune response
·inflammatory response

G protein-coupled signalling

·G protein-coupled receptor signaling pathway
·positive regulation of G protein-coupled receptor signaling pathway

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

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.

Eye Diseases1 medicine

pegcetacoplan

Hemoglobinuria, Paroxysmal1 medicine

pegcetacoplan

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

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.

pegcetacoplan

Narrow target profileApprovedInhibitor

Complement C3 inhibitor

Indicated for Eye Diseases, Hemoglobinuria, Paroxysmal

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 C3

Gene-level evidence surfaced through the gene C3 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.

Macular Degeneration

0.95Well supported

Genetic evidence dominant · Open Targets 0.72

Retinal Diseases

0.89Well supported

Genetic evidence dominant · Open Targets 0.54

View evidence synthesis (2)

Macular DegenerationWell supported

0.95

agreement 0.85–1.00

Genetic62%Clinical29%Literature9%Genetic literaturedup

Open Targets aggregate 0.72 · 3 independent evidence families · 1 not counted as duplicate

Retinal DiseasesWell supported

0.89

agreement 0.75–1.00

Genetic98%Literature2%

Open Targets aggregate 0.54 · 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

Macular Degeneration0.72

Retinal Diseases0.54

Drug development

3 compounds recorded · 1 approved · 2 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 (3)

PEGCETACOPLANApproval

AL-78898APhase 2

AMY-101Phase 2

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 pocket) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

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

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 (9)

SM · Structure with LigandSM · High-Quality PocketAB · 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.

Safety-related annotations

fasting triglyceride levels and susceptibility to metabolic syndromeClinPGxfasting triglyceride levelsClinPGx

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

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.

An Open-Label, Nonrandomized, Multicenter Extension Study to Evaluate the Long-term Safety and Efficacy of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative GlomerulonephritisPHASE3

ACTIVE_NOT_RECRUITING · via pegcetacoplan · NCT05809531

A Phase I/II Study of Complement Inhibition in Pancreatic Ductal AdenocarcinomaPHASE1/PHASE2

RECRUITING · via pegcetacoplan · NCT07214298

Safety, Tolerability, Pharmacokinetics, and Exploratory Efficacy of ABBV-6628 in Subjects With Geographic Atrophy Secondary to Age-Related Macular DegenerationPHASE1/PHASE2

RECRUITING · via pegcetacoplan · NCT07160179

Randomized, Double-masked, Active-controlled, Multicenter Study to Evaluate Efficacy and Safety of Two Regimens of Intravitreal BI 771716 Against Pegcetacoplan in Participants With Geographic Atrophy Secondary to Age-related Macular Degeneration VERDANT TrialPHASE2

ACTIVE_NOT_RECRUITING · via pegcetacoplan · NCT06722157

View all trials (19)

Randomized Phase 2 Trial of APL-2 With Pembrolizumab vs. APL-2 With Pembrolizumab and Bevacizumab vs. Bevacizumab Alone in Patients With Recurrent Ovarian Cancer and Persistent Malignant EffusionPHASE2

RECRUITING · via pegcetacoplan · NCT04919629

An Open Label, Single-Arm, Phase 2 Study to Evaluate the Safety, Pharmacokinetics, and Biologic Activity of Pegcetacoplan in Pediatric Patients With Paroxysmal Nocturnal HemoglobinuriaPHASE2

RECRUITING · via pegcetacoplan · NCT04901936

Safely Quenching Complement in Stroke Subjects: A Phase 1 Safety TrialPHASE1

NOT_YET_RECRUITING · via pegcetacoplan · NCT07495722

A Phase 3, Randomized, Placebo-Controlled, Double-Blinded, Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Adults at High Risk of Delayed Graft Function (DGF) Following Kidney Allograft TransplantationPHASE3

SUSPENDED · via pegcetacoplan · NCT07020832

A Phase 3, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Cold Agglutinin Disease (CAD)PHASE3

COMPLETED · via pegcetacoplan · NCT05096403

A Phase 3, Randomized, Placebo-Controlled, Double-Blinded, Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative GlomerulonephritisPHASE3

COMPLETED · via pegcetacoplan · NCT05067127

A Phase 3, Open-Label, Multicenter, Extension Study to Evaluate the Long-Term Safety and Efficacy of Pegcetacoplan in Subjects With Geographic Atrophy Secondary to Age-Related Macular DegenerationPHASE3

COMPLETED · via pegcetacoplan · NCT04770545

An Open Label, Non-Randomized, Multi-Center Extension Study to Evaluate the Long-Term Safety and Efficacy of Pegcetacoplan in the Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH)PHASE3

COMPLETED · via pegcetacoplan · NCT03531255

A Phase III, Randomized, Multi-Center, Open-Label, Active-Comparator Controlled Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)PHASE3

COMPLETED · via pegcetacoplan · NCT03500549

An Open-label, Single-arm, Multicenter Pilot Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Efficacy and Safety of Pegcetacoplan in Patients With Transplant-associated Thrombotic Microangiopathy (TA-TMA) After Hematopoietic Stem Cell Transplantation (HSCT)PHASE2

COMPLETED · via pegcetacoplan · NCT05148299

An Open-Label, Randomized, Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of Pegcetacoplan in the Treatment of Post-Transplant Recurrence of C3G or IC-MPGNPHASE2

COMPLETED · via pegcetacoplan · NCT04572854

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Subjects With Amyotrophic Lateral Sclerosis (ALS)PHASE2

TERMINATED · via pegcetacoplan · NCT04579666

Phase IIa, Open Label, Multiple Dose Study to Assess the Safety, Efficacy and Pharmacokinetics of Subcutaneously Administered APL-2 in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH).PHASE2

COMPLETED · via pegcetacoplan · NCT03593200

An 18-Month Phase Ib/II Multi-Center, Open Label Study to Evaluate the Safety of Intravitreal APL-2 Therapy in Patients With Neovascular Age-Related Macular Degeneration (AMD)PHASE1/PHASE2

TERMINATED · via pegcetacoplan · NCT03465709

A Phase II, Multicenter, Randomized, Single-Masked, Sham-Controlled Study of Safety, Tolerability and Evidence of Activity of Intravitreal APL-2 Therapy in Patients With Geographic Atrophy (GA)PHASE2

COMPLETED · via pegcetacoplan · NCT02503332

A 24-Month Phase Ib Multi-Center, Open Label, Single Arm Study to Evaluate the Safety of Intravitreal APL-2 Therapy in Patients Diagnosed With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)PHASE1

COMPLETED · via pegcetacoplan · NCT03777332

A Phase Ib, Open Label, Multiple Ascending Dose, Pilot Study to Assess the Safety, Preliminary Efficacy and Pharmacokinetics of Subcutaneously Administered APL-2 in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH)PHASE1

COMPLETED · via pegcetacoplan · NCT02588833

An Open Label, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of APL-2 as an Add-On to Standard of Care in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH).PHASE1

COMPLETED · via pegcetacoplan · NCT02264639

Assessment of Safety, Tolerability and Pharmacokinetics of Intravitreal APL-2 Therapy for Neovascular Age-Related Macular Degeneration (AMD)PHASE1

COMPLETED · via pegcetacoplan · NCT02461771

ClinicalTrials.gov via the drug-target graph.

What's happening now

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.

Indication expanded2026-08-20
Indication expansion: PEGCETACOPLAN (NDA215014)
fda · regulatory · fda · via pegcetacoplan
Indication expanded2025-07-28
Indication expansion: PEGCETACOPLAN (NDA215014)
fda · regulatory · fda · via pegcetacoplan
Label change2025-06-10
Label change: PEGCETACOPLAN (NDA215014)
fda · regulatory · fda · via pegcetacoplan
Supplemental approval2024-10-07
Supplemental approval: PEGCETACOPLAN (NDA215014)
fda · regulatory · fda · via pegcetacoplan
Label change2024-02-08
Label change: PEGCETACOPLAN (NDA215014)
fda · regulatory · fda · via pegcetacoplan
Label change2023-09-28
Label change: PEGCETACOPLAN (NDA215014)
fda · regulatory · fda · via pegcetacoplan
Indication expanded2023-02-08
Indication expansion: PEGCETACOPLAN (NDA215014)
fda · regulatory · fda · via pegcetacoplan
Regulatory approval2021-12-13
Approval: Aspaveli (EMA)
ema · regulatory · ema · via pegcetacoplan
Regulatory approval2021-05-14
Approval: PEGCETACOPLAN (NDA215014)
fda · regulatory · fda · via pegcetacoplan

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.