Druggability & Clinical Context
Druggability
Low
Score: 0.42
Target Class
Epigenetic Regulator
Druggability Analysis
Structural Tractability0.70
Key Metrics
PDB Structures:
6
Known Drugs:
2
Approved:
0
In Clinical Trials:
0
Drug Pipeline (2 compounds)
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 —
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.
Clinical Trials (6)
Relevant trials from ClinicalTrials.gov
By Phase
EARLY_PHASE1: 1 · NA: 1 · PHASE1: 1 · PHASE2: 2 · Unknown: 1
NA
NCT06790771
n=25
Hunger
Interventions: High Dose Supplement, Low Dose Supplement, Placebo
Sponsor: Texas Christian University | Started: 2025-01-15
PHASE1
NCT02606773
n=32
Vitamin C Deficiency
Interventions: Ascorbic Acid
Sponsor: Semmelweis University | Started: 2015-06
PHASE2
NCT01897792
n=11
Coagulopathy, Nosocomial Pneumonia
Interventions: Vitamin C, Vitamin E, Saline (for Vitamin C)
Sponsor: University of Alabama at Birmingham | Started: 2013-05
PHASE2
NCT02369822
n=60
Idiopathic Epilepsy
Interventions: Vitamin C
Sponsor: Ain Shams University | Started: 2015-02
EARLY_PHASE1
NCT02424201
n=660
Primary Postpartum Haemorrhage
Interventions: Misoprostol, vitamin c
Sponsor: Lagos State University | Started: 2015-06
Unknown
NCT02635451
n=40
Preterm Premature Rupture of Membranes
Sponsor: Ain Shams Maternity Hospital | Started: 2016-01