C3

Complement C3

Score: 0.667 Price: $0.67 Medium Druggability Status: active Wiki: C3

🧠 Neurodegeneration

HYPOTHESES

145

PAPERS

22

KG EDGES

7190

DEBATES

1

3D Protein Structure

🧬 C3 — PDB 2A73 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.50

Clinical Stage

Approved

Target Class

Signaling Protein

Safety

0.40

Druggability Analysis

Drug Development0.80

Structural Tractability0.85

Target Class0.50

Safety Profile0.40

Key Metrics

PDB Structures:

33

Known Drugs:

2

Approved:

1

In Clinical Trials:

1

Drug Pipeline (2 compounds)

1 Approved · 1 Phase III

Druggability Rationale: C3 is highly druggable (0.75 score) due to its well-characterized structure with 33 PDB entries at 1.7Å resolution, enabling rational drug design of small molecule convertase inhibitors. The existence of approved (Pegcetacoplan) and phase-3 (APL-2) therapeutics validates the target's clinical tractability, though pegcetacoplan's peptide nature suggests alternative modalities may complement small molecule approaches.

Mechanism: Small molecule inhibitor of complement activation or convertase activity

Drug Pipeline (2 compounds)

1 Approved · 1 Phase III

Known Drugs:

Pegcetacoplan (approved) — Paroxysmal nocturnal hemoglobinuria

APL-2 (phase_3) — Geographic atrophy

Structural Data:

PDB (33) ✓AlphaFold ✓Cryo-EM ✓

2A78 2A9K 2GOX 2NOJ 3BW8+28 more

UniProt: P01024

🧬 3D Protein Structure

🧬 C3 — PDB 2A73 Click to expand interactive 3D viewer

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

C3 selectivity is advantageous since it targets the central hub of complement activation, but inhibition may lack isoform selectivity due to structural conservation across complement proteins. Off-target risk includes potential disruption of legitimate immune complement responses needed for pathogen clearance and homeostasis, necessitating careful dosing and patient monitoring.

3D Protein Structure

PDB: Open in RCSB AlphaFold model

Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.

Clinical Trials (8)

Relevant trials from ClinicalTrials.gov

Active

3

Completed

5

Total Enrollment

2,000

By Phase

PHASE1: 1 · PHASE2: 3 · PHASE3: 3 · Unknown: 1

A Phase 3 Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Adults at High Risk of Delayed Graft Function (D Recruiting

PHASE3 NCT07020832 n=320

Delayed Graft Function, End Stage Renal Disease, Deceased Donor Kidney Transplant

Interventions: Pegcetacoplan, Placebo

Sponsor: Apellis Pharmaceuticals, Inc. | Started: 2026-02

A Real World Effectiveness Study of Pegcetacoplan in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Recruiting

Unknown NCT05776472 n=200

Paroxysmal Nocturnal Hemoglobinuria

Interventions: Pegcetacoplan

Sponsor: Swedish Orphan Biovitrum | Started: 2023-06-26

Study Assessing the Safety and Efficacy of Pegcetacoplan in Post-Transplant Recurrence of C3G or IC-MPGN Active Not Recruiting

PHASE2 NCT04572854 n=13

C3G, IC-MPGN, Renal Transplant

Interventions: Pegcetacoplan

Sponsor: Apellis Pharmaceuticals, Inc. | Started: 2021-09-07

A Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographi Completed

PHASE3 NCT03525613 n=637

Geographic Atrophy

Interventions: APL-2, APL-2, Sham Procedure

Sponsor: Apellis Pharmaceuticals, Inc. | Started: 2018-08-31

An Extension Study to Evaluate the Long-term Safety and Efficacy of Pegcetacoplan (APL-2) in Subjects With Geographic At Completed

PHASE3 NCT04770545 n=792

Geographic Atrophy Secondary to Age-rela

Interventions: PEGCETACOPLAN (APL-2)

Sponsor: Apellis Pharmaceuticals, Inc. | Started: 2021-03-04

Phase II Study Assessing Safety and Efficacy of APL-2 in Glomerulopathies Completed

PHASE2 NCT03453619 n=21

IgA Nephropathy, Lupus Nephritis, Membranous Nephropathy

Interventions: APL-2

Sponsor: Apellis Pharmaceuticals, Inc. | Started: 2018-02-26

A Phase IIa Study to Assess the Safety, Efficacy, and Pharmacokinetics of Subcutaneously Administered Pegcetacoplan (APL Completed

PHASE2 NCT03593200 n=4

PNH

Interventions: Pegcetacoplan

Sponsor: Apellis Pharmaceuticals, Inc. | Started: 2018-08-16

Assessment of Safety, Tolerability and Pharmacokinetics of Intravitreal Pegcetacoplan (APL-2) for Patients With Wet AMD Completed

PHASE1 NCT02461771 n=13

Neovascular Age-Related Macular Degenera

Interventions: Pegcetacoplan

Sponsor: Apellis Pharmaceuticals, Inc. | Started: 2015-01-28

Linked Hypotheses (0)

No linked hypotheses

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

activates (2)

C3→TUMOR_AGGRESSIVENESSPRKCB→C3

associated with (1)

C3→neurodegeneration

co discussed (15)

BMAL1→C3HK2→C3MIRO1→C3P2RY1→C3SOAT1→C3

▸ Show 10 more

KCNK2→C3TET2→C3PIEZO1→C3P2RX7→C3DGAT1→C3MMP9→C3SLC7A11→C3AQP4→C3CD38→C3C1Q→C3

interacts with (2)

C1Q→C3C3→C1Q

Debate History (1)

Should C3 (Complement C3) be prioritized as a therapeutic target for neurodegene2026-04-21