Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTFLN4T)

• DTT Name: Mitochondrial aldehyde dehydrogenase (ALDH2)
• Synonyms: Aldehyde dehydrogenase, mitochondrial; ALDM; ALDHI; ALDH-E2; ALDH class 2
• Gene Name: ALDH2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Aldehyde/oxo donor oxidoreductase
• UniProt ID: ALDH2_HUMAN
• TTD ID: T44282
• EC Number: EC 1.2.1.3
• Sequence:
  MLRAAARFGPRLGRRLLSAAATQAVPAPNQQPEVFCNQIFINNEWHDAVSRKTFPTVNPS
  TGEVICQVAEGDKEDVDKAVKAARAAFQLGSPWRRMDASHRGRLLNRLADLIERDRTYLA
  ALETLDNGKPYVISYLVDLDMVLKCLRYYAGWADKYHGKTIPIDGDFFSYTRHEPVGVCG
  QIIPWNFPLLMQAWKLGPALATGNVVVMKVAEQTPLTALYVANLIKEAGFPPGVVNIVPG
  FGPTAGAAIASHEDVDKVAFTGSTEIGRVIQVAAGSSNLKRVTLELGGKSPNIIMSDADM
  DWAVEQAHFALFFNQGQCCCAGSRTFVQEDIYDEFVERSVARAKSRVVGNPFDSKTEQGP
  QVDETQFKKILGYINTGKQEGAKLLCGGGIAADRGYFIQPTVFGDVQDGMTIAKEEIFGP
  VMQILKFKTIEEVVGRANNSTYGLAAAVFTKDLDKANYLSQALQAGTVWVNCYDVFGAQS
  PFGGYKMSGSGRELGEYGLQAYTEVKTVTVKVPQKNS
• Function: Second enzyme of the major oxidative pathway of alcohol metabolism. Catalyzes the chemical transformation from acetaldehyde to acetic acid. Additionally, functions as a protector against oxidative stress.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Pentose and glucuronate interconversions (hsa00040)
  Ascorbate and aldarate metabolism (hsa00053)
  Fatty acid degradation (hsa00071)
  Valine, leucine and isoleucine degradation (hsa00280)
  Lysine degradation (hsa00310)
  Arginine and proline metabolism (hsa00330)
  Histidine metabolism (hsa00340)
  Tryptophan metabolism (hsa00380)
  beta-Alanine metabolism (hsa00410)
  Glycerolipid metabolism (hsa00561)
  Pyruvate metabolism (hsa00620)
  Metabolic pathways (hsa01100)
  Biosynthesis of antibiotics (hsa01130)
• Reactome Pathway:
  Ethanol oxidation (R-HSA-71384)
  Metabolism of serotonin (R-HSA-380612)
• BioCyc Pathway: MetaCyc:MON66-302

Molecular Interaction Atlas (MIA) of This DTT

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ALD-401	DM2U530	Cerebrovascular ischaemia	8B1Z	Phase 2	[1]
ANS-6637	DM39QWN	Substance use disorder	6C4Z	Phase 1	[2]
FP-045	DMV9FTH	Cardiovascular disease	BA00-BE2Z	Phase 1	[3]
GS-6637	DMXG3T1	Substance use disorder	6C4Z	Phase 1	[4]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Daidzin	DMFCMPS	N. A.	N. A.	Terminated	[5]

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
crotylaldehyde	DMTWRQI	Discovery agent	N.A.	Investigative	[5]
CVT-10216	DMDH6PJ	Alcohol dependence	6C40.2	Investigative	[6]
ISOFORMONENTIN	DM5CMA8	Discovery agent	N.A.	Investigative	[7]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	N. A.	N. A.	Investigative	[5]
prunetin	DMPD41Q	Discovery agent	N.A.	Investigative	[7]

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Aldehyde dehydrogenase 2 (ALDH2) DME Info
• Gene Name: ALDH2

5 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amyl nitrite	DMJKO05	Angina pectoris	BA40	Approved	[8]
Benzyl alcohol	DMBVYDI	Head and body lice	1G00.0	Approved	[9]
Paraldehyde	DMOC1BX	Insomnia	7A00-7A0Z	Approved	[10]
Pentaerythritol tetranitrate	DMZ9MO5	Angina pectoris	BA40	Approved	[11]
SILODOSIN	DMJSBT6	Benign prostatic hyperplasia	GA90	Approved	[12]

References

• [1] A novel aldehyde dehydrogenase-3 activator leads to adult salivary stem cell enrichment in vivo. Clin Cancer Res. 2011 Dec 1;17(23):7265-72.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Clinical pipeline report, company report or official report of Gilead.
• [5] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2595).
• [7] Structure of daidzin, a naturally occurring anti-alcohol-addiction agent, in complex with human mitochondrial aldehyde dehydrogenase. J Med Chem. 2008 Aug 14;51(15):4482-7.
• [8] Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat. Am J Physiol Heart Circ Physiol. 2010 Sep;299(3):H819-26.
• [9] Effects of ALDH2, CYP1A1, and CYP2E1 genetic polymorphisms and smoking and drinking habits on toluene metabolism in humans. Toxicol Appl Pharmacol. 1995 Aug;133(2):295-304.
• [10] Paraldehyde. J Appl Toxicol. 1991 Oct;11(5):379-81.
• [11] OSHA Occupational Chemical Database: drug information.
• [12] Pharmacokinetics and disposition of silodosin (KMD-3213). Yakugaku Zasshi. 2006 Mar;126 Spec no.:237-45.