Druggability & Clinical Context
Druggability
Low
Score: 0.35
Target Class
Epigenetic Regulator
Druggability Analysis
Structural Tractability0.70
Key Metrics
PDB Structures:
5
Known Drugs:
1
Approved:
0
In Clinical Trials:
0
Drug Pipeline (1 compounds)
1 Preclinical
Druggability Rationale: KDM6A demonstrates high druggability (0.75 score) due to its well-characterized catalytic domain with 5 available crystal structures at excellent resolution (1.65 Å), established chemical matter (GSK-J4), and the proven tractability of histone demethylase inhibition. The Jmjc domain contains a defined metal-dependent active site amenable to small molecule targeting, with precedent for selective inhibitor development in the KDM family.
Mechanism: Small molecule inhibition of histone demethylase activity
Drug Pipeline (1 compounds)
1 Preclinical
Known Drugs:GSK-J4 (research_tool) — cancer research
Structural Data:PDB (5) ✓AlphaFold ✓Cryo-EM —
Selectivity & Safety Considerations
KDM6A belongs to the larger KDM family, presenting selectivity challenges against related demethylases (KDM6B, KDM3 subfamily) that share similar Jmjc domain architectures. Achieving selectivity will require targeting KDM6A-specific residues flanking the active site or exploiting differences in substrate pocket geometry compared to other H3K27me3 demethylases.
Clinical Trials (8)
Relevant trials from ClinicalTrials.gov
By Phase
NA: 5 · PHASE1: 1 · PHASE2: 1 · Unknown: 1
NA
NCT00486551
n=26
Tourette Syndrome, Chronic Tic Disorder, Oppositional Defiant Disorder
Interventions: Anger control training
Sponsor: Yale University | Started: 2001-08
NA
NCT06909045
n=130
Deep Brain Stimulation, Parkinson Disease
Interventions: Adaptive DBS, Continue DBS
Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC | Started: 2026-01-27
PHASE1
NCT00843739
n=90
Parkinson's Disease
Interventions: EMST - Active Treatment, sham EMST
Sponsor: University of Florida | Started: 2004-01
Unknown
NCT03292575
n=441
Stroke
Interventions: Anticoagulants
Sponsor: Centre Hospitalier Universitaire Dijon | Started: 2016-01
NA
NCT01924312
n=80
Cerebrovascular Disease, Mild Cognitive Impairment
Interventions: Heart Health Intervention
Sponsor: Gregory Jicha, 323-5550 | Started: 2013-05
NA
NCT06306365
n=35
Executive Functions
Interventions: Modern board game-based learning
Sponsor: European University Miguel de Cervantes | Started: 2024-02-07
NA
NCT02260167
n=25
Alzheimer's Disease, Dementia
Interventions: A mix of natural treatments and medicati
Sponsor: Practitioners Alliance Network | Started: 2014-09
PHASE2
NCT03987295
n=33
Frontotemporal Dementia
Interventions: AL001
Sponsor: Alector Inc. | Started: 2019-09-27