CX3CR1

C-X3-C Motif Chemokine Receptor 1

Score: 0.593 Price: $0.59 Low Druggability Status: active Wiki: CX3CR1

🔥 Neuroinflammation 🧠 Neurodegeneration

HYPOTHESES

12

PAPERS

25

KG EDGES

602

DEBATES

1

3D Protein Structure

🧬 CX3CR1 — PDB 5UIW Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.44

Clinical Stage

Phase II

Target Class

Gpcr

Safety

0.50

Druggability Analysis

Drug Development0.40

Structural Tractability0.70

Target Class0.85

Safety Profile0.50

Key Metrics

PDB Structures:

2

Known Drugs:

2

Approved:

0

In Clinical Trials:

2

Drug Pipeline (2 compounds)

1 Phase II · 1 Phase I

Druggability Rationale: CX3CR1 demonstrates moderate druggability (0.60) as a GPCR with established structural validation (2.8 Å resolution, 2 PDB structures) and two clinical-stage antagonists (AZD8797 in Phase 2, JNJ-39758979 in Phase 1). However, the GPCR class presents typical challenges including G-protein coupling selectivity and potential off-target cardiovascular effects that have historically complicated GPCR drug development.

Mechanism: GPCR antagonist modulating microglial activation and neuroinflammation

Drug Pipeline (2 compounds)

1 Phase II · 1 Phase I

Known Drugs:

AZD8797 (phase_2) — COPD

JNJ-39758979 (phase_1) — atherosclerosis

Structural Data:

PDB (2) ✓AlphaFold ✓Cryo-EM ✓

UniProt: P49238

🧬 3D Protein Structure

🧬 CX3CR1 — PDB 5UIW Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

CX3CR1 selectivity against other chemokine receptors (particularly CX3CR1 homologs and closely-related GPCRs like CCR5, CXCR4) represents a key challenge. The microglial-restricted expression pattern provides some inherent selectivity advantage, though systemic GPCR off-target binding remains a concern for peripherally-active antagonists.

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 (7)

Relevant trials from ClinicalTrials.gov

Active

0

Completed

4

Total Enrollment

310

By Phase

PHASE1: 3 · PHASE2: 4

A Study of the Safety and Effectiveness of JNJ-39758979 in the Treatment of Adults With Persistent Asthma Completed

PHASE2 NCT00946569 n=116

Asthma

Interventions: JNJ39758979, Placebo

Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L | Started: 2009-08

A Study to Investigate How JNJ-39758979 May Affect the Plasma Levels of Methotrexate in Rheumatoid Arthritis Participant Completed

PHASE1 NCT01442545 n=21

Rheumatoid Arthritis

Interventions: JNJ-39758979 / MTX

Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L | Started: 2011-08

Single and Multiple Dose Study to Explore the Safety and Pharmacokinetics of JNJ-39758979 In Healthy Male Volunteers of Completed

PHASE1 NCT01081821 n=61

Healthy

Interventions: single dose NJ-39758979/ matching placeb, multi-dose JNJ-39758979 /matching placeb

Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L | Started: 2010-02

A Study To Investigate The Effect of JNJ-39758979 on Histamine Induced Itch in Healthy Male Volunteers Completed

PHASE1 NCT01068223 n=24

Histamine Induced Itch

Interventions: A:JNJ-39758979/Placebo #1, C:Cetirizine/JNJ-39758979 Matching Place, B: JNJ-39758979 Matching Placebo /Placeb

Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L | Started: 2010-02

A Study of JNJ-39758979 in Adult Japanese Patients With Moderate Atopic Dermatitis Terminated

PHASE2 NCT01497119 n=88

Dermatitis, Atopic

Interventions: JNJ-39758979, 300 mg, JNJ-39758979, 100 mg, Placebo

Sponsor: Janssen Pharmaceutical K.K. | Started: 2011-10

A Dose Range Finding Study of JNJ-39758979 in Patients With Active Rheumatoid Arthritis Currently Treated With Methotrex Withdrawn

PHASE2 NCT01480388

Active Rheumatoid Arthritis; Rheumatoid

Interventions: Placebo/JNJ-39758979 (300 mg/d), JNJ-39758979 (10 mg), JNJ-39758979 (30 mg)

Sponsor: Janssen Research & Development, LLC | Started: 2011-12

Study of JNJ-39758979 in Symptomatic Adult Patients With Uncontrolled Asthma Withdrawn

PHASE2 NCT01493882

Asthma

Interventions: Placebo, JNJ-39758979 30 mg/d, JNJ-39758979 100 mg/d

Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L | Started: 2012-03

Linked Hypotheses (8)

Optogenetic Microglial Deactivation via Engineered Inhibitory Opsins0.655

CX3CR1 Promoter Methylation Disrupts Neuron-Microglia Cross-Talk0.649

CX3CR1 Agonism Enhances Microglial Phagocytosis of Extracellular Tau Seeds, Preventing Template-Depe0.630

Stratified falsifiers should govern Microglial Priming as Upstream Causal Node Across AD, PD, ALS, M0.591

Fractalkine Axis Amplification via CX3CR1 Positive Allosteric Modulators0.563

CX3CR1 PET with Nano-bodies for Microglial Surveillance State Mapping0.477

Spinal Cord Microglia Activation State Convergence0.455

Microglia-Mediated Synaptic Pruning Modulation to Optimize Functional Connectome Efficiency0.380

Linked Experiments (1)

Proposed experiment from debate on Synaptic pruning by microglia in early AD0.400

Scoring Dimensions

Knowledge Graph (20)

activates (1)

co discussed (16)

BMAL1→CX3CR1HCRTR2→CX3CR1CLOCK→CX3CR1BDNF→CX3CR1AQP4→CX3CR1

▸ Show 11 more

MTNR1A→CX3CR1CX3CR1→HCRTCX3CR1→CACNA1GCX3CR1→ADORA2ACX3CR1→ADRA2AHK2→CX3CR1TREM2→CX3CR1P2RY12→CX3CR1C1Q→CX3CR1C1QA→CX3CR1ANXA1→CX3CR1

regulates (3)

CX3CR1→C1QCX3CR1→CD47CX3CR1→OVERVIEW

Debate History (1)

Should CX3CR1 (C-X3-C Motif Chemokine Receptor 1) be prioritized as a therapeuti2026-04-21