SLC16A1

Monocarboxylate transporter 1 (MCT1)

Score: 0.590 Price: $0.50 Low Druggability Status: active Wiki: SLC16A1

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🧬 SLC16A1 — PDB 7BP3 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.38

Clinical Stage

Phase II

Target Class

Transporter

Safety

0.55

Druggability Analysis

Drug Development0.30

Structural Tractability0.70

Target Class0.70

Safety Profile0.55

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (3 compounds)

Therapeutic Areas:

Neurodegenerative diseases (Parkinson's, Alzheimer's) Epilepsy Stroke/ischemic brain injury Traumatic brain injury (TBI) Multiple sclerosis Metabolic encephalopathies Oncology (as secondary indication)

Druggability Rationale: MCT1 is tractable for small-molecule modulation (druggability score 0.60) due to its well-characterized transmembrane topology and proof-of-concept from existing inhibitors like AZD3965 in clinical trials. However, the transporter class presents challenges in achieving selective modulation without disrupting essential metabolic functions, and the therapeutic strategy requires fine-tuned restoration of MCT1/MCT4 balance rather than simple inhibition.

Mechanism: Transporter modulation — restoring MCT1/MCT4 balance to normalize astrocyte-neuron metabolic coupling

Drug Pipeline (3 compounds)

Known Drugs:

AZD3965 (Phase I/II (oncology))

AR-C155858 (Preclinical)

BAY-8002 (Preclinical)

Structural Data:

PDB (5) ✓AlphaFold ✓Cryo-EM ✓

6LZ0 7BP3 7CKO

UniProt: P53985

Binding Pocket Analysis:

MCT1 lacks a well-defined orthosteric binding pocket typical of GPCRs or kinases; inhibitors are thought to bind to an intracellular substrate-access pocket near the transporter's central cavity. Structure-activity relationships remain limited due to sparse high-resolution cryo-EM or X-ray structural data, necessitating structure-based drug design efforts using homology models or emerging cryo-EM structures of MCT family members.

🧬 3D Protein Structure

🧬 SLC16A1 — PDB 7BP3 Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selective MCT1 inhibition must avoid off-target effects on MCT2, MCT3, and MCT4 to prevent disrupting the astrocyte-neuron lactate shuttle; peripheral MCT1 expression in red blood cells, intestine, and skeletal muscle presents additional selectivity challenges and potential toxicity risks that require brain-penetrant, CNS-selective chemical scaffolds.