Druggability & Clinical Context
Druggability
Medium
Score: 0.47
Druggability Analysis
Structural Tractability0.95
Key Metrics
PDB Structures:
128
Known Drugs:
1
Approved:
0
In Clinical Trials:
0
Drug Pipeline (1 compounds)
1 Preclinical
Druggability Rationale: cGAS demonstrates medium druggability (0.55) with favorable characteristics: it is a well-validated enzyme target with a defined catalytic active site, abundant structural data (128 PDB structures at 1.25 Å resolution), and proof-of-concept inhibition by RU.521 in preclinical studies. However, the moderate druggability score likely reflects challenges in achieving potency and selectivity against related nucleotidyl transferases while maintaining CNS penetration for neuroinflammatory indications.
Mechanism: Small molecule inhibitor of cyclic dinucleotide synthesis
Drug Pipeline (1 compounds)
1 Preclinical
Known Drugs:RU.521 (preclinical) — Autoimmune diseases
Structural Data:PDB (128) ✓AlphaFold ✓Cryo-EM ✓
Selectivity & Safety Considerations
Primary selectivity concern is discrimination from other nucleotidyl transferases (e.g., OAS1, DncV) and ATP synthases that share structural homology in the catalytic domain. Off-target engagement with STING pathway components or innate immune receptors could limit therapeutic window, particularly given cGAS's role in physiological antiviral immunity.
Clinical Trials (4)
Relevant trials from ClinicalTrials.gov
By Phase
PHASE2: 1 · PHASE3: 1 · Unknown: 2
Unknown
NCT00990379
n=45
Parkinson's Disease, HIV Infections
Sponsor: Salena Killion | Started: 2009-04
PHASE3
NCT00488319
n=400
Schizophrenia, Schizophrenic Disorders, Psychotic Disorders
Interventions: Paliperidone ER
Sponsor: Janssen Research & Development, LLC | Started: 2007-06
Unknown
NCT04233099
n=126
Amyotrophic Lateral Sclerosis
Interventions: Raman analysis of saliva with data colle
Sponsor: Fondazione Don Carlo Gnocchi Onlus | Started: 2019-07-01
PHASE2
NCT01519193
n=42
Aggressive Behavior, Post-Traumatic Stress Disorder
Interventions: Narrative Exposure Therapy for violent o
Sponsor: University of Konstanz | Started: 2011-01