DNMT1

DNA methyltransferase 1

Score: 0.567 Price: $0.57 Medium Druggability Status: active Wiki: DNMT1

🧠 Neurodegeneration

HYPOTHESES

6

PAPERS

36

KG EDGES

191

DEBATES

1

3D Protein Structure

🧬 DNMT1 — PDB 3PTA Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.52

Clinical Stage

Approved

Target Class

Epigenetic Regulator

Safety

0.30

Druggability Analysis

Drug Development0.90

Structural Tractability0.85

Target Class0.70

Safety Profile0.30

Key Metrics

PDB Structures:

38

Known Drugs:

2

Approved:

2

In Clinical Trials:

0

Drug Pipeline (2 compounds)

2 Approved

Druggability Rationale: DNMT1 is highly druggable with a 0.90 score, supported by 38 PDB structures at excellent resolution (1.79 Å), two FDA-approved inhibitors (5-azacytidine and decitabine), and established chemical matter targeting its catalytic domain. The abundance of structural data and clinical validation through Phase 4 trials demonstrates feasibility for rational drug design and optimization of selectivity.

Mechanism: Small molecule inhibitor of DNA methyltransferase activity

Drug Pipeline (2 compounds)

2 Approved

Known Drugs:

5-azacytidine (approved) — myelodysplastic syndromes

decitabine (approved) — myelodysplastic syndromes

Structural Data:

PDB (38) ✓AlphaFold ✓Cryo-EM ✓

3AV4 3AV5 3AV6 3EPZ 3PT6+33 more

UniProt: A0A7I2YQA8

🧬 3D Protein Structure

🧬 DNMT1 — PDB 3PTA Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

DNMT1 selectivity remains challenging due to high sequence homology with other DNMT isoforms (DNMT3A/3B), risking off-target methyltransferase inhibition and potential toxicity. Achieving isoform-selective inhibition requires targeting DNMT1-specific regulatory regions or exploiting unique structural features in the UHRF1 binding interface rather than the conserved catalytic domain.

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

3

Completed

4

Total Enrollment

624

By Phase

PHASE1: 2 · PHASE2: 6

Prolonged Ultra Low-dose Decitabine Plus Venetoclax for Primary Diagnosed Elderly AMLK/MDS Recruiting

PHASE2 NCT06046313 n=120

Acute Myeloid Leukemia, Myelodysplastic Syndromes

Interventions: Decitabine for Injection, VENCLYXTO

Sponsor: First Affiliated Hospital of Zhejiang University | Started: 2023-10-19

Combination Salvage Therapy With Venetoclax and Decitabine in Relapsed/Refractory AML Recruiting

PHASE2 NCT06156579 n=27

AML, MDS

Interventions: Decitabine, Venetoclax

Sponsor: University Hospital Tuebingen | Started: 2023-11-04

Pharmacokinetics, Safety, and Efficacy of ASTX727 in Combination With Venetoclax in Acute Myeloid Leukemia (AML) Active Not Recruiting

PHASE1 NCT04657081 n=101

Acute Myeloid Leukemia

Interventions: Decitabine and Cedazuridine (ASTX727), Venetoclax

Sponsor: Taiho Oncology, Inc. | Started: 2021-02-09

5-azacytidine Valproic Acid and ATRA in AML and High Risk MDS Completed

PHASE2 NCT00339196 n=25

Acute Myelogenous Leukaemia (AML), Myelodysplastic Syndrome (MDS)

Interventions: 5 azacytidine - VALPROIC acid- Retinoic

Sponsor: Assistance Publique - Hôpitaux de Paris | Started: 2006-07

Multicenter Study to Assess the Efficacy of Decitabine in the Treatment of Chronic Myelomonocytic Leukemia Completed

PHASE2 NCT01251627 n=43

Chronic Myelomonocytic Leukemia

Interventions: Decitabine

Sponsor: Fondazione Italiana Sindromi Mielodisplastiche-ETS | Started: 2010-04

PhII 5-Azacytidine Plus Valproic Acid and Eventually Atra in Intermediate II and High Risk MDS Completed

PHASE2 NCT00439673 n=62

Myelodysplastic Syndromes

Interventions: 5-Azacytidine, Valproic Acid, ATRA

Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto | Started: 2007-05

Study of Low-Dose Intravenous Decitabine in Patients Aged > 60 Years With Acute Myeloid Leukemia Completed

PHASE2 NCT00866073 n=238

Acute Myeloid Leukemia

Interventions: Decitabine 15 mg/m2 i.v.

Sponsor: University Hospital Freiburg | Started: 2003-04

A Study Of PF-06747143, As Single Agent Or In Combination With Standard Chemotherapy In Adult Patients With Acute Myeloi Terminated

PHASE1 NCT02954653 n=8

Acute Myeloid Leukemia

Interventions: PF-06747143, Cytarabine, Daunorubicin

Sponsor: Pfizer | Started: 2016-11-28

Linked Hypotheses (2)

DNMT1-Targeting Antisense Oligonucleotide Reset0.648

DNMT1 Compensation Window During Synaptic Resilience Phase0.528

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (11)

DNMT1→neurodegenerationACTB→DNMT1GABARAP→DNMT1ULK1→DNMT1WIPI2→DNMT1

▸ Show 6 more

LC3→DNMT1BECN1→DNMT1HTT→DNMT1ATG7→DNMT1SETX→DNMT1SQSTM1→DNMT1

co discussed (5)

HDAC3→DNMT1TET2→DNMT1KDM6A→DNMT1SIRT6→DNMT1DNMT1→FOXO3

interacts with (4)

SNCA→DNMT1HSPA1A→DNMT1DNMT1→SNCADNMT1→HSPA1A

Debate History (1)

Should DNMT1 (DNA methyltransferase 1) be prioritized as a therapeutic target fo2026-04-21