ABCB1

P-glycoprotein

Score: 0.520 Price: $0.52 Medium Druggability Status: active Wiki: ABCB1

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

17

KG EDGES

373

DEBATES

1

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:

33

Known Drugs:

2

Approved:

0

In Clinical Trials:

0

Drug Pipeline (2 compounds)

2 Preclinical

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

🧬 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.

3D Protein Structure

PDB: Open in RCSB AlphaFold model

Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.

Clinical Trials (8)

Relevant trials from ClinicalTrials.gov

Active

0

Completed

7

Total Enrollment

1,243

By Phase

PHASE1: 2 · PHASE2: 4 · PHASE3: 1 · Unknown: 1

Surgery Plus Chemotherapy (Doxorubicin, Vincristine and Etoposide), Mitotane, and Tariquidar to Treat Adrenocortical Can Completed

PHASE2 NCT00071058 n=50

Adrenal Cortex Neoplasms

Interventions: XR9576 (Tariquidar)

Sponsor: National Cancer Institute (NCI) | Started: 2003-10

PET Imaging With Tc-94m Sestamibi to Assess Resistance to Chemotherapy Completed

PHASE2 NCT00082368 n=12

Cancer

Interventions: Tariquidar, Tc-94m Sestamibi

Sponsor: National Cancer Institute (NCI) | Started: 2004-05-16

Phase II Study to Evaluate Tariquidar (XR9576), a Selective MDR-1 Inhibitor, in Chemotherapy Resistant Advanced Breast C Completed

PHASE2 NCT00048633 n=30

Breast Neoplasms

Interventions: Chemotherapy

Sponsor: QLT Inc. | Started: 2001-11

Tariquidar and Docetaxel to Treat Patients With Lung, Ovarian, Renal and Cervical Cancer Completed

PHASE2 NCT00069160 n=48

Lung Neoplasms, Ovarian Neoplasms, Cervix Neoplasms

Interventions: docetaxel, tariquidar, 99mTc-sestamibi imaging

Sponsor: National Cancer Institute (NCI) | Started: 2003-09

Phase I Trial of Tariquidar (XR9576) in Combination With Doxorubicin, Vinorelbine, or Docetaxel in Pediatric Patients Wi Completed

PHASE1 NCT00011414 n=29

Wilms' Tumor, Sarcoma, Adenaocortical Carcinoma

Interventions: Tariquidar

Sponsor: National Cancer Institute (NCI) | Started: 2001-02-15

Tariquidar-ondansetron Combination in Neuropathic Pain Completed

PHASE1 NCT04603066 n=24

Neuropathic Pain

Interventions: Ondansetron 16 mg with Tariquidar, Ondansetron 16 mg with Placebo

Sponsor: Washington University School of Medicine | Started: 2021-01-31

CLarifying ABCB1's Role in Alzheimer's Disease Completed

Unknown NCT07393113 n=510

Alzheimer Disease

Interventions: ABCB1 genotyping

Sponsor: Assistance Publique - Hôpitaux de Paris | Started: 2023-10-25

A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Phase III Study of Tariquidar + Paclitaxel/Carboplatin as F Terminated

PHASE3 NCT00042302 n=540

Stage IIIb Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Interventions: Chemotherapy, tariquidar + paclitaxel/carboplatin, placebo + paclitaxel/carboplatin

Sponsor: QLT Inc. | Started: 2002-06

Linked Hypotheses (0)

No linked hypotheses

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (2)

ABCB1→neurodegenerationMAOB→ABCB1

co discussed (11)

LRP1→ABCB1LDLR→ABCB1TFR1→ABCB1AQP4→ABCB1CAV1→ABCB1

▸ Show 6 more

ABCB1→FCGRTOCLN→ABCB1APOE→ABCB1MTNR1A→ABCB1MTNR1B→ABCB1ABCB1→CLDN5

contributes to (1)

interacts with (6)

TFR1→ABCB1LRP1→ABCB1CAV1→ABCB1ABCB1→TFR1ABCB1→LRP1

▸ Show 1 more

Debate History (1)

Should ABCB1 (P-glycoprotein) be prioritized as a therapeutic target for neurode2026-04-22