C3

Complement C3

Score: 0.716 Price: $0.72 Medium Druggability Status: active Wiki: C3

🧠 Neurodegeneration

HYPOTHESES

145

PAPERS

KG EDGES

7190

DEBATES

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:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (2 compounds)

1 Approved · 1 Phase III

Therapeutic Areas:

Paroxysmal nocturnal hemoglobinuria (PNH) Geographic atrophy (age-related macular degeneration) Alzheimer's disease Neuroinflammation and neurodegeneration C3 glomerulopathy Post-stroke neuroprotection Traumatic brain injury

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

Binding Pocket Analysis:

C3 contains a thioester-containing pocket critical for covalent bond formation during complement activation, as well as convertase binding interfaces exploitable by small molecule inhibitors targeting the C3a/C3b conversion step. High-resolution structural data (1.7Å) and AlphaFold predictions enable structure-based drug design targeting these allosteric and active-site regulatory mechanisms.

🧬 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.