SLC16A2

Monocarboxylate transporter 8

Score: 0.427 Price: $0.43 Low Druggability Status: active Wiki: SLC16A2

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🧬 SLC16A2 — PDB 4QSP Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.39

Clinical Stage

Phase I

Target Class

Transporter

Safety

0.70

Druggability Analysis

Drug Development0.15

Structural Tractability0.70

Target Class0.70

Safety Profile0.70

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (1 compounds)

1 Preclinical

Therapeutic Areas:

Rare genetic neurological disorders (Allan-Herndon-Dudley syndrome) X-linked intellectual disability Thyroid hormone metabolism disorders Neurodegeneration with metabolic dysfunction Pediatric neurological disease

Druggability Rationale: SLC16A2 presents a challenging druggability profile (0.30 score) due to its transporter nature and inherent structural constraints in targeting substrate-binding pockets on membrane proteins. However, the existence of investigational thyroid hormone analogs (triiodothyroacetic acid) and multiple high-resolution crystal structures (best resolution 3.0 Å) demonstrate feasibility for substrate supplementation approaches, though allosteric modulation remains underdeveloped.

Mechanism: Substrate supplementation or transporter modulation

Drug Pipeline (1 compounds)

1 Preclinical

Known Drugs:

Triiodothyroacetic acid (investigational) — MCT8 deficiency

Structural Data:

PDB (7) ✓AlphaFold ✓Cryo-EM ✓

8ZKN 8ZKO 9DWY 9FKN 9FOT+2 more

UniProt: K7ELT4

Binding Pocket Analysis:

MCT8 contains a substrate-binding pocket optimized for thyroid hormones (T3, T4) characterized by aromatic residue interactions and a hydrophobic core, as revealed by cryo-EM and crystal structures (PDB: 8ZKN, 9DWY). The transporter likely employs an alternating access mechanism with distinct inward- and outward-facing conformations, providing opportunities for state-selective modulators to enhance or bypass defective transport.

🧬 3D Protein Structure

🧬 SLC16A2 — PDB 4QSP Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selectivity is a major challenge given MCT8's tissue-specific expression in brain and peripheral tissues; off-target transport of substrates to other SLC16 family members (MCT1, MCT4, MCT10) could cause systemic effects. Conversely, the restricted CNS penetration requirement and X-linked inheritance pattern offer a natural selectivity advantage for brain-targeted thyroid hormone analogs over systemic monocarboxylate transporters.

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 (1)

Relevant trials from ClinicalTrials.gov

Active

Completed

Total Enrollment

By Phase

PHASE1: 1

Study With a Topical Gel Containing TRIAC and DHEA in Subjects With Skin Atrophy Due to Glucocorticoids Unknown

PHASE1 NCT03783988 n=10

Skin Atrophy

Interventions: DHEA and TRIAC

Sponsor: Trophea Development AB | Started: 2019-01-15

Linked Hypotheses (1)

Astrocytic Lactate Shuttle Enhancement for Grid Cell Bioenergetics0.412

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

Debate History (0)

No debates yet

SLC16A2

3D Protein Structure

Druggability & Clinical Context

🧬 3D Protein Structure

Selectivity & Safety Considerations

3D Protein Structure

Clinical Trials (1)

Linked Hypotheses (1)

Linked Experiments (0)

Scoring Dimensions

Knowledge Graph (20)

associated with (4)

causes (1)

co discussed (5)

contributes to (1)

expressed in (1)

implicated in (2)

participates in (1)

regulates (2)

therapeutic target (2)

transports (1)

Debate History (0)