Druggability & Clinical Context
Druggability
Medium
Score: 0.50
Druggability Analysis
Structural Tractability0.95
Key Metrics
PDB Structures:
130
Known Drugs:
1
Approved:
0
In Clinical Trials:
1
Drug Pipeline (1 compounds)
Druggability Rationale: VCP is highly druggable (0.75 score) due to its well-characterized ATPase active site, extensive structural data (130+ PDB entries at 1.55 Å resolution), and proven precedent with CB-5083 advancing to clinical trials. The enzyme's defined nucleotide-binding pocket and accessibility to small-molecule inhibitors make it an excellent target for competitive ATP-site binders affecting protein quality control pathways.
Mechanism: Small molecule inhibitors of VCP ATPase activity affecting protein quality control
Drug Pipeline (1 compounds)
Known Drugs:CB-5083 (phase1) — Cancer (neurodegenerative applications explored)
Structural Data:PDB (130) ✓AlphaFold ✓Cryo-EM ✓
Selectivity & Safety Considerations
VCP selectivity is moderately challenging due to AAA+ ATPase family homology (p97/VCP orthologs, NSF, other AAA-ATPases), requiring structural selectivity through the D1/D2 domain architecture or allosteric modulation to minimize off-target effects on related ATPases. Isoform selectivity is less of a concern as VCP lacks major splice variants, but tissue distribution and functional context differences necessitate careful pharmacodynamic assessment.
Clinical Trials (4)
Relevant trials from ClinicalTrials.gov
By Phase
PHASE1: 2 · Unknown: 2
Unknown
NCT01353430
n=50
Inclusion Body Myopathy With Early-onset, Paget Disease of Bone, Frontotemporal Dementia
Sponsor: University of California, Irvine | Started: 2007-11-15
Unknown
NCT04823143
n=44
IBMPFD
Sponsor: Nationwide Children's Hospital | Started: 2021-03-18
PHASE1
NCT02223598
n=120
Lymphoid Hematological Malignancies, Relapsed and Refractory Multiple Myeloma
Interventions: CB-5083, Dexamethasone
Sponsor: Cleave Biosciences, Inc. | Started: 2014-08-25
PHASE1
NCT02243917
n=62
Advanced Solid Tumors
Interventions: CB-5083
Sponsor: Cleave Biosciences, Inc. | Started: 2014-10-11