DNMT3A DNA methyltransferase 3 alpha
ENSG00000119772 · protein coding · Open Targets profile
Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development (PubMed:12138111, PubMed:16357870, PubMed:30478443). DNA methylation is coordinated with methylation of histones (PubMed:12138111, PubMed:16357870, PubMed:30478443). It modifies DNA in a non-processive manner and also methylates non-CpG sites (PubMed:12138111, PubMed:16357870, PubMed:30478443). May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1 (By similarity). Plays a role in paternal and maternal imprinting (By similarity). Required for methylation of most imprinted loci in germ cells (By similarity). Acts as a transcriptional corepressor for ZBTB18 (By similarity). Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites (By similarity). Can actively repress transcription through the recruitment of HDAC activity (By similarity). Also has weak auto-methylation activity on Cys-710 in absence of DNA (By similarity). {ECO:0000250|UniProtKB:O88508, ECO:0000269|PubMed:12138111, ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:30478443}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Druggable Family
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 2.270400047302246 (upper bound 2.5125999450683594). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 255 registry trials, updated in the last three years, of the most advanced drugs against DNMT3A (decitabine), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Farhad Ravandi-KashaniM.D. Anderson Cancer Center · 3 of 3 trials Phase 2+Ph2NCT04746235 · Venetoclax and ASTX727 for the Treatment of Relapsed, Refractory, or Newly Diagnosed Acute Myeloid Leukemiabrief
- Nicholas ShortM.D. Anderson Cancer Center · 2 of 3 trials Phase 2+Ph1NCT06401603 · A Phase I Study of Decitabine, Lisaftoclax, and Olverembatinib in Patients With Advanced Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Myeloid Leukemiabrief
- Abhishek MaitiM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- Anand A PatelAlliance for Clinical Trials in Oncology · 2 of 2 trials Phase 2+
- Anna HalpernFred Hutch/University of Washington Cancer Consortium · 2 of 2 trials Phase 2+
- Courtney DiNardoM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- Guillermo Garcia-ManeroM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- Jianxiang WangInstitute of Hematology & Blood Diseases Hospital, China · 2 of 2 trials Phase 2+
- Najla El JurdiNational Cancer Institute (NCI) · 2 of 2 trials Phase 2+
- Tapan KadiaM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- Bing XuThe First Aiffiliated hosptical of xiamen University · 1 of 2 trials Phase 2+
- Mendel GoldfingerMontefiore/Einstein Cancer Center · 1 of 2 trials Phase 2+
- Alice MimsBeat AML · 1 of 1 trials Phase 2+
- Amanda CashenWashington University School of Medicine · 1 of 1 trials Phase 2+
- Andrej LissatCharité · 1 of 1 trials Phase 2+
Registry trials of decitabine updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 206 of 242 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 13 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
103 trials of drugs against DNMT3A were stopped early; 10 give no reason
Terminated, withdrawn and suspended interventional trials of decitabine, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 103.
- suspended · 2026-10-20 · City of Hope Medical Center · Decitabine“Accrual goal Met”
- terminated · 2026-10-08 · Taiho Oncology, Inc. · Decitabine + Cedazuridine“ASTX660-03 was closed according to protocol as no safe and tolerable dosing for the combination of tolinapant and decitabine/cedazuridine was identified based on protocol defined criteria.”
- suspended · 2026-08-24 · National Cancer Institute (NCI) · Decitabine and Cedazuridine“Drug Supply Issues”
- suspended · 2026-07-31 · National Cancer Institute (NCI) · Decitabine and Cedazuridine“Other - DLT assessment and phase 2 dose determination”
- withdrawn · 2026-06-22 · Case Comprehensive Cancer Center · Decitabine“PI leaving the institution”
- terminated · 2026-06-08 · University of Southern California · Decitabine“Lack of funding”
- withdrawn · 2026-05-15 · M.D. Anderson Cancer Center · matched by the registry's drug synonyms“Abandoned”
- suspended · 2026-04-23 · Sclnow Biotechnology Co., Ltd. · Decitabine“Others”
- terminated · 2026-03-10 · M.D. Anderson Cancer Center · Decitabine“<75% participation”
- withdrawn · 2026-02-13 · M.D. Anderson Cancer Center · matched by the registry's drug synonyms“Drug Source Request”
- terminated · 2026-02-11 · Institute of Hematology & Blood Diseases Hospital, China · Decitabine“Not achieve the desired effect”
- terminated · 2026-01-22 · Delta-Fly Pharma, Inc. · Decitabine“The data met the protocol-specified criteria for futility of the investigational treatment.”
- terminated · 2026-01-13 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“In December 2023, Novartis decided to terminate the sabatolimab clinical development program early after Phase II (MDS1) and Phase III (MDS2) studies failed to meet their primary objectives. The termination was not due to safety concerns.”
- terminated · 2026-01-09 · Sanjay Mohan · Decitabine“Study was terminated early due to lack of accrual and loss of funding.”
- terminated · 2025-12-02 · National Cancer Institute (NCI) · matched by the registry's drug synonyms“Drug company withdrew support.”
- terminated · 2025-11-12 · Roswell Park Cancer Institute · Decitabine and Cedazuridine“PI closed study”
- terminated · 2025-10-16 · Novartis Pharmaceuticals · Decitabine, INQOVI (oral decitabine)“Lack of efficacy in the program as demonstrated in the earlier CMBG453B12301 (STIMULUS MDS-2) study.”
- terminated · 2025-09-30 · National Cancer Institute (NCI) · Deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) Decitabine“Company closed the trial.”
- suspended · 2025-08-29 · Johns Hopkins University · Decitabine“IRB00247544 is lapsed. Separate application submitted for reactivation under IRB00521868. Awaiting review \& approval”
- withdrawn · 2025-08-06 · M.D. Anderson Cancer Center · Decitabine“0 participants”
- withdrawn · 2025-05-30 · Institute of Hematology & Blood Diseases Hospital, China · Decitabine“No participants enrolled”
- withdrawn · 2025-05-25 · City of Hope Medical Center · Decitabine“cprmc withdrawn”
- terminated · 2025-04-24 · Seoul National University Hospital · Decitabine with GemOx“slow recruitment”
- withdrawn · 2025-04-22 · University of Florida · Decitabine, azacitidine or decitabine“Study disapproved by internal scientific review committee on re-review; study will no longer move forward”
- withdrawn · 2025-03-24 · Columbia University · DecitabineCedazuridine (Inqovi ®)“Difficultly enrolling”
Paediatric incentives and obligations for DNMT3A's drugs
For decitabine: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · DNMT3A is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMA/PE/0000246985 (cedazuridine;decitabine, Treatment of acute myeloid leukaemia): PM: decision on the application for modification of an agreed PIP, 26 Jun 2025; EMEA-003071-PIP02-23 (cedazuridine;decitabine, Treatment of myelodysplastic syndromes, including juvenile myelomonocytic leukaemia): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 21 Dec 2023; EMEA-003404-PIP01-23 (decitabine;tetrahydrouridine, Treatment of sickle cell disease): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 1 Dec 2023; EMEA-000555-PIP01-09-M06 (decitabine, Treatment of acute myeloid leukaemia): PM: decision on the application for modification of an agreed PIP, 9 Aug 2017; compliance positive 18 Oct 2019Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/23/2825 withdrawn 16 Aug 2023: Treatment of myelodysplastic syndromes; EU/3/21/2548 withdrawn 10 Dec 2021: Treatment of acute myeloid leukaemia; EU/3/20/2338 positive 19 Oct 2020: Treatment of sickle cell disease; EU/3/17/1881 positive 20 Jun 2017: Treatment of sickle cell disease; +2 moreRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Inaqovi: authorised since 15 Sept 2023; Dacogen: authorised since 20 Sept 2012Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of decitabineRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 99 interventional studies of decitabine include patients under 18; 24 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 2 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.