OncoSignal
Live from Open Targets Platform, fetched 2026-11-12 01:05 UTC. Every row links to its source record.

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}.

In 11 of 15 cancers, the evidence for ALDH2 comes mainly from mutations found in tumours

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.

Inherited (germline) variantsMutations in tumours (somatic)
00.250.50.751colorectal cancercolorectal cancercolorectal cancer: germline 0.66carcinoma of esophaguscarcinoma of esophaguscarcinoma of esophagus: somatic 0.15carcinoma of esophagus: germline 0.51head and neck squamous cell carcinomahead and neck squamous cell carcinomahead and neck squamous cell carcinoma: somatic 0.30head and neck squamous cell carcinoma: germline 0.38glioblastomaglioblastomamelanomamelanomamelanoma: somatic 0.30non-small cell lung carcinomanon-small cell lung carcinomanon-small cell lung carcinoma: somatic 0.15hepatocellular carcinomahepatocellular carcinomahepatocellular carcinoma: somatic 0.30lung adenocarcinomalung adenocarcinomalung adenocarcinoma: somatic 0.30acute myeloid leukemiaacute myeloid leukemiaacute myeloid leukemia: somatic 0.30lung carcinomalung carcinomalung carcinoma: somatic 0.30esophageal squamous cell carcinomaesophageal squamous cell carcinomaesophageal squamous cell carcinoma: somatic 0.30breast carcinomabreast carcinomabreast carcinoma: somatic 0.30oral cavity squamous cell carcinomaoral cavity squamous cell carcinomaoral cavity squamous cell carcinoma: somatic 0.30bladder transitional cell carcinomabladder transitional cell carcinomabladder transitional cell carcinoma: somatic 0.30gastric carcinomagastric carcinomagastric carcinoma: somatic 0.30

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.

14 of 18 trials of drugs against ALDH2 have sites only in United States

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.

Sites only in this groupSites here and elsewhere
United StatesUnited States: 14 trials with sites only hereUnited States: 0 trials with sites here and elsewhere14EuropeEurope: 2 trials with sites only hereEurope: 0 trials with sites here and elsewhere2OtherOther: 2 trials with sites only hereOther: 0 trials with sites here and elsewhere2

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.

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.

DrugTypeHighest stageIndicationsSource records
DISULFIRAMSmall moleculephase 4alcohol dependence, parasitic infectious disease, non-small cell lung carcinoma, glioblastoma, cocaine dependence, opiate dependence, cocaine abuse, melanoma, +22 moreOpen Targets · ChEMBL