TET2

Tet methylcytosine dioxygenase 2

Score: 0.611 Price: $0.61 Low Druggability Status: active Wiki: TET2

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

279

DEBATES

3D Protein Structure

🧬 TET2 — PDB 4NM6 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.42

Clinical Stage

Phase II

Target Class

Epigenetic Regulator

Safety

0.60

Druggability Analysis

Drug Development0.30

Structural Tractability0.70

Target Class0.70

Safety Profile0.60

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (2 compounds)

Therapeutic Areas:

Neurodegenerative diseases (Alzheimer's disease, cognitive decline) Hematologic malignancies (TET2 loss-of-function cancers) Myelodysplastic syndromes Age-related neuroinflammation Epigenetic therapy

Druggability Rationale: TET2 demonstrates moderate druggability (0.55) supported by multiple high-resolution crystal structures (best resolution 1.8Å) and existing proof-of-concept with Vitamin C cofactor enhancement and Bobcat339 preclinical data. The target's classification as an epigenetic regulator with a defined catalytic mechanism and accessible binding sites increases tractability, though the reliance on cofactor (α-ketoglutarate, Fe2+) supplementation suggests modulators may face challenges in achieving drug-like selectivity over other 2-oxoglutarate-dependent dioxygenases.

Mechanism: Small molecule enhancers of TET2 enzymatic activity or cofactor supplementation

Drug Pipeline (2 compounds)

Known Drugs:

Vitamin C (Approved) — Cofactor enhancement

Bobcat339 (Preclinical) — Cancer

Structural Data:

PDB (6) ✓AlphaFold ✓Cryo-EM —

4NM6 5D9Y 5DEU 7NE3 7NE6+1 more

UniProt: A7E237

Binding Pocket Analysis:

TET2 contains a well-characterized catalytic pocket housing iron coordination sites and α-ketoglutarate binding regions, evidenced by 6 PDB structures with resolution down to 1.8Å. Allosteric modulation sites may exist beyond the active site, offering opportunities for selective TET2 enhancement without direct catalytic site competition.

🧬 3D Protein Structure

🧬 TET2 — PDB 4NM6 Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

TET2 selectivity must be carefully optimized against other TET family members (TET1, TET3) and related α-ketoglutarate-dependent dioxygenases (PHD, FIH) to minimize off-target effects. Isoform selectivity is achievable through targeting TET2-specific structural features given distinct cofactor binding pockets among TET proteins.