ALDH2 aldehyde dehydrogenase 2 family member
ENSG00000111275 · protein coding · Open Targets profile
Mitochondrial aldehyde dehydrogenase with broad substrate specificity which participates in the detoxification of ethanol-derived acetaldehyde and endogenous aldehydes, including those arising from lipid peroxidation (PubMed:16956664, PubMed:22339434, PubMed:33355142, PubMed:39075523). The reaction mechanism involves a nucleophilic attack on the aldehyde substrate, resulting in formation of a thiohemiacetal intermediate. Subsequent hydride transfer to NAD+, yields a thioester intermediate which is hydrolyzed to the carboxylic acid product through activation of a water molecule by the catalytic glutamate (PubMed:19506075). In vivo, ALDH2 is required for the clearance of formaldehyde, a cytotoxic and carcinogenic endogenous metabolite that induces DNA damage (PubMed:33355142). It also catalyzes the oxidation of 3,4-dihydroxyphenylacetaldehyde (DOPAL), a reactive intermediate of dopamine catabolism, to 3,4-dihydroxyphenylacetate (DOPAC) (PubMed:16956664). ALDH2 may also catalyze the oxidation of 4- aminobutanal (gamma-aminobutyraldehyde) to 4-aminobutanoate (GABA), representing an alternative route for GABA biosynthesis from polyamine catabolism (By similarity). In vitro, ALDH2 catalyzes the oxidation of acrolein, malondialdehyde, and 4-hydroxynonenal (4-HNE) (PubMed:22339434). It also exhibits esterase activity that is enhanced by NAD+ but does not require it, although the physiological relevance of this activity remains unclear (PubMed:19506075). {ECO:0000250|UniProtKB:P20000, ECO:0000269|PubMed:16956664, ECO:0000269|PubMed:19506075, ECO:0000269|PubMed:22339434, ECO:0000269|PubMed:33355142, ECO:0000269|PubMed:39075523}.
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, High-Quality Pocket, Druggable Family
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.7383900284767151 (upper bound 0.9493799805641174). 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 19 registry trials, updated in the last three years, of the most advanced drugs against ALDH2 (disulfiram), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Asadullah KhanWake Forest University Health Sciences · 1 of 1 trials Phase 2+
- Beatriz Y HanaokaUniversity of Oklahoma · 1 of 1 trials Phase 2+
- Brian A FallonColumbia University · 1 of 1 trials Phase 2+
- Damon ReedMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Debarshi MustafiUniversity of Washington · 1 of 1 trials Phase 2+
- Jiayi HuangWashington University School of Medicine · 1 of 1 trials Phase 2+
- Marian HajduchPalacky University · 1 of 1 trials Phase 2+
- Petros N KaramanakosDepartment of Neurosurgery, Olympion Medical Center, 26443, Patras, GREECE · 1 of 1 trials Phase 2+
- Sharon R LewinThe Doherty Institute, University of Melbourne · 1 of 1 trials Phase 2+
- Steven LinUT MD Anderson · 1 of 1 trials Phase 2+
- Thuraiya Al HarthiOman MoH · 1 of 1 trials Phase 2+
- Aminah JatoiMayo Clinic in Rochester · 0 of 1 trials Phase 2+
- Eric J. HawkinsVA Puget Sound Health Care System Seattle Division, Seattle, WA · 0 of 1 trials Phase 2+
- Matteo TruccoCleveland Clinic, Case Comprehensive Cancer Center · 0 of 1 trials Phase 2+
- Tiffany HodgesUniversity Hospitals Cleveland Medical Center · 0 of 1 trials Phase 2+
Registry trials of disulfiram 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; 18 of 18 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. 1 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
11 trials of drugs against ALDH2 were stopped early
Terminated, withdrawn and suspended interventional trials of disulfiram, 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 11 most recent of 11.
- terminated · 2025-01-07 · Mayo Clinic · Disulfiram“lack of funding”
- terminated · 2024-10-03 · Wake Forest University Health Sciences · Disulfiram“Investigator decision”
- terminated · 2024-02-09 · University of Melbourne · Disulfiram, (National Drug Code) NDC 0378-4141-01“A re-evaluation of research risks to participants were greater than originally anticipated”
- terminated · 2023-10-18 · HonorHealth Research Institute · nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper Gluconate, FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate, Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate“Study was closed due to low subject enrollment at site.”
- withdrawn · 2023-10-06 · National Cancer Institute, Slovakia · Disulfiram“Poor acrual”
- terminated · 2023-09-13 · University of California, San Francisco · Disulfiram“Low COVID case numbers, competing COVID treatments available”
- terminated · 2023-03-13 · University of Utah · Disulfiram“Closed at PI's Request”
- terminated · 2021-09-16 · Daniel George, MD · Disulfiram“Study stopped due to lack of efficacy.”
- terminated · 2020-09-28 · Sahlgrenska University Hospital · Disulfiram“Problems with including patients”
- terminated · 2019-08-07 · University of California, Irvine · Disulfiram“Halted because of slow accrual and lack of study funding”
- withdrawn · 2014-12-09 · Assistance Publique - Hôpitaux de Paris · Disulfiram“Too selective recrutment criteria, none eligible patients”
Paediatric incentives and obligations for ALDH2's drugs
For disulfiram: 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 · ALDH2 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: no · No EMA paediatric investigation plan decision names disulfiramRule: 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: no · No EU orphan designation names disulfiramRule: 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: no · EMA lists no centrally authorised medicine of disulfiramRule: 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 disulfiramRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 1 interventional studies of disulfiram include patients under 18; 1 is 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, 2026-11-12
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 1 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.
| Drug | Type | Highest stage | Indications | Source records |
|---|---|---|---|---|
| DISULFIRAM | Small molecule | phase 4 | alcohol dependence, parasitic infectious disease, non-small cell lung carcinoma, glioblastoma, cocaine dependence, opiate dependence, cocaine abuse, melanoma, +22 more | Open Targets · ChEMBL |