Druggability & Clinical Context
Druggability
Medium
Score: 0.53
Druggability Analysis
Structural Tractability0.70
Key Metrics
PDB Structures:
2
Known Drugs:
3
Approved:
0
In Clinical Trials:
0
Drug Pipeline (3 compounds)
Therapeutic Areas:Alzheimer's disease Cognitive decline/dementia Excitatory neuron degeneration Synaptic dysfunction Age-related neurodegeneration Cognitive aging
Druggability Rationale: SLC17A7 presents significant druggability challenges as a vesicular transporter with no known clinical drugs, a low druggability score (0.35), and limited structural data. Membrane transporters typically require innovative modulation approaches (allosteric modulators, protein stabilizers, or transcriptional activators) rather than conventional orthosteric inhibitors, and the lack of high-resolution structural information further constrains rational drug design.
Mechanism: Expression restoration — upregulating SLC17A7 transcription or stabilizing VGLUT1 protein to preserve excitatory synaptic function
Drug Pipeline (3 compounds)
Known Drugs:Riluzole (Approved (ALS))
Troriluzole (Phase II/III)
Chicago Sky Blue 6B (Tool compound)
Structural Data:PDB (2) ✓AlphaFold ✓Cryo-EM ✓
Binding Pocket Analysis:Structural characterization of SLC17A7 remains incomplete, limiting detailed binding pocket information. VGLUT1 is presumed to contain a glutamate substrate binding site within its transmembrane domain architecture, but allosteric or stabilizing binding sites for small molecules or biologics have not been systematically mapped and represent a key gap for drug design.
Selectivity & Safety Considerations
Selectivity is challenged by the presence of three VGLUT isoforms (VGLUT1, VGLUT2, VGLUT3) with overlapping tissue distribution and sequence homology. However, VGLUT1 predominance in cortical/hippocampal regions offers therapeutic window potential if isoform-selective modulators targeting unique structural elements can be developed.
Clinical Trials (8)
Relevant trials from ClinicalTrials.gov
By Phase
EARLY_PHASE1: 2 · PHASE2: 3 · PHASE3: 3
PHASE3
NCT03127267
n=495
Amyotrophic Lateral Sclerosis
Interventions: Masitinib (6.0), Riluzole, Placebo
Sponsor: AB Science | Started: 2021-02-02
EARLY_PHASE1
NCT06989853
n=40
Methamphetamine Use Disorder
Interventions: Placebo, Methamphetamine
Sponsor: William Stoops | Started: 2025-08-25
EARLY_PHASE1
NCT06552260
n=27
Glioblastoma, Recurrent Glioblastoma, Brain Tumor
Interventions: Troriluzole
Sponsor: Ugonma Chukwueke | Started: 2025-02-19
PHASE3
NCT01257828
n=270
Cervical Spondylotic Myelopathy
Interventions: riluzole, Placebo medication
Sponsor: AOSpine North America Research Network | Started: 2012-03
PHASE3
NCT03829241
n=881
Generalized Anxiety Disorder
Interventions: Troriluzole, Placebo
Sponsor: Biohaven Pharmaceuticals, Inc. | Started: 2019-02-19
PHASE2
NCT00774423
n=141
SMA
Interventions: Riluzole
Sponsor: Assistance Publique - Hôpitaux de Paris | Started: 2006-01
PHASE2
NCT01204918
n=104
Depression
Interventions: Riluzole, placebo
Sponsor: Yale University | Started: 2011-06
PHASE2
NCT03299166
n=426
Obsessive-Compulsive Disorder
Interventions: Troriluzole, Placebo
Sponsor: Biohaven Pharmaceuticals, Inc. | Started: 2017-12-19