C1QA

Complement C1q A Chain

Score: 0.580 Price: $0.58 Low Druggability Status: active Wiki: C1QA

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

193

DEBATES

3D Protein Structure

🧬 C1QA — PDB 1PK6 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.41

Clinical Stage

Phase II

Target Class

Signaling Protein

Safety

0.45

Druggability Analysis

Drug Development0.35

Structural Tractability0.70

Target Class0.50

Safety Profile0.45

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (1 compounds)

1 Phase II

Therapeutic Areas:

Alzheimer's disease and neurodegeneration Neuroinflammation Synaptic dysfunction and synaptopathy Microglial activation disorders Complement-mediated neurological diseases Multiple sclerosis Traumatic brain injury

Druggability Rationale: C1QA demonstrates medium druggability (0.55) supported by strong structural data (4 PDB structures at 1.25 Å resolution, AlphaFold and cryo-EM availability) and clinical validation via ANX005 in Phase 2 trials. However, as a secreted signaling protein component of the C1 complex, it is inherently challenging to drug with small molecules, favoring antibody-based or protein-based therapeutic modalities over traditional ligand approaches.

Mechanism: Complement cascade inhibitor or antibody-mediated neutralization

Drug Pipeline (1 compounds)

1 Phase II

Known Drugs:

ANX005 (phase_2) — complement-mediated diseases

Structural Data:

PDB (4) ✓AlphaFold ✓Cryo-EM ✓

5HBA 5HKJ 5HZF 6Z6V

UniProt: A0A8Q3SI59

Binding Pocket Analysis:

C1QA lacks a traditional small-molecule binding pocket; instead, therapeutic engagement occurs through antibody epitope recognition or protein-protein interaction interfaces within the C1 complex. The collagen-like domain and globular head region (characterized by the high-resolution structures) serve as primary interaction sites for antibody binding and C1r/C1s recruitment rather than small-molecule ligand binding.

🧬 3D Protein Structure

🧬 C1QA — PDB 1PK6 Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

C1QA selectivity is primarily a concern at the pathway level rather than isoform level, as antibody-mediated approaches (like ANX005) must distinguish between C1q and related complement components (C1r, C1s) to avoid unintended pathway inhibition. Off-target risks include broader complement system suppression affecting immune homeostasis and infection susceptibility.