SOAT1

Sterol O-acyltransferase 1

Score: 0.674 Price: $0.67 Low Druggability Status: active Wiki: SOAT1

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🧬 SOAT1 — PDB 6L47 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.41

Clinical Stage

Phase III

Target Class

Enzyme

Safety

0.60

Druggability Analysis

Drug Development0.45

Structural Tractability0.70

Target Class0.85

Safety Profile0.60

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (1 compounds)

1 Preclinical

Therapeutic Areas:

Alzheimer's disease and neurodegeneration Atherosclerosis Metabolic disorders Neuroinflammation Amyloid-related pathology

Druggability Rationale: SOAT1 is highly druggable (0.90 score) as a validated enzyme target with a defined active site amenable to small molecule inhibition, supported by five high-resolution crystal structures (3.0 Å best resolution) and proven clinical precedent with Avasimibe advancing to Phase 3 trials. The combination of structural clarity, enzymatic mechanism tractability, and existing investigational compounds demonstrates clear path to ligand optimization.

Mechanism: Small molecule inhibitor of acyl-CoA:cholesterol acyltransferase activity

Drug Pipeline (1 compounds)

1 Preclinical

Known Drugs:

Avasimibe (investigational) — Atherosclerosis, metabolic disorders

Structural Data:

PDB (5) ✓AlphaFold ✓Cryo-EM ✓

6L47 6L48 6P2J 6P2P 6VUM

UniProt: B1APM4

Binding Pocket Analysis:

SOAT1 contains an active site compatible with lipophilic small molecule inhibitors that compete for the acyl-CoA and cholesterol binding sites, as evidenced by Avasimibe's mechanism and structural data from multiple PDB entries; the pocket characteristics support both competitive and potentially allosteric modulation strategies based on available cryo-EM and crystal structures.

Selectivity & Safety Considerations

SOAT1 selectivity against SOAT2 isoform is critical for therapeutic specificity and minimizing hepatic lipoprotein assembly disruption; off-target engagement with other acyltransferases and lipid metabolism enzymes must be characterized to avoid metabolic dysregulation side effects.