ABCB1

P-glycoprotein

Score: 0.587 Price: $0.59 Medium Druggability Status: active Wiki: ABCB1

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

373

DEBATES

3D Protein Structure

🧬 ABCB1 — PDB 6C0V Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.47

Clinical Stage

Phase III

Target Class

Transporter

Safety

0.30

Druggability Analysis

Drug Development0.45

Structural Tractability0.85

Target Class0.70

Safety Profile0.30

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (2 compounds)

2 Preclinical

Therapeutic Areas:

CNS drug delivery enhancement Neurodegenerative diseases (Parkinson's, Alzheimer's) Glioblastoma and CNS malignancies Epilepsy Neuroinflammatory disorders HIV-associated neurocognitive disorder

Druggability Rationale: ABCB1 is highly druggable (0.80 score) due to extensive structural characterization (33 PDB structures, 2.49 Å resolution), well-established binding sites, and successful investigational inhibitors (Tariquidar, Elacridar) demonstrating proof-of-concept. However, as a transporter rather than a typical enzyme, it presents challenges in achieving selective modulation without broad substrate spectrum disruption, though the high clinical trial phase (3) confirms therapeutic viability.

Mechanism: Small molecule inhibitors to reduce efflux pump activity and enhance CNS drug penetration

Drug Pipeline (2 compounds)

2 Preclinical

Known Drugs:

Tariquidar (investigational) — CNS drug delivery enhancement

Elacridar (investigational) — CNS drug delivery enhancement

Structural Data:

PDB (33) ✓AlphaFold ✓Cryo-EM ✓

1MVU 6C0V 6QEX 7A65 7A69+28 more

UniProt: F4ZUQ5

Binding Pocket Analysis:

ABCB1 possesses a large, flexible ATP-binding pocket in the nucleotide-binding domains and substrate-binding sites within the transmembrane domain capable of accommodating structurally diverse substrates; crystal structures reveal multiple allosteric modulation sites distinct from the ATP pocket, offering opportunities for selective inhibitor design that avoids disrupting ATP hydrolysis-coupled transport.

🧬 3D Protein Structure

🧬 ABCB1 — PDB 6C0V Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

ABCB1 inhibition carries significant selectivity challenges due to its broad substrate specificity and overlapping substrate recognition with other ABC transporters (ABCC, ABCG2), risking off-target CNS toxicity from accumulation of endogenous or co-administered substrates. Selectivity advantages exist in targeting allosteric modulation sites distinct from the main ATP-binding pocket, potentially offering more selective CNS-penetration enhancement.