ALDH2
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Summary
ALDH2 (aldehyde dehydrogenase 2 family member, HGNC:404) is a protein-coding gene on chromosome 12q24.12, encoding Aldehyde dehydrogenase, mitochondrial (P05091). Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage.
This protein belongs to the aldehyde dehydrogenase family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. Two major liver isoforms of aldehyde dehydrogenase, cytosolic and mitochondrial, can be distinguished by their electrophoretic mobilities, kinetic properties, and subcellular localizations. Most Caucasians have two major isozymes, while approximately 50% of East Asians have the cytosolic isozyme but not the mitochondrial isozyme. A remarkably higher frequency of acute alcohol intoxication among East Asians than among Caucasians could be related to the absence of a catalytically active form of the mitochondrial isozyme. The increased exposure to acetaldehyde in individuals with the catalytically inactive form may also confer greater susceptibility to many types of cancer. This gene encodes a mitochondrial isoform, which has a low Km for acetaldehydes, and is localized in mitochondrial matrix. Alternative splicing results in multiple transcript variants encoding distinct isoforms.
Source: NCBI Gene 217 — RefSeq curated summary.
At a glance
- GWAS associations: 93
- Clinical variants (ClinVar): 56 total
- Phenotypes (HPO): 3
- Druggable target: yes — 3 molecules with ChEMBL bioactivity
- Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
- MANE Select transcript:
NM_000690
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:404 |
| Approved symbol | ALDH2 |
| Name | aldehyde dehydrogenase 2 family member |
| Location | 12q24.12 |
| Locus type | gene with protein product |
| Status | Approved |
| Ensembl gene | ENSG00000111275 |
| Ensembl biotype | protein_coding |
| Entrez | 217 |
Gene structure
Transcript identifiers
Ensembl transcripts: 42 — 39 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined
ENST00000261733, ENST00000416293, ENST00000548536, ENST00000549106, ENST00000551450, ENST00000871406, ENST00000871407, ENST00000871408, ENST00000871409, ENST00000871410, ENST00000871411, ENST00000871412, ENST00000871413, ENST00000871414, ENST00000871415, ENST00000871416, ENST00000871417, ENST00000871418, ENST00000871419, ENST00000871420, ENST00000871421, ENST00000871422, ENST00000871423, ENST00000871424, ENST00000871425, ENST00000871426, ENST00000871427, ENST00000871428, ENST00000871429, ENST00000871430, ENST00000871431, ENST00000931977, ENST00000931978, ENST00000951568, ENST00000951569, ENST00000951570, ENST00000951571, ENST00000951572, ENST00000951573, ENST00000951574, ENST00000951575, ENST00000951576
RefSeq mRNA: 2 — MANE Select: NM_000690
NM_000690, NM_001204889
CCDS: CCDS55885, CCDS9155
Canonical transcript exons
ENST00000261733 — 13 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001129780 | 111809543 | 111817532 |
| ENSE00002409511 | 111766933 | 111767096 |
| ENSE00003482109 | 111799906 | 111800063 |
| ENSE00003513839 | 111803859 | 111803973 |
| ENSE00003515748 | 111783158 | 111783298 |
| ENSE00003538556 | 111798078 | 111798242 |
| ENSE00003577573 | 111789823 | 111789934 |
| ENSE00003592919 | 111790434 | 111790562 |
| ENSE00003596965 | 111785267 | 111785346 |
| ENSE00003632584 | 111792061 | 111792163 |
| ENSE00003667483 | 111792598 | 111792782 |
| ENSE00003684013 | 111791306 | 111791419 |
| ENSE00003687836 | 111781918 | 111782022 |
Expression profiles
Bgee: expression breadth ubiquitous, 301 present calls, max score 99.59.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 82.4448 / max 3111.2499, expressed in 1611 samples.
FANTOM5 promoters (1 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 128045 | 82.4448 | 1611 |
Top tissues by expression
305 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| right lobe of liver | UBERON:0001114 | 99.59 | gold quality |
| liver | UBERON:0002107 | 99.48 | gold quality |
| lower lobe of lung | UBERON:0008949 | 99.46 | gold quality |
| dorsal motor nucleus of vagus nerve | UBERON:0002870 | 99.37 | gold quality |
| lateral globus pallidus | UBERON:0002476 | 99.33 | gold quality |
| parotid gland | UBERON:0001831 | 99.31 | gold quality |
| CA1 field of hippocampus | UBERON:0003881 | 99.28 | gold quality |
| gingival epithelium | UBERON:0001949 | 99.27 | gold quality |
| medial globus pallidus | UBERON:0002477 | 99.26 | gold quality |
| globus pallidus | UBERON:0001875 | 99.24 | gold quality |
| substantia nigra pars reticulata | UBERON:0001966 | 99.24 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 99.23 | gold quality |
| putamen | UBERON:0001874 | 99.22 | gold quality |
| mucosa of stomach | UBERON:0001199 | 99.20 | gold quality |
| tongue squamous epithelium | UBERON:0006919 | 99.19 | gold quality |
| caudate nucleus | UBERON:0001873 | 99.18 | gold quality |
| middle frontal gyrus | UBERON:0002702 | 99.16 | gold quality |
| right adrenal gland | UBERON:0001233 | 99.15 | gold quality |
| nucleus accumbens | UBERON:0001882 | 99.14 | gold quality |
| cardiac muscle of right atrium | UBERON:0003379 | 99.12 | gold quality |
| amygdala | UBERON:0001876 | 99.10 | gold quality |
| pylorus | UBERON:0001166 | 99.09 | gold quality |
| substantia nigra pars compacta | UBERON:0001965 | 99.07 | gold quality |
| ileal mucosa | UBERON:0000331 | 99.04 | gold quality |
| left adrenal gland | UBERON:0001234 | 99.01 | gold quality |
| adrenal cortex | UBERON:0001235 | 99.01 | gold quality |
| right lung | UBERON:0002167 | 99.01 | gold quality |
| synovial joint | UBERON:0002217 | 99.00 | gold quality |
| substantia nigra | UBERON:0002038 | 98.96 | gold quality |
| body of tongue | UBERON:0011876 | 98.96 | gold quality |
Single-cell (SCXA)
Detected in 11 experiment(s), a significant marker in 10.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-CURD-79 | yes | 1489.86 |
| E-MTAB-8060 | yes | 137.82 |
| E-MTAB-8142 | yes | 81.27 |
| E-CURD-122 | yes | 72.60 |
| E-MTAB-10553 | yes | 30.26 |
| E-GEOD-130148 | yes | 20.06 |
| E-MTAB-9388 | yes | 10.93 |
| E-MTAB-6678 | yes | 8.13 |
| E-MTAB-9801 | yes | 7.06 |
| E-GEOD-83139 | no | 2.74 |
| E-ANND-3 | no | 0.00 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): CEBPB, CEBPG, HES1, HNF4A, MYC, NR2F2, PITX3, PPARA, RARA, TP63
miRNA regulators (miRDB)
31 targeting ALDH2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-6833-3P | 100.00 | 70.63 | 3197 |
| HSA-MIR-4768-5P | 100.00 | 69.49 | 2861 |
| HSA-MIR-30A-5P | 100.00 | 76.31 | 3233 |
| HSA-MIR-30B-5P | 100.00 | 76.29 | 3248 |
| HSA-MIR-30C-5P | 100.00 | 76.29 | 3248 |
| HSA-MIR-30D-5P | 100.00 | 76.32 | 3233 |
| HSA-MIR-30E-5P | 100.00 | 76.32 | 3242 |
| HSA-MIR-4510 | 100.00 | 66.60 | 2050 |
| HSA-MIR-6127 | 100.00 | 66.76 | 2188 |
| HSA-MIR-6129 | 100.00 | 66.46 | 2080 |
| HSA-MIR-6130 | 100.00 | 66.69 | 2012 |
| HSA-MIR-6133 | 100.00 | 66.48 | 2064 |
| HSA-MIR-6758-5P | 100.00 | 66.21 | 1470 |
| HSA-MIR-6856-5P | 100.00 | 65.47 | 1298 |
| HSA-MIR-6809-3P | 99.91 | 71.45 | 3814 |
| HSA-MIR-4753-3P | 99.90 | 71.03 | 3786 |
| HSA-MIR-153-5P | 99.89 | 73.86 | 6317 |
| HSA-MIR-3942-3P | 99.57 | 69.03 | 2854 |
| HSA-MIR-578 | 99.46 | 68.36 | 1787 |
| HSA-MIR-8065 | 99.19 | 70.38 | 1289 |
| HSA-MIR-16-1-3P | 98.70 | 69.23 | 1538 |
| HSA-MIR-3689A-5P | 98.35 | 70.12 | 1049 |
| HSA-MIR-3689B-5P | 98.35 | 70.12 | 1049 |
| HSA-MIR-3689E | 98.35 | 70.12 | 1049 |
| HSA-MIR-3689F | 98.35 | 70.08 | 1052 |
| HSA-MIR-4793-5P | 96.88 | 65.90 | 872 |
| HSA-MIR-4423-5P | 95.24 | 64.42 | 454 |
| HSA-MIR-3679-5P | 94.75 | 66.46 | 862 |
| HSA-MIR-1185-5P | 94.47 | 65.95 | 725 |
| HSA-MIR-4444 | 92.67 | 67.92 | 56 |
Literature-anchored findings (GeneRIF, showing 40)
- a rapid, reliable and inexpensive method, mismatch amplification mutation assay (MAMA), for the determination of human ALDH2 usual and atypical alleles (PMID:11798074)
- Individuals possessing more susceptible ALDH2 1-2/2-2 genotypes were more likely to reveal p53 overexpression. (PMID:12010862)
- The degree of liver dysfunction in alcoholic liver disease with ALDH2*1/2*2 may be less pronounced than that with ALDH2*1/2*1. (PMID:12198368)
- The frequencies of the mutant ALDH2*2 allele were significantly higher in patients with esophageal cancer (27.7%) than in healthy control subjects (7.3%; p< 0.0001; habitual alcohol drinkers). (PMID:12198369)
- ALDH2 Lys/Lys genotype is a risk factor for myocardial infarction in Japanese men due to its influence on HDL cholesterol level. (PMID:12452318)
- No causal relation between hypertension and the ALDH2 genotype per se, after excluding for some confounding factors, especially for alcohol drinking. (PMID:12484509)
- Polymorphisms of alcohol-metabolizing enzymes: analyses of mutations on the CYP2E1, ADH2, ADH3 and ALDH2 genes in a Mexican-American population living in the Los Angeles area. (PMID:12554615)
- Genotype is associated with type 1 diabetes mellitus. (PMID:12706323)
- Maternal inheritance of diabetes is associated with inactive ALDH2 genotype in diabetics with renal failure. (PMID:12706324)
- Alcohol-related red cell value changes associated with inactive ALDH2 in Japanese men suggest the importance of acetaldehyde’s role in increasing MCV and the potential for using MCV as a marker for high-risk drinkers for esophageal cancer. (PMID:14506399)
- genotypes of aldehyde dehydrogenase 2 and beta3-adrenergic receptor were strongly associated with elevated alanine aminotransferase level which increased with the accumulation of components of metabolic syndrome (PMID:14506613)
- The human aldehyde dehydrogenase-2 promoter contains a retinoid response element which may contribute to regulation of the retinoic acid receptor. (PMID:14691372)
- this study of haplotype frequency and linkage disequilibrium of ALDH2 illuminates the global evolutionary history of the ALDH2 gene (PMID:15008789)
- The ALDH2 gene may interact with the dopamine D2 receptor (DRD2) gene in the development of anxiety-depressive alcohol dependence in the Taiwan Han Chinese population. (PMID:15084894)
- ALDH2 gene is implicated in conduct disorders and alcohol dependence in Chinese, Korean and White American individuals (PMID:15122947)
- These results indicate that mitochondrial aldehyde dehydrogenase 2 (ALDH2) functions as a protector against oxidative stress, and that ALDH2 deficiency is a risk factor for late-onset Alzheimer’s disease. (PMID:15126281)
- The accumulation of acetaldehyde due to ALDH2 inactivity is associated with alcoholic polyneuropathy. (PMID:15182962)
- results suggest that ALDH2 catalyses the mitochondrial bioactivation of nitroglycerin by the formation of a reactive NO-related intermediate that activates soluble guanylate cyclase (PMID:15377279)
- Meta-analysis using three diabetes population studies strongly confirmed the association between ALDH2 inactivity and maternal inheritance. (PMID:15563966)
- analyis of aldehyde dehydrogenase 2 tissue distribution and its role in alcohol metabolism (PMID:15569633)
- Smoking habit did increase the risk of pancreatic cancer, and this risk was further enhanced in subjects with inactive ALDH2 in a male population but not in a female population (PMID:15714130)
- ALDH2 genotype is significantly associated with acetaldehyde-induced micronuclei and alcohol-induced facial flushing. (PMID:15840430)
- Polymorphisms of the alcohol metabolism-related ALDH2 gene are significantly different in Korean patients with alcoholism and Korean control subjects without alcoholism. (PMID:15902904)
- x-ray crystallographic structure of ALDH2*2 (PMID:15983043)
- Individuals with the variant alleles ALDH2*2 had a decreased risk of colorectal adenoma, suggesting that folate inhibits the growth of colorectal adenomas. (PMID:16108833)
- None of the 40 subjects with inactive mitochondrial aldehyde dehydrogenase (ALDH2*2 allele) exhibited pancreatitis (P = 0.004). (PMID:16163053)
- Findings indicate that the ALDH2 polymorphism may modify hepatocellular carcinoma risk among light to moderate drinkers. (PMID:16187278)
- interaction between ALDH2 and ADH2 polymorphisms may have a role in colorectal cancer in Japan (PMID:16332725)
- ALDH2*2 allele has been associated with lower rates of alcohol dependence. (PMID:16404797)
- Results suggest that the Lys504 allele of mitochondrial aldehyde dehydrogenase-2 contributes to the lack of an efficacious clinical response to nitroglycerin in Chinese heart disease patients. (PMID:16440063)
- Single Nucleotide Polymorphisms of aldehyde dehydrogenase-2 is associated with esophageal squamous cell carcinoma (PMID:16639733)
- Heterozygous ALDH2 * 1/ * 2 plus homozygous ALDH2 * 2/ * 2 genotype decreased the risk of trichloroethylene-induced medicamentosa-like dermatitis. (PMID:16758956)
- mtALDH overexpression attenuates hyperoxia-induced cell death in lung epithelial cells through reduction of reactive oxygen species, activation of ERK/MAPK, and PI3K-Akt cell survival signaling pathways (PMID:16782756)
- Genetic variation in ALDH2 affects alcohol metabolism in Europeans. However, the data do not support the hypothesis that this leads to effects on alcohol sensitivity, consumption, or risk of dependence. (PMID:16792555)
- possible interaction between the ALDH2 1510 G/A polymorphism and age in head and neck squamous cell carcinoma. (PMID:17033202)
- Results suggest that ALDH2 polymorphisms play a pivotal role on esophageal cancer and that the effect of these polymorphisms was modified by the amount of alcohol consumed. (PMID:17036331)
- ALDH2 genotype affects the genotoxic damage caused by acetaldehyde (PMID:17040107)
- Genetic polymorphisms of ALDH2 is associated with oral and pharyngeal squamous cell carcinoma (PMID:17071628)
- present study revealed that the ALDH2 *1/*1 genotype was significantly associated with the prevalence of multiple lacunar infarcts in Japanese men (PMID:17388993)
- ALDH2 polymorphisms may play an important role in the pathogenesis of MI in elderly Korean men (PMID:17459359)
Cross-species orthologs
8 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | aldh2.2 | ENSDARG00000028087 |
| danio_rerio | aldh2.1 | ENSDARG00000089924 |
| ENSDARG00000099154 | ||
| mus_musculus | Aldh2 | ENSMUSG00000029455 |
| rattus_norvegicus | Aldh2 | ENSRNOG00000073701 |
| drosophila_melanogaster | Aldh | FBGN0012036 |
| caenorhabditis_elegans | WBGENE00000107 | |
| caenorhabditis_elegans | WBGENE00000108 |
Paralogs (17): ALDH3B1 (ENSG00000006534), ALDH3A2 (ENSG00000072210), ALDH3A1 (ENSG00000108602), ALDH5A1 (ENSG00000112294), ALDH8A1 (ENSG00000118514), ALDH6A1 (ENSG00000119711), ALDH1A2 (ENSG00000128918), ALDH3B2 (ENSG00000132746), ALDH1L2 (ENSG00000136010), ALDH1B1 (ENSG00000137124), ALDH9A1 (ENSG00000143149), ALDH1L1 (ENSG00000144908), ALDH4A1 (ENSG00000159423), ALDH16A1 (ENSG00000161618), ALDH7A1 (ENSG00000164904), ALDH1A1 (ENSG00000165092), ALDH1A3 (ENSG00000184254)
Protein
Protein identifiers
Aldehyde dehydrogenase, mitochondrial — P05091 (reviewed: P05091)
Alternative names: ALDH class 2, ALDH-E2, ALDHI
All UniProt accessions (4): A0A384NPN7, P05091, F8VSB0, S4R3S4
UniProt curated annotations — full annotation on UniProt →
Function. Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage.
Subunit / interactions. Homotetramer.
Subcellular location. Mitochondrion matrix.
Post-translational modifications. In response to mitochondrial stress, the precursor protein is ubiquitinated by the SIFI complex in the cytoplasm before mitochondrial import, leading to its degradation. Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1.
Disease relevance. AMED syndrome, digenic (AMEDS) [MIM:619151] A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. AMEDS is an autosomal recessive, digenic form characterized by childhood onset of bone marrow failure resulting in aplastic anemia, in association with global developmental delay, intellectual disability, and poor overall growth with short stature. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. AMEDS patients carry ADH5 biallelic variants and homozygous or heterozygous ALDH2 variant p.Glu504Lys, affecting protein activity. Cellular and animal studies demonstrate that the simultaneous loss of ALDH2 and ADH5 activities leads to an increase of cellular formaldehyde sensitivity and multisystem abnormalities including hematopoietic failure.
Pathway. Alcohol metabolism; ethanol degradation; acetate from ethanol: step 2/2.
Polymorphism. Genetic variation in ALDH2 is responsible for individual differences in responses to drinking alcohol [MIM:610251]. Allele ALDH2*2 is associated with a very high incidence of acute alcohol intoxication in Orientals and South American Indians, as compared to Caucasians.
Similarity. Belongs to the aldehyde dehydrogenase family.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| P05091-1 | 1 | yes |
| P05091-2 | 2 |
RefSeq proteins (2): NP_000681, NP_001191818 (=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR015590 | Aldehyde_DH_dom | Domain |
| IPR016160 | Ald_DH_CS_CYS | Conserved_site |
| IPR016161 | Ald_DH/histidinol_DH | Homologous_superfamily |
| IPR016162 | Ald_DH_N | Homologous_superfamily |
| IPR016163 | Ald_DH_C | Homologous_superfamily |
| IPR029510 | Ald_DH_CS_GLU | Conserved_site |
Pfam: PF00171
Enzyme classification (BRENDA):
- EC 1.2.1.3 — aldehyde dehydrogenase (NAD+) (BRENDA: 46 organisms, 365 substrates, 267 inhibitors, 547 Km, 169 kcat entries)
Substrate kinetics (BRENDA)
128 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| NAD+ | 0.0003–16 | 121 |
| ACETALDEHYDE | 0.0001–80 | 59 |
| PROPANAL | — | 54 |
| BENZALDEHYDE | — | 21 |
| HEXANAL | — | 15 |
| PROPIONALDEHYDE | 0.0028–12 | 15 |
| PHOSPHONOACETALDEHYDE | 0.0032–0.5 | 13 |
| GLYCOLALDEHYDE | 0.005–0.69 | 10 |
| FORMALDEHYDE | 0.031–0.7 | 7 |
| P-NITROBENZALDEHYDE | — | 7 |
| 6-DIMETHYLAMINO-2-NAPHTHALDEHYDE | 0.0017–0.02 | 6 |
| BUTANAL | 0.0002–0.045 | 6 |
| METHYLGLYOXAL | 0.0086–1.876 | 6 |
| NADP+ | 0.27–8.47 | 6 |
| OCTANAL | — | 6 |
Catalyzed reactions (Rhea), 1 shown:
- an aldehyde + NAD(+) + H2O = a carboxylate + NADH + 2 H(+) (RHEA:16185)
UniProt features (80 total): strand 26, helix 19, sequence conflict 12, modified residue 9, sequence variant 3, turn 3, active site 2, transit peptide 1, chain 1, splice variant 1, short sequence motif 1, binding site 1, site 1
Structure
Experimental structures (PDB)
29 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 1O04 | X-RAY DIFFRACTION | 1.42 |
| 3N80 | X-RAY DIFFRACTION | 1.5 |
| 8DR9 | X-RAY DIFFRACTION | 1.5 |
| 3INJ | X-RAY DIFFRACTION | 1.69 |
| 3N81 | X-RAY DIFFRACTION | 1.7 |
| 3INL | X-RAY DIFFRACTION | 1.86 |
| 1O02 | X-RAY DIFFRACTION | 1.9 |
| 3N83 | X-RAY DIFFRACTION | 1.9 |
| 2ONP | X-RAY DIFFRACTION | 2 |
| 1ZUM | X-RAY DIFFRACTION | 2.1 |
| 3SZ9 | X-RAY DIFFRACTION | 2.1 |
| 4KWG | X-RAY DIFFRACTION | 2.1 |
| 1O01 | X-RAY DIFFRACTION | 2.15 |
| 2ONO | X-RAY DIFFRACTION | 2.15 |
| 4FR8 | X-RAY DIFFRACTION | 2.2 |
| 1O05 | X-RAY DIFFRACTION | 2.25 |
| 3N82 | X-RAY DIFFRACTION | 2.25 |
| 4FQF | X-RAY DIFFRACTION | 2.28 |
| 4KWF | X-RAY DIFFRACTION | 2.31 |
| 2VLE | X-RAY DIFFRACTION | 2.4 |
| 5L13 | X-RAY DIFFRACTION | 2.4 |
| 1NZX | X-RAY DIFFRACTION | 2.45 |
| 1NZZ | X-RAY DIFFRACTION | 2.45 |
| 2ONM | X-RAY DIFFRACTION | 2.5 |
| 1CW3 | X-RAY DIFFRACTION | 2.58 |
| 1O00 | X-RAY DIFFRACTION | 2.6 |
| 1NZW | X-RAY DIFFRACTION | 2.65 |
| 8SHS | ELECTRON MICROSCOPY | 2.66 |
| 2ONN | X-RAY DIFFRACTION | 2.75 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P05091-F1 | 96.02 | 0.96 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (3): 285 (proton acceptor); 319 (nucleophile); 186 (transition state stabilizer)
Ligand- & substrate-binding residues (1): 262–267
Post-translational modifications (9): 159, 368, 383, 426, 428, 451, 52, 73, 78
Function
Pathways and Gene Ontology
Reactome pathways
13 pathways
| ID | Pathway |
|---|---|
| R-HSA-380612 | Metabolism of serotonin |
| R-HSA-445355 | Smooth Muscle Contraction |
| R-HSA-71384 | Ethanol oxidation |
| R-HSA-9837999 | Mitochondrial protein degradation |
| R-HSA-112311 | Neurotransmitter clearance |
| R-HSA-112315 | Transmission across Chemical Synapses |
| R-HSA-112316 | Neuronal System |
| R-HSA-1430728 | Metabolism |
| R-HSA-211859 | Biological oxidations |
| R-HSA-211945 | Phase I - Functionalization of compounds |
| R-HSA-380615 | Serotonin clearance from the synaptic cleft |
| R-HSA-392499 | Metabolism of proteins |
| R-HSA-397014 | Muscle contraction |
MSigDB gene sets: 352 (showing top):
VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, JAEGER_METASTASIS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_ALDEHYDE_CATABOLIC_PROCESS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_AMINE_METABOLIC_PROCESS, KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_DOPAMINE_METABOLIC_PROCESS
GO Biological Process (9): carbohydrate metabolic process (GO:0005975), alcohol metabolic process (GO:0006066), ethanol metabolic process (GO:0006067), ethanol catabolic process (GO:0006068), nitroglycerin metabolic process (GO:0018937), aldehyde catabolic process (GO:0046185), cellular detoxification of aldehyde (GO:0110095), regulation of dopamine biosynthetic process (GO:1903179), regulation of serotonin biosynthetic process (GO:1905627)
GO Molecular Function (8): aldehyde dehydrogenase (NAD+) activity (GO:0004029), aldehyde dehydrogenase [NAD(P)+] activity (GO:0004030), phenylacetaldehyde dehydrogenase (NAD+) activity (GO:0008957), electron transfer activity (GO:0009055), NAD binding (GO:0051287), carboxylesterase activity (GO:0106435), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor (GO:0016620)
GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), extracellular exosome (GO:0070062)
Reactome top-level categories
Rollup of top-9 pathways:
| Category | Pathways |
|---|---|
| Serotonin clearance from the synaptic cleft | 1 |
| Muscle contraction | 1 |
| Phase I - Functionalization of compounds | 1 |
| Metabolism of proteins | 1 |
| Transmission across Chemical Synapses | 1 |
| Neuronal System | 1 |
| Metabolism | 1 |
| Biological oxidations | 1 |
| Neurotransmitter clearance | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| regulation of biosynthetic process | 2 |
| primary metabolic process | 1 |
| small molecule metabolic process | 1 |
| primary alcohol metabolic process | 1 |
| ethanol metabolic process | 1 |
| primary alcohol catabolic process | 1 |
| xenobiotic metabolic process | 1 |
| aldehyde metabolic process | 1 |
| catabolic process | 1 |
| cellular response to aldehyde | 1 |
| cellular detoxification | 1 |
| regulation of dopamine metabolic process | 1 |
| dopamine biosynthetic process | 1 |
| serotonin biosynthetic process | 1 |
| aldehyde dehydrogenase [NAD(P)+] activity | 1 |
| oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor | 1 |
| aldehyde dehydrogenase (NAD+) activity | 1 |
| molecular_function | 1 |
| adenyl nucleotide binding | 1 |
| carboxylic ester hydrolase activity | 1 |
| catalytic activity | 1 |
| oxidoreductase activity, acting on the aldehyde or oxo group of donors | 1 |
| cytoplasm | 1 |
| intracellular membrane-bounded organelle | 1 |
| mitochondrion | 1 |
| intracellular organelle lumen | 1 |
| extracellular vesicle | 1 |
Protein interactions and networks
STRING
4280 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| ALDH2 | ADH1B | P00325 | 984 |
| ALDH2 | ADH1C | P00326 | 959 |
| ALDH2 | ADH4 | P08319 | 926 |
| ALDH2 | AVP | P01185 | 923 |
| ALDH2 | ADH1A | P07327 | 907 |
| ALDH2 | ADH7 | P40394 | 890 |
| ALDH2 | ADH6 | P28332 | 878 |
| ALDH2 | ADH5 | P11766 | 877 |
| ALDH2 | CYP2E1 | P05181 | 837 |
| ALDH2 | MAOA | P21397 | 781 |
| ALDH2 | F5H6H0 | F5H6H0 | 780 |
| ALDH2 | ANKK1 | Q8NFD2 | 777 |
| ALDH2 | SLC6A4 | P31645 | 760 |
| ALDH2 | ACO2 | Q99798 | 720 |
| ALDH2 | MAOB | P27338 | 690 |
IntAct
79 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| CFTR | ESYT2 | psi-mi:“MI:2364”(proximity) | 0.710 |
| SERPINB5 | ALDH2 | psi-mi:“MI:0914”(association) | 0.530 |
| COX5B | COX7A2L | psi-mi:“MI:0914”(association) | 0.530 |
| MCRIP2 | CASC3 | psi-mi:“MI:0914”(association) | 0.530 |
| ALDH2 | ALDH1A1 | psi-mi:“MI:0915”(physical association) | 0.490 |
| ALDH1A1 | ALDH2 | psi-mi:“MI:0915”(physical association) | 0.490 |
| ALDH2 | ALDH2 | psi-mi:“MI:0407”(direct interaction) | 0.440 |
| TOP1 | ALDH2 | psi-mi:“MI:0915”(physical association) | 0.400 |
| ALDH2 | SIRT3 | psi-mi:“MI:0915”(physical association) | 0.400 |
| HSPB2 | ALDH2 | psi-mi:“MI:0915”(physical association) | 0.370 |
| ALDH2 | PCNA | psi-mi:“MI:0915”(physical association) | 0.370 |
| RPL13A | ALDH2 | psi-mi:“MI:0915”(physical association) | 0.370 |
| SIRT4 | VWA8 | psi-mi:“MI:0914”(association) | 0.350 |
| JUN | TPM3 | psi-mi:“MI:0914”(association) | 0.350 |
| HSCB | RBP5 | psi-mi:“MI:0914”(association) | 0.350 |
| TNFRSF10A | NAP1L4 | psi-mi:“MI:0914”(association) | 0.350 |
| CUL3 | PXDNL | psi-mi:“MI:0914”(association) | 0.350 |
| LRRK2 | psi-mi:“MI:0914”(association) | 0.350 | |
| SERPINB5 | RAP1BL | psi-mi:“MI:0914”(association) | 0.350 |
| ALDH2 | ALDH1A2 | psi-mi:“MI:0914”(association) | 0.350 |
| COX6B1 | ALDH1L1 | psi-mi:“MI:0914”(association) | 0.350 |
| M | psi-mi:“MI:0914”(association) | 0.350 | |
| NUDT19 | psi-mi:“MI:0914”(association) | 0.350 | |
| PA | DDX39A | psi-mi:“MI:0914”(association) | 0.350 |
| SST | ATP1A2 | psi-mi:“MI:0914”(association) | 0.350 |
| PGR | DDX3X | psi-mi:“MI:0914”(association) | 0.350 |
| MAP3K7 | ACOT7 | psi-mi:“MI:0914”(association) | 0.350 |
| RIPK4 | TBCA | psi-mi:“MI:0914”(association) | 0.350 |
BioGRID (195): ALDH2 (Affinity Capture-MS), IGKC (Affinity Capture-MS), ALDH1A2 (Affinity Capture-MS), ALDH6A1 (Affinity Capture-MS), FGB (Affinity Capture-MS), SERPINA1 (Affinity Capture-MS), TF (Affinity Capture-MS), FGG (Affinity Capture-MS), IGHG1 (Affinity Capture-MS), IGHG3 (Affinity Capture-MS), IGHG4 (Affinity Capture-MS), APOA1 (Affinity Capture-MS), FGA (Affinity Capture-MS), CALML5 (Affinity Capture-MS), ALDH2 (Affinity Capture-MS)
ESM2 similar proteins: A0A2I7G3B0, A6ZR27, C5I9X1, C7A2A0, O14293, O35945, O74187, P00352, P05091, P08157, P11884, P12762, P13601, P15437, P17202, P20000, P24549, P30837, P30841, P40047, P40108, P41751, P42041, P42757, P46367, P47738, P47771, P48644, P51647, P51977, P54114, P54115, P81178, P86886, Q25417, Q27640, Q28399, Q29490, Q2XQV4, Q5R6B5
Diamond homologs: A0A0E3T3B5, A0A0E3T552, A0A2I7G3B0, A0B2F6, A4JJG5, A4VKC2, A4XPI6, A5WA96, A6VEI4, A6ZR27, A8GBX8, A9AN00, B0KN18, B1J2K9, B1JSQ9, B1K708, B1Z033, B2FQ90, B3VMC0, B4EHJ1, B6ECN9, B7V5R4, C0P9J6, C3K3D2, C5I9X1, C6DKY5, C6KEM4, G5DDC2, H8ZPX2, O04895, O14293, O24174, O34660, O35945, O59808, O74187, O93344, O94788, P00352, P05091
SIGNOR signaling
6 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| AMPK | “up-regulates activity” | ALDH2 | phosphorylation |
| PRKAA1 | “up-regulates activity” | ALDH2 | phosphorylation |
| PRKCE | “up-regulates activity” | ALDH2 | phosphorylation |
| ALDH2 | “up-regulates activity” | HDAC3 | binding |
Disease & clinical
Cancer significance
From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — OS.
Clinical variants and AI predictions
ClinVar
56 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 28 |
| Likely benign | 7 |
| Benign | 7 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
2095 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 12:111767098:T:A | donor_loss | 1.0000 |
| 12:111781913:TGTAG:T | acceptor_loss | 1.0000 |
| 12:111781914:GTAGA:G | acceptor_loss | 1.0000 |
| 12:111781915:TAGAT:T | acceptor_loss | 1.0000 |
| 12:111781916:A:AG | acceptor_gain | 1.0000 |
| 12:111781916:A:T | acceptor_loss | 1.0000 |
| 12:111781917:G:A | acceptor_loss | 1.0000 |
| 12:111781917:G:GG | acceptor_gain | 1.0000 |
| 12:111781917:G:GT | acceptor_loss | 1.0000 |
| 12:111781917:GA:G | acceptor_gain | 1.0000 |
| 12:111781917:GAT:G | acceptor_gain | 1.0000 |
| 12:111781917:GATT:G | acceptor_gain | 1.0000 |
| 12:111781917:GATTT:G | acceptor_gain | 1.0000 |
| 12:111783153:TCTAG:T | acceptor_loss | 1.0000 |
| 12:111783154:CTAGG:C | acceptor_loss | 1.0000 |
| 12:111783155:TA:T | acceptor_loss | 1.0000 |
| 12:111783156:A:AG | acceptor_gain | 1.0000 |
| 12:111783156:A:C | acceptor_loss | 1.0000 |
| 12:111783157:G:GC | acceptor_loss | 1.0000 |
| 12:111783157:G:GG | acceptor_gain | 1.0000 |
| 12:111783157:GGA:G | acceptor_gain | 1.0000 |
| 12:111783157:GGAA:G | acceptor_gain | 1.0000 |
| 12:111783294:TGGCG:T | donor_gain | 1.0000 |
| 12:111783295:GGCG:G | donor_gain | 1.0000 |
| 12:111783295:GGCGG:G | donor_gain | 1.0000 |
| 12:111783296:GCG:G | donor_gain | 1.0000 |
| 12:111783296:GCGG:G | donor_gain | 1.0000 |
| 12:111783297:CG:C | donor_gain | 1.0000 |
| 12:111783297:CGG:C | donor_loss | 1.0000 |
| 12:111783298:GG:G | donor_gain | 1.0000 |
AlphaMissense
3375 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 12:111790434:T:A | W185R | 0.999 |
| 12:111790434:T:C | W185R | 0.999 |
| 12:111790439:T:A | N186K | 0.999 |
| 12:111790439:T:G | N186K | 0.999 |
| 12:111790440:T:C | F187L | 0.999 |
| 12:111790442:C:A | F187L | 0.999 |
| 12:111790442:C:G | F187L | 0.999 |
| 12:111799909:T:C | F418L | 0.999 |
| 12:111799911:C:A | F418L | 0.999 |
| 12:111799911:C:G | F418L | 0.999 |
| 12:111803896:T:C | F482L | 0.999 |
| 12:111803898:T:A | F482L | 0.999 |
| 12:111803898:T:G | F482L | 0.999 |
| 12:111803918:G:A | G489E | 0.999 |
| 12:111783215:T:A | W93R | 0.998 |
| 12:111783215:T:C | W93R | 0.998 |
| 12:111791402:T:C | F260L | 0.998 |
| 12:111791404:C:A | F260L | 0.998 |
| 12:111791404:C:G | F260L | 0.998 |
| 12:111792120:G:C | E285D | 0.998 |
| 12:111792120:G:T | E285D | 0.998 |
| 12:111792133:A:C | S290R | 0.998 |
| 12:111792135:C:A | S290R | 0.998 |
| 12:111792135:C:G | S290R | 0.998 |
| 12:111792646:G:T | G316V | 0.998 |
| 12:111792670:G:C | R324P | 0.998 |
| 12:111799913:G:A | G419E | 0.998 |
| 12:111799936:T:C | F427L | 0.998 |
| 12:111799938:C:A | F427L | 0.998 |
| 12:111799938:C:G | F427L | 0.998 |
dbSNP variants (sampled 300 via entrez): RS1000057878 (12:111802832 A>G), RS1000065244 (12:111780341 A>G), RS1000100310 (12:111765123 C>A), RS1000171572 (12:111766663 G>A), RS1000243016 (12:111791683 C>G,T), RS1000256508 (12:111776010 TGGTTCAACAGTGAA>T), RS1000286169 (12:111777914 C>T), RS1000345479 (12:111784627 A>T), RS1000450162 (12:111776838 C>A), RS1000473277 (12:111789319 AC>A), RS1000547909 (12:111810693 G>A), RS1000623830 (12:111790232 C>T), RS1000663123 (12:111814936 C>G), RS1000697021 (12:111770273 C>T), RS1000842354 (12:111807899 CAG>C)
Disease associations
OMIM: gene `` | disease phenotypes: MIM:103780, MIM:610251, MIM:619151
GenCC curated gene-disease
Mondo (3): alcohol dependence (MONDO:0007079), alcohol sensitivity, acute (MONDO:0012454), AMED syndrome, digenic (MONDO:0030894)
Orphanet (1): Aplastic anemia-intellectual disability-dwarfism syndrome (Orphanet:611216)
HPO phenotypes
3 total (3 of 3 shown, HPO-id order):
| HPO | Term |
|---|---|
| HP:0000006 | Autosomal dominant inheritance |
| HP:0001033 | Facial flushing after alcohol intake |
| HP:0003533 | Reduced acetaldehyde dehydrogenase level |
GWAS associations
93 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST000466_1 | Esophageal cancer | 3.000000e-24 |
| GCST000582_4 | Mean corpuscular hemoglobin concentration | 7.000000e-10 |
| GCST000583_16 | Hematological and biochemical traits | 5.000000e-09 |
| GCST000583_24 | Hematological and biochemical traits | 5.000000e-09 |
| GCST000954_1 | Alcohol consumption | 9.000000e-59 |
| GCST000994_1 | Drinking behavior | 4.000000e-211 |
| GCST001011_3 | Oral cavity and pharyngeal cancer | 2.000000e-08 |
| GCST001072_7 | Blood pressure | 8.000000e-31 |
| GCST001074_7 | Blood pressure | 1.000000e-35 |
| GCST001260_3 | Coronary heart disease | 2.000000e-34 |
| GCST001367_3 | Triglycerides | 2.000000e-06 |
| GCST001388_4 | Intracranial aneurysm | 3.000000e-06 |
| GCST001606_4 | Renal function-related traits (sCR) | 3.000000e-10 |
| GCST001706_8 | Stroke (ischemic) | 1.000000e-06 |
| GCST001842_1 | Drinking behavior | 3.000000e-215 |
| GCST001845_2 | Coronary heart disease | 5.000000e-11 |
| GCST002292_1 | Response to alcohol consumption (flushing response) | 5.000000e-26 |
| GCST002293_2 | Alcohol dependence | 5.000000e-08 |
| GCST002294_3 | Alcohol consumption (max-drinks) | 1.000000e-16 |
| GCST002461_2 | Body mass index | 3.000000e-11 |
| GCST002475_4 | Myocardial infarction | 1.000000e-14 |
| GCST002627_12 | Hypertension | 6.000000e-08 |
| GCST002630_13 | Systolic blood pressure | 1.000000e-07 |
| GCST002631_3 | Diastolic blood pressure | 3.000000e-10 |
| GCST003028_2 | Serum alpha1-antitrypsin levels | 2.000000e-23 |
| GCST003043_77 | Inflammatory bowel disease | 1.000000e-08 |
| GCST003044_55 | Crohn’s disease | 7.000000e-08 |
| GCST003129_17 | Primary biliary cholangitis | 3.000000e-08 |
| GCST003217_7 | Triglycerides | 1.000000e-08 |
| GCST003258_1 | Ischemic stroke | 4.000000e-09 |
EFO canonical traits (28, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0004509 | hemoglobin measurement |
| EFO:0004528 | mean corpuscular hemoglobin concentration |
| EFO:0004532 | serum gamma-glutamyl transferase measurement |
| EFO:0004329 | alcohol drinking |
| EFO:0004315 | drinking behavior |
| EFO:0006335 | systolic blood pressure |
| EFO:0006336 | diastolic blood pressure |
| EFO:0004530 | triglyceride measurement |
| EFO:0004340 | body mass index |
| EFO:1001495 | small artery occlusion |
| EFO:0000195 | metabolic syndrome |
| EFO:0006782 | cups of coffee per day measurement |
| EFO:0004761 | uric acid measurement |
| EFO:0007835 | alcohol dependence measurement |
| EFO:0006340 | mean arterial pressure |
| EFO:0004736 | aspartate aminotransferase measurement |
| EFO:0009104 | hyperuricemia |
| EFO:0004531 | urate measurement |
| EFO:0006525 | cigarettes per day measurement |
| EFO:0006781 | coffee consumption measurement |
| EFO:0010091 | tea consumption measurement |
| EFO:0008111 | diet measurement |
| EFO:0010139 | fish consumption measurement |
| EFO:1001504 | small vessel stroke |
| EFO:0010156 | sweet liking measurement |
| EFO:0007788 | BMI-adjusted waist-hip ratio |
| EFO:0009473 | hemolysis |
| EFO:0003939 | energy intake |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (2): CHEMBL1935 (SINGLE PROTEIN), CHEMBL3542434 (PROTEIN FAMILY)
Molecules with ChEMBL bioactivity
3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 141,084 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL964 | DISULFIRAM | 4 | 38,611 |
| CHEMBL120563 | THIRAM | 2 | 79,340 |
| CHEMBL8145 | DAIDZEIN | 2 | 23,133 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
PharmGKB clinical annotations
5 annotations.
| Variant | Type | Level | Drugs | Phenotypes |
|---|---|---|---|---|
| rs671 | Toxicity | 2B | ethanol | Alcohol abuse |
| rs671 | Metabolism/PK | 3 | acetaldehyde | |
| rs671 | Metabolism/PK | 3 | ethanol | |
| rs671 | Other | 3 | heroin | Heroin Dependence |
| rs671 | Efficacy | 3 | naltrexone | Alcohol abuse |
PharmGKB variants
1 variants.
| Variant | Genes | Level | Score | #Clin annots | Drugs |
|---|---|---|---|---|---|
| rs671 | ALDH2 | 2B | 4.75 | 5 | ethanol;acetaldehyde;naltrexone;heroin |
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: enzyme — 1.-.-.- Oxidoreductases
Most potent curated ligand interactions (2 total), top 2:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| prunetin | Inhibition | 6.35 | pKi |
| disulfiram | Inhibition | 4.44 | pIC50 |
Binding affinities (BindingDB)
63 measured of 65 human assays (65 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| tert-butyl N-[1-[3-[2-[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]ethynyl]azetidine-1-carbonyl]cyclopropyl]-N-methylcarbamate | IC50 | 2.3 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-[1-(cyclobutanecarbonyl)azetidin-3-yl]ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 4 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-[1-(cyclopropanecarbonyl)azetidin-3-yl]ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 5 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-[1-(3-hydroxy-3-methylcyclobutanecarbonyl)azetidin-3-yl]ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 5 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-[1-(2,2-difluorocyclopropanecarbonyl)azetidin-3-yl]ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 5 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| tert-butyl N-[1-[3-[2-[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]ethynyl]azetidine-1-carbonyl]cyclopropyl]carbamate | IC50 | 5 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-[1-(3,3-difluorocyclobutanecarbonyl)azetidin-3-yl]ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 6 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-[1-(3-methyloxetane-3-carbonyl)azetidin-3-yl]ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 6 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-[1-(1-methylcyclopropanecarbonyl)azetidin-3-yl]ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 6 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| tert-butyl N-[1-[3-[2-[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]ethynyl]azetidine-1-carbonyl]cyclobutyl]carbamate | IC50 | 6 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-[1-(cyclopropanecarbonyl)piperidin-4-yl]ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 6.5 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[4-oxo-7-[2-(3-propan-2-ylimidazol-4-yl)ethynyl]chromen-3-yl]phenyl]methanesulfonamide | IC50 | 7 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-[1-(3-methoxypropanoyl)azetidin-3-yl]ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 8 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| tert-butyl 3-[2-[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]ethynyl]azetidine-1-carboxylate | IC50 | 9 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[4-oxo-7-[2-(2-oxo-1H-pyridin-4-yl)ethynyl]chromen-3-yl]phenyl]methanesulfonamide | IC50 | 9 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| cyclopentyl 3-[2-[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]ethynyl]azetidine-1-carboxylate | IC50 | 9 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-(2,3-dimethylimidazol-4-yl)ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 15 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-[1-(2-hydroxyacetyl)azetidin-3-yl]ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 15 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-[1-(2-hydroxypropanoyl)azetidin-3-yl]ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 15 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 16 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[4-oxo-7-(2-pyridin-3-ylethynyl)chromen-3-yl]phenyl]methanesulfonamide | IC50 | 21 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| 2-chloro-6-methyl-N-[[4-(2-oxo-1H-pyridin-4-yl)phenyl]methyl]benzamide | IC50 | 23 nM | US-9000015: Compounds for the treatment of addiction |
| 2,6-dichloro-N-[[4-(5-fluoro-2-oxo-1H-pyridin-4-yl)phenyl]methyl]benzamide | IC50 | 25 nM | US-9000015: Compounds for the treatment of addiction |
| N-[4-[7-[2-[1-(1-methylpiperidine-4-carbonyl)azetidin-3-yl]ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 35 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-(oxan-4-yl)ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 43 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-(3-methoxyprop-1-ynyl)-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 47 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[4-oxo-7-(2-pyrimidin-5-ylethynyl)chromen-3-yl]phenyl]methanesulfonamide | IC50 | 57 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-(2-cyclopropylethynyl)-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 57.7 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| 2,6-dichloro-4-(2-methoxyethoxy)-N-[[4-(2-oxo-1H-pyridin-4-yl)phenyl]methyl]benzamide | IC50 | 63 nM | US-9000015: Compounds for the treatment of addiction |
| N-[4-[7-[2-[1-[3-(dimethylamino)propanoyl]azetidin-3-yl]ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 64 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| tert-butyl 4-[2-[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]ethynyl]piperidine-1-carboxylate | IC50 | 86 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[4-oxo-7-(2-pyridin-2-ylethynyl)chromen-3-yl]phenyl]methanesulfonamide | IC50 | 90 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-(1-methylimidazol-4-yl)ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 95 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-(3-methoxyprop-1-ynyl)-4-oxochromen-3-yl]phenyl]cyclopropanesulfonamide | IC50 | 96 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| 2,6-dichloro-N-[[4-(2-oxo-1H-pyridin-4-yl)phenyl]methyl]benzamide | IC50 | 102 nM | US-9000015: Compounds for the treatment of addiction |
| 1-(2-methylpropyl)-3-[2-[4-oxo-3-[4-[(sulfinatoamino)methyl]phenyl]chromen-7-yl]ethynyl]azetidine | IC50 | 109 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| N-[4-[7-[2-(1-hydroxycyclopentyl)ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 156 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| 2,6-dimethyl-N-[[4-(2-oxo-1H-pyridin-4-yl)phenyl]methyl]benzamide | IC50 | 166 nM | US-9000015: Compounds for the treatment of addiction |
| N-[4-[4-oxo-7-(2-piperidin-4-ylethynyl)chromen-3-yl]phenyl]methanesulfonamide | IC50 | 174 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| 2-chloro-3-fluoro-N-[[4-(2-oxo-1H-pyridin-4-yl)phenyl]methyl]benzamide | IC50 | 215 nM | US-9000015: Compounds for the treatment of addiction |
| N-[4-[7-[2-(azetidin-3-yl)ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 266 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| 2,6-dichloro-N-[[2-fluoro-4-(2-oxo-1H-pyridin-4-yl)phenyl]methyl]benzamide | IC50 | 304 nM | US-9000015: Compounds for the treatment of addiction |
| N-[4-[4-oxo-7-(2-phenylethynyl)chromen-3-yl]phenyl]methanesulfonamide | IC50 | 329 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| 2-chloro-6-fluoro-N-[[4-(2-oxo-1H-pyridin-4-yl)phenyl]methyl]benzamide | IC50 | 379 nM | US-9000015: Compounds for the treatment of addiction |
| 7-[2-(1-hydroxycyclopentyl)ethynyl]-4-oxo-3-[4-[(sulfinatoamino)methyl]phenyl]chromene | IC50 | 386 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| 2-chloro-3,6-difluoro-N-[[4-(2-oxo-1H-pyridin-4-yl)phenyl]methyl]benzamide | IC50 | 464 nM | US-9000015: Compounds for the treatment of addiction |
| 2,6-dichloro-N-[[3-methyl-4-(2-oxo-1H-pyridin-4-yl)phenyl]methyl]benzamide | IC50 | 480 nM | US-9000015: Compounds for the treatment of addiction |
| N-[4-[7-[2-(1-aminocyclohexyl)ethynyl]-4-oxochromen-3-yl]phenyl]methanesulfonamide | IC50 | 528 nM | US-8673966: ALDH-2 inhibitors in the treatment of addiction |
| ethyl 2-[3-hydroxy-2-oxo-3-(2-oxo-2-pyridin-4-ylethyl)indol-1-yl]acetate | IC50 | 800 nM | US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods |
| 2,6-difluoro-N-[[4-(2-oxo-1H-pyridin-4-yl)phenyl]methyl]benzamide | IC50 | 890 nM | US-9000015: Compounds for the treatment of addiction |
ChEMBL bioactivities
200 potent at pChembl≥5 of 213 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
PubChem BioAssay actives
115 with measured affinity, of 462 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 11-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyundecanoic acid | 31427: Inhibition of Hamster Liver mitochondrial ALDH-2 | ic50 | 0.0030 | uM |
| 10-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxydecanoic acid | 31427: Inhibition of Hamster Liver mitochondrial ALDH-2 | ic50 | 0.0040 | uM |
| 6-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyhexanoic acid | 31427: Inhibition of Hamster Liver mitochondrial ALDH-2 | ic50 | 0.0090 | uM |
| 7-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyheptanoic acid | 31427: Inhibition of Hamster Liver mitochondrial ALDH-2 | ic50 | 0.0090 | uM |
| 2,3,5-trimethyl-6-propylfuro[3,2-g]chromen-7-one | 1441758: Competitive inhibition of full length recombinant human ALDH2 expressed in Escherichia coli assessed as reduction in dehydrogenase activity using propionaldehyde as substrate in presence of varying levels NAD+ by Lineweaver-Burk plot analysis | ki | 0.0190 | uM |
| 2,3,5,6-tetramethylfuro[3,2-g]chromen-7-one | 1441761: Non-competitive inhibition of full length recombinant human ALDH2 expressed in Escherichia coli assessed as reduction in dehydrogenase activity using varying levels of propionaldehyde as substrate in presence of NAD+ by Lineweaver-Burk plot analysis | ki | 0.0350 | uM |
| 7-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]-3-(4-hydroxyphenyl)chromen-4-one | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.0400 | uM |
| 3-(4-hydroxyphenyl)-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one | 31427: Inhibition of Hamster Liver mitochondrial ALDH-2 | ic50 | 0.0400 | uM |
| 8-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyoctanoic acid | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.0400 | uM |
| 7-ethoxy-3-(4-hydroxyphenyl)chromen-4-one | 31427: Inhibition of Hamster Liver mitochondrial ALDH-2 | ic50 | 0.0400 | uM |
| 5-bromo-1-(2-phenylethyl)indole-2,3-dione | 1074883: Inhibition of human ALDH2 using propionaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NAD+ | ic50 | 0.0500 | uM |
| 13,14-dimethyl-8,12-dioxatetracyclo[7.7.0.02,6.011,15]hexadeca-1(9),2(6),10,13,15-pentaen-7-one | 1441738: Inhibition of full length recombinant human ALDH2 expressed in Escherichia coli assessed as reduction in dehydrogenase activity by measuring NAD(P)H level preincubated for 2 mins followed by addition of propionaldehyde as substrate in presence of NAD+ by spectrophotometric method | ic50 | 0.0670 | uM |
| 9,10-dimethyl-1,2,3,4-tetrahydro-[1]benzofuro[6,5-c]isochromen-5-one | 1441738: Inhibition of full length recombinant human ALDH2 expressed in Escherichia coli assessed as reduction in dehydrogenase activity by measuring NAD(P)H level preincubated for 2 mins followed by addition of propionaldehyde as substrate in presence of NAD+ by spectrophotometric method | ic50 | 0.0670 | uM |
| 7-(2-hydroxyethoxy)-3-(4-hydroxyphenyl)chromen-4-one | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.0700 | uM |
| 3-(4-hydroxyphenyl)-7-propan-2-yloxychromen-4-one | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.0800 | uM |
| 7-(2,3-dihydroxypropoxy)-3-(4-hydroxyphenyl)chromen-4-one | 31428: Compound was evaluated for the inhibition of Hamster Liver mitochondrial ALDH-2 | ic50 | 0.1000 | uM |
| 5-chloro-1-[(E)-3-phenylprop-2-enyl]indole-2,3-dione | 1074883: Inhibition of human ALDH2 using propionaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NAD+ | ic50 | 0.1000 | uM |
| 7-(6-aminohexoxy)-3-(4-hydroxyphenyl)chromen-4-one | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.1000 | uM |
| 5-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxypentanoic acid | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.1000 | uM |
| 7-(6-hydroxyhexoxy)-3-(4-hydroxyphenyl)chromen-4-one | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.1200 | uM |
| ethyl 2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyacetate | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.1300 | uM |
| 12-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxydodecanoic acid | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.1300 | uM |
| 7-hex-5-enoxy-3-(4-hydroxyphenyl)chromen-4-one | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.1500 | uM |
| 7-chloro-4-methyl-3-phenyl-4a,5,6,7,8,8a-hexahydrochromen-2-one | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.1500 | uM |
| 9,10-dimethyl-[1]benzofuro[6,5-c]isochromen-5-one | 1441738: Inhibition of full length recombinant human ALDH2 expressed in Escherichia coli assessed as reduction in dehydrogenase activity by measuring NAD(P)H level preincubated for 2 mins followed by addition of propionaldehyde as substrate in presence of NAD+ by spectrophotometric method | ic50 | 0.1500 | uM |
| 3,4,8,9-tetramethylfuro[2,3-f]chromen-7-one | 1441738: Inhibition of full length recombinant human ALDH2 expressed in Escherichia coli assessed as reduction in dehydrogenase activity by measuring NAD(P)H level preincubated for 2 mins followed by addition of propionaldehyde as substrate in presence of NAD+ by spectrophotometric method | ic50 | 0.1500 | uM |
| 3-(4-hydroxyphenyl)-7-prop-2-enoxychromen-4-one | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.1800 | uM |
| 2,2-dichloro-N-[8-[(2,2-dichloroacetyl)amino]octyl]acetamide | 1418961: Inhibition of N-terminal His6-tagged recombinant human mitochondrial ALDH2 using propionaldehyde as substrate preincubated for 20 mins to 1 hr followed by substrate addition and measured for 5 mins in presence of NADH by fluorescence assay | ic50 | 0.2293 | uM |
| ethyl 5-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxypentanoate | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.2400 | uM |
| 7-(4-aminobutoxy)-3-(4-hydroxyphenyl)chromen-4-one | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.2500 | uM |
| 7-(3-bromopropoxy)-3-(4-hydroxyphenyl)chromen-4-one | 31427: Inhibition of Hamster Liver mitochondrial ALDH-2 | ic50 | 0.2600 | uM |
| 7-(4-bromobutoxy)-3-(4-hydroxyphenyl)chromen-4-one | 31427: Inhibition of Hamster Liver mitochondrial ALDH-2 | ic50 | 0.2700 | uM |
| ethyl 6-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyhexanoate | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.2800 | uM |
| 7-(6-bromohexoxy)-3-(4-hydroxyphenyl)chromen-4-one | 31427: Inhibition of Hamster Liver mitochondrial ALDH-2 | ic50 | 0.3000 | uM |
| methyl 2-(4-methyl-2-oxochromen-7-yl)oxypropanoate | 1441758: Competitive inhibition of full length recombinant human ALDH2 expressed in Escherichia coli assessed as reduction in dehydrogenase activity using propionaldehyde as substrate in presence of varying levels NAD+ by Lineweaver-Burk plot analysis | ki | 0.3100 | uM |
| ethyl 2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxypropanoate | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.3200 | uM |
| dimethylcarbamothioylsulfanyl N,N-dimethylcarbamodithioate | 1762211: Inhibition of ALDH2 (unknown origin) | ic50 | 0.3200 | uM |
| 3,5-dimethyl-6-propylfuro[3,2-g]chromen-7-one | 1441738: Inhibition of full length recombinant human ALDH2 expressed in Escherichia coli assessed as reduction in dehydrogenase activity by measuring NAD(P)H level preincubated for 2 mins followed by addition of propionaldehyde as substrate in presence of NAD+ by spectrophotometric method | ic50 | 0.3400 | uM |
| 2,3-dimethyl-5-propylfuro[3,2-g]chromen-7-one | 1441738: Inhibition of full length recombinant human ALDH2 expressed in Escherichia coli assessed as reduction in dehydrogenase activity by measuring NAD(P)H level preincubated for 2 mins followed by addition of propionaldehyde as substrate in presence of NAD+ by spectrophotometric method | ic50 | 0.3600 | uM |
| 7-[2-(1,3-dioxan-2-yl)ethoxy]-3-(4-hydroxyphenyl)chromen-4-one | 31427: Inhibition of Hamster Liver mitochondrial ALDH-2 | ic50 | 0.4000 | uM |
| 5-chloro-1-(2-phenylethyl)indole-2,3-dione | 1074883: Inhibition of human ALDH2 using propionaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NAD+ | ic50 | 0.4100 | uM |
| 5-hydroxy-3-(4-hydroxyphenyl)-7-methoxychromen-4-one | 341734: Inhibition of human recombinant ALDH2 | ki | 0.4500 | uM |
| 4-methyl-6,7-dihydropyrano[3,2-g]chromene-2,8-dione | 1441738: Inhibition of full length recombinant human ALDH2 expressed in Escherichia coli assessed as reduction in dehydrogenase activity by measuring NAD(P)H level preincubated for 2 mins followed by addition of propionaldehyde as substrate in presence of NAD+ by spectrophotometric method | ic50 | 0.4700 | uM |
| 7-(9-hydroxynonoxy)-3-(4-hydroxyphenyl)chromen-4-one | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 0.7000 | uM |
| cyclopropyl-[4-[[1-[(3-methylphenyl)methyl]benzimidazol-2-yl]methyl]piperazin-1-yl]methanone | 1766111: Inhibition of human ALDH2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometry | ic50 | 0.7900 | uM |
| 3-[[[2-carboxyethyl(ethyl)carbamothioyl]disulfanyl]carbothioyl-ethylamino]propanoic acid | 1762211: Inhibition of ALDH2 (unknown origin) | ic50 | 0.8500 | uM |
| [4-[(5-bromo-2,3-dioxoindol-1-yl)methyl]phenyl]methyl carbamimidoselenoate;hydrobromide | 1702903: Inhibition of ALDH2 (unknown origin) assessed as NADH formation using acetaldehyde as substrate | ic50 | 0.9390 | uM |
| 2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyhexanoic acid | 34047: Inhibition of hamster liver aldehyde dehydrogenase ALDH-2 | ic50 | 1.0000 | uM |
| 7-bromo-5-methyl-1H-indole-2,3-dione | 1074877: Inhibition of human ALDH2 using propionaldehyde as substrate by Lineweaver-Burk plot analysis | ki | 1.0000 | uM |
| 2,3,5-trimethyl-6-(3-oxo-3-piperidin-1-ylpropyl)furo[3,2-g]chromen-7-one | 1441758: Competitive inhibition of full length recombinant human ALDH2 expressed in Escherichia coli assessed as reduction in dehydrogenase activity using propionaldehyde as substrate in presence of varying levels NAD+ by Lineweaver-Burk plot analysis | ki | 1.1000 | uM |
CTD chemical–gene interactions
134 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Acetaldehyde | affects response to substance, decreases metabolic processing, affects metabolic processing, increases chemical synthesis, increases metabolic processing (+4 more) | 12 |
| Ethanol | affects response to substance, decreases expression, decreases reaction, decreases phosphorylation, increases activity (+9 more) | 11 |
| Nitroglycerin | affects metabolic processing, affects reaction, decreases abundance, decreases activity, decreases metabolic processing (+2 more) | 5 |
| Valproic Acid | decreases expression, affects expression, increases expression, affects cotreatment | 5 |
| Cyclosporine | increases expression, decreases expression | 5 |
| propionaldehyde | decreases reaction, increases reaction, affects metabolic processing, increases metabolic processing, increases oxidation | 4 |
| bisphenol A | affects expression, decreases methylation, increases expression | 4 |
| sodium arsenite | increases expression | 4 |
| NAD | decreases activity, decreases reaction, decreases expression, affects binding, affects cotreatment (+1 more) | 4 |
| trichostatin A | affects cotreatment, decreases expression | 3 |
| Air Pollutants | decreases expression, increases expression, increases abundance | 3 |
| Formaldehyde | increases metabolic processing, affects metabolic processing, decreases reaction | 3 |
| Tetrachlorodibenzodioxin | increases expression | 3 |
| sulforaphane | affects reaction, increases expression | 2 |
| enilconazole | decreases expression, affects cotreatment, decreases activity | 2 |
| butyraldehyde | affects metabolic processing, decreases expression | 2 |
| 4-hydroxy-2-nonenal | increases abundance, increases oxidation, affects binding, decreases activity, decreases reaction | 2 |
| benzaldehyde | increases metabolic processing, affects binding, decreases reaction | 2 |
| N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide | affects cotreatment, decreases activity, decreases expression, decreases reaction, increases activity | 2 |
| Resveratrol | affects cotreatment, increases expression, increases reaction | 2 |
| Vorinostat | affects cotreatment, decreases expression | 2 |
| Benzo(a)pyrene | decreases expression, decreases methylation, increases methylation | 2 |
| Lead | decreases expression, decreases reaction, affects abundance, affects reaction, affects cotreatment (+1 more) | 2 |
| Plant Extracts | affects cotreatment, increases expression, decreases reaction, increases abundance | 2 |
| Retinaldehyde | affects cotreatment, increases oxidation, increases metabolic processing | 2 |
| Rotenone | decreases reaction, increases abundance, increases activity, increases expression, decreases expression | 2 |
| Smoke | increases abundance, affects response to substance, decreases expression | 2 |
| Tobacco Smoke Pollution | affects expression, decreases expression | 2 |
| Tretinoin | decreases expression, increases expression | 2 |
| Aflatoxin B1 | decreases expression | 2 |
ChEMBL screening assays
71 unique, capped per target: 66 binding, 5 functional
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1019409 | Binding | Activation of human ALDH2 assessed as phosphorylated enzyme at 20 uM in absence of rat PKCepsilon by spectrophotometry | Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. — Science |
| CHEMBL641178 | Functional | Compound was evaluated for the inhibition of Hamster Liver mitochondrial ALDH-2 | The mitochondrial monoamine oxidase-aldehyde dehydrogenase pathway: a potential site of action of daidzin. — J Med Chem |
Cellosaurus cell lines
18 cell lines: 8 induced pluripotent stem cell, 4 cancer cell line, 3 finite cell line, 3 transformed cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_B0YR | Abcam SW480 ALDH2 KO | Cancer cell line | Male |
| CVCL_B5LY | AP57P | Finite cell line | Male |
| CVCL_B5LZ | AP57P(SVT) | Transformed cell line | Male |
| CVCL_B5M0 | FA50P | Finite cell line | Female |
| CVCL_B5M1 | FA50P-iPSC#1 | Induced pluripotent stem cell | Female |
| CVCL_B5M2 | AP39P-iPSC#1 | Induced pluripotent stem cell | Female |
| CVCL_B5M3 | FA50P-iPSC#2 | Induced pluripotent stem cell | Female |
| CVCL_B5M4 | AP39P-iPSC#2 | Induced pluripotent stem cell | Female |
| CVCL_D8HB | Ubigene HCT 116 ALDH2 KO | Cancer cell line | Male |
| CVCL_E0TK | Ubigene Hep G2 ALDH2 KO | Cancer cell line | Male |
Clinical trials (associated diseases)
300 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT00000437 | PHASE4 | COMPLETED | Tobacco Dependence in Alcoholism Treatment (Nicotine Patch/Naltrexone) |
| NCT00000438 | PHASE4 | COMPLETED | Naltrexone Treatment for Alcoholism |
| NCT00000441 | PHASE4 | COMPLETED | Drug Therapy for Alcohol Detoxification |
| NCT00000442 | PHASE4 | COMPLETED | Naltrexone for Relapse Prevention |
| NCT00000444 | PHASE4 | COMPLETED | Timing of Smoking Intervention in Alcohol Treatment (Nicotine Patch) |
| NCT00000445 | PHASE4 | COMPLETED | Use of Naltrexone in a Clinical Setting |
| NCT00000447 | PHASE4 | COMPLETED | Behavioral/Drug Therapy for Alcohol-Nicotine Dependence (Naltrexone/Nicotine Patch) |
| NCT00000448 | PHASE4 | COMPLETED | Naltrexone Treatment for Alcoholic Women |
| NCT00000449 | PHASE4 | COMPLETED | Behavior and Naltrexone Treatment for Alcoholics |
| NCT00000450 | PHASE4 | COMPLETED | Naltrexone Maintenance Treatment of Alcoholism |
| NCT00000452 | PHASE4 | COMPLETED | Naltrexone Treatment of Alcohol Dependence |
| NCT00000454 | PHASE4 | COMPLETED | Smoking Cessation in Alcoholism Treatment |
| NCT00000455 | PHASE4 | COMPLETED | Naltrexone for Early Problem Drinkers |
| NCT00000456 | PHASE4 | COMPLETED | Behavioral Therapy Plus Naltrexone for Alcoholism |
| NCT00004551 | PHASE4 | COMPLETED | Behavioral Counseling for Alcohol Dependent Smokers (Nicotine Patch) |
| NCT00004554 | PHASE4 | COMPLETED | Sertraline for Alcohol Dependence and Depression |
| NCT00006203 | PHASE4 | COMPLETED | Naltrexone, Craving, and Drinking |
| NCT00006204 | PHASE4 | COMPLETED | Drug Treatment for Depressed Alcoholics (Naltrexone/Fluoxetine) |
| NCT00006449 | PHASE4 | COMPLETED | Post-Treatment Effects of Naltrexone |
| NCT00006489 | PHASE4 | COMPLETED | Treatment for Alcoholism and Post-Traumatic Stress Disorder (Naltrexone) |
| NCT00018824 | PHASE4 | COMPLETED | Treating Alcohol Use In Older Adults With Depression |
| NCT00044434 | PHASE4 | COMPLETED | Bupropion as a Smoking Cessation Aid in Alcoholics |
| NCT00064844 | PHASE4 | COMPLETED | Combination Nicotine Replacement for Alcoholic Smokers |
| NCT00082199 | PHASE4 | COMPLETED | Study of Aripiprazole in Subjects With Alcoholism |
| NCT00115037 | PHASE4 | COMPLETED | Managing Alcoholism in People Who Do Not Respond to Naltrexone |
| NCT00120601 | PHASE4 | UNKNOWN | Trial for the Treatment of Alcohol Dependence |
| NCT00145847 | PHASE4 | COMPLETED | Naltrexone Treatment of Alcohol Abuse in Schizophrenia |
| NCT00148031 | PHASE4 | COMPLETED | Improving Hepatitis C Treatment in Injection Drug Users |
| NCT00159107 | PHASE4 | COMPLETED | Integrative Therapy in Alcoholism |
| NCT00167687 | PHASE4 | COMPLETED | Prazosin Alcohol Dependence IVR Study |
| NCT00223275 | PHASE4 | COMPLETED | Naltrexone for Bipolar Disorder and Alcohol Dependence |
| NCT00226109 | PHASE4 | SUSPENDED | Clinical Trial Studying the Effects of Spironolactone on Heart and Skeletal Muscle Function in Chronic Alcoholics |
| NCT00246441 | PHASE4 | COMPLETED | Paroxetine for Comorbid Social Anxiety Disorder and Alcoholism |
| NCT00249379 | PHASE4 | TERMINATED | Study of Acamprosate to Prevent Alcohol Relapse in Criminal Justice Supervisees |
| NCT00261872 | PHASE4 | COMPLETED | Treatment of Patients With Alcoholism and Attention Deficit Disorder |
| NCT00317031 | PHASE4 | COMPLETED | Individually Adapted Therapy of Alcoholism |
| NCT00325182 | PHASE4 | COMPLETED | The Effects of Levetiracetam on Alcohol Dependent Subjects |
| NCT00329407 | PHASE4 | COMPLETED | The Effects of Topiramate on Alcohol Use in Alcohol Dependent Subjects |
| NCT00330174 | PHASE4 | COMPLETED | Acamprosate in Alcoholics With Comorbid Anxiety or Depression |
| NCT00352469 | PHASE4 | COMPLETED | Trial of Seroquel SR for Alcohol Dependence and Comorbid Anxiety |
Related Atlas pages
- Targeted by drugs: Disulfiram
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): alcohol dependence, alcohol sensitivity, acute, AMED syndrome, digenic, brain aneurysm, carcinoma of esophagus, primary biliary cholangitis, upper aerodigestive tract neoplasm