ABCA1

ATP-binding cassette transporter A1

Score: 0.644 Price: $0.64 Medium Druggability Status: active Wiki: ABCA1

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

317

DEBATES

3D Protein Structure

🧬 ABCA1 — PDB 7QS7 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.47

Clinical Stage

Approved

Target Class

Transporter

Safety

0.50

Druggability Analysis

Drug Development0.75

Structural Tractability0.70

Target Class0.70

Safety Profile0.50

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (1 compounds)

1 Approved

Therapeutic Areas:

Alzheimer's disease and neurodegeneration Dyslipidemia and cardiovascular disease Cognitive decline Amyloid-β clearance disorders Brain cholesterol homeostasis

Druggability Rationale: ABCA1 demonstrates high druggability (0.90 score) due to extensive structural characterization (7 PDB structures at 3.1Å resolution, cryo-EM data, AlphaFold model), validated by Probucol's clinical approval for hypercholesterolemia. As an ABC transporter with well-defined nucleotide-binding domains and transmembrane architecture, it presents multiple tractable binding sites for small molecule modulators to enhance cholesterol efflux activity.

Mechanism: Small molecule modulators to enhance cholesterol efflux and HDL formation

Drug Pipeline (1 compounds)

1 Approved

Known Drugs:

Probucol (approved) — Hypercholesterolemia

Structural Data:

PDB (7) ✓AlphaFold ✓Cryo-EM ✓

5XJY 7ROQ 7TBW 7TBY 7TBZ+2 more

UniProt: A5D8U6

Binding Pocket Analysis:

ABCA1 contains two nucleotide-binding domains (NBDs) that coordinate ATP binding and hydrolysis to drive conformational changes in the transmembrane domains, along with potential allosteric pockets accessible to small molecule modulators. The high-resolution structural data reveals the ATP-binding site and ligand-induced conformational dynamics critical for substrate recognition and cholesterol efflux activation.

🧬 3D Protein Structure

🧬 ABCA1 — PDB 7QS7 Click to expand interactive 3D viewer

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

ABCA1 selectivity is achievable given its unique tissue expression pattern (particularly high in macrophages, enterocytes, and microglia) and distinct substrate specificity for apoA-I; however, off-target activity against other ABC transporters (ABCG1, ABCG4) must be carefully monitored as they share overlapping functions in lipid homeostasis and neuroinflammation.