C1Q

Complement C1q

Score: 0.586 Price: $0.59 Low Druggability Status: active Wiki: C1Q

🧠 Neurodegeneration

HYPOTHESES

58

PAPERS

22

KG EDGES

1361

DEBATES

1

3D Protein Structure

🧬 C1Q — PDB 1PK6 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.36

Clinical Stage

Approved

Target Class

Signaling Protein

Safety

0.45

Druggability Analysis

Drug Development0.75

Structural Tractability0.30

Target Class0.50

Safety Profile0.45

Key Metrics

PDB Structures:

0

Known Drugs:

1

Approved:

1

In Clinical Trials:

0

Drug Pipeline (1 compounds)

1 Approved

Druggability Rationale: C1Q demonstrates medium druggability (0.55) supported by the clinical success of Sutimlimab, an approved monoclonal antibody, validating the target for therapeutic intervention. As a secreted signaling protein in the complement cascade, C1Q is inherently druggable via antibody-mediated neutralization, though small-molecule inhibitors face challenges due to the lack of a classical ATP-binding pocket and the protein's structural complexity.

Mechanism: Complement cascade inhibitor or antibody-mediated neutralization

Drug Pipeline (1 compounds)

1 Approved

Known Drugs:

Sutimlimab (approved) — Cold agglutinin disease

Structural Data:

PDB —AlphaFold ✓Cryo-EM ✓

🧬 3D Protein Structure

🧬 C1Q — PDB 1PK6 Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selectivity is a critical challenge given C1Q's central role in both pathological complement activation and physiological immune homeostasis; therapeutic targeting must preserve beneficial functions (pathogen clearance, apoptotic cell clearance) while blocking aberrant neuroinflammatory signaling. Antibody-based approaches offer superior selectivity through epitope selection, whereas pan-complement inhibitors risk broad immunosuppression.

Clinical Trials (4)

Relevant trials from ClinicalTrials.gov

Active

1

Completed

3

Total Enrollment

473

By Phase

PHASE3: 3 · Unknown: 1

Cold Agglutinin Disease Real World Evidence Registry Recruiting

Unknown NCT05791708 n=400

Cold Agglutinin Disease (CAD), Cold Agglutinin Syndrome (CAS)

Interventions: Sutimlimab

Sponsor: RECORDATI GROUP | Started: 2019-12-12

A Study to Assess the Efficacy and Safety of BIVV009 (Sutimlimab) in Participants With Primary Cold Agglutinin Disease W Completed

PHASE3 NCT03347396 n=24

Agglutinin Disease, Cold

Interventions: BIVV009

Sponsor: Bioverativ, a Sanofi company | Started: 2018-03-05

A Study to Assess the Efficacy and Safety of BIVV009 (Sutimlimab) in Participants With Primary Cold Agglutinin Disease W Completed

PHASE3 NCT03347422 n=42

Cold Agglutinin Disease

Interventions: sutimlimab (BIVV009), placebo

Sponsor: Bioverativ, a Sanofi company | Started: 2018-03-17

Sutimlimab (BIVV009) for the Adult Participants With Cold Agglutinin Disease (CAD) Who Have Completed Phase 3 Studies (C Completed

PHASE3 NCT05132127 n=7

Cold Agglutinin Disease

Interventions: sutimlimab

Sponsor: Sanofi | Started: 2021-11-11

Linked Hypotheses (10)

Complement C1q-Mediated Synaptic Pruning Drives Early Cognitive Decline in Alzheimer's Disease0.769

NFκB/C1Q SASP Modulation for Synaptic Protection0.534

Tripartite Synapse Cell Type-Nonautonomous Crosstalk: Coordinated Failure0.510

Microglial SPI1 Priming by Circulating C1Q0.455

C1q-Alectinib Complexation Facilitates Brain Penetration via Receptor-Mediated Transcytosis0.161

Direct C1q Binding Enables FcγR-Independent Complement Activation on Tumor Cells0.148

Human Serum Albumin-Mediated Displacement Creates False-Positive C1q Binding Signals0.132

C1q Binding Reflects Broader Kinase Inhibitor Promiscuity Rather Than Specific Complement Targeting0.124

Alectinib Binds Mitochondrial C1q-like Proteins (C1QDC1) Rather Than Circulating C1q0.122

C1q Binding Analysis Across ALK Inhibitor Chemical Series Would Resolve Specificity0.115

Linked Experiments (2)

Bidirectional Mendelian randomization analysis of C1Q and ischemic stroke0.900

Bidirectional Mendelian randomization analysis of C1Q and ischemic stroke0.900

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

C1Q→neurodegeneration

co discussed (17)

MMP9→C1QSLC7A11→C1QAQP4→C1QCD38→C1QC1Q→NAMPT

▸ Show 12 more

C1Q→GPX4C1Q→PLA2G6C1Q→MMP2C1Q→C3C1Q→PLA2G4ACGAS→C1QC1Q→IL1BC1Q→DNASE2C1Q→STING1HK2→C1QTREM2→C1QP2RY12→C1Q

interacts with (2)

C1Q→C3C3→C1Q

Debate History (1)

Should C1Q (Complement C1q) be prioritized as a therapeutic target for neurodege2026-04-21