Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTB6UM0)

• DTT Name: Fatty aldehyde dehydrogenase (ALDH3A2)
• Synonyms: Microsomal aldehyde dehydrogenase; Aldehyde dehydrogenase family 3 member A2; Aldehyde dehydrogenase 10; ALDH10
• Gene Name: ALDH3A2
• DTT Type: Successful target; [1]
• Related Disease: Substance abuse [ICD-11: 6C40]
• BioChemical Class: Aldehyde/oxo donor oxidoreductase
• UniProt ID: AL3A2_HUMAN
• TTD ID: T65291
• EC Number: EC 1.2.1.3
• Sequence:
  MELEVRRVRQAFLSGRSRPLRFRLQQLEALRRMVQEREKDILTAIAADLCKSEFNVYSQE
  VITVLGEIDFMLENLPEWVTAKPVKKNVLTMLDEAYIQPQPLGVVLIIGAWNYPFVLTIQ
  PLIGAIAAGNAVIIKPSELSENTAKILAKLLPQYLDQDLYIVINGGVEETTELLKQRFDH
  IFYTGNTAVGKIVMEAAAKHLTPVTLELGGKSPCYIDKDCDLDIVCRRITWGKYMNCGQT
  CIAPDYILCEASLQNQIVWKIKETVKEFYGENIKESPDYERIINLRHFKRILSLLEGQKI
  AFGGETDEATRYIAPTVLTDVDPKTKVMQEEIFGPILPIVPVKNVDEAINFINEREKPLA
  LYVFSHNHKLIKRMIDETSSGGVTGNDVIMHFTLNSFPFGGVGSSGMGAYHGKHSFDTFS
  HQRPCLLKSLKREGANKLRYPPNSQSKVDWGKFFLLKRFNKEKLGLLLLTFLGIVAAVLV
  KAEYY
• Function: Catalyzes the oxidation of medium and long chain aliphatic aldehydes to fatty acids. Active on a variety of saturated and unsaturated aliphatic aldehydes between 6 and 24 carbons in length. Responsible for conversion of the sphingosine 1-phosphate (S1P) degradation product hexadecenal to hexadecenoic acid.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  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)
  Pantothenate and CoA biosynthesis (hsa00770)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
  Alcoholic liver disease (hsa04936)
• Reactome Pathway:
  Alpha-oxidation of phytanate (R-HSA-389599)
  Class I peroxisomal membrane protein import (R-HSA-9603798)
  Insertion of tail-anchored proteins into the endoplasmic reticulum membrane (R-HSA-9609523)
  RND2 GTPase cycle (R-HSA-9696270)
  RND1 GTPase cycle (R-HSA-9696273)
  Sphingolipid de novo biosynthesis (R-HSA-1660661)
• BioCyc Pathway: MetaCyc:HS01061-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Disulfiram	DMCL2OK	Alcohol dependence	6C40.2	Approved	[1]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NPS 1776	DM0CF3B	Epilepsy	8A60-8A68	Discontinued in Phase 2	[2]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aloe-emodin	DMPTY8S	Discovery agent	N.A.	Investigative	[3]
NSC-527035	DMY689Z	Discovery agent	N.A.	Investigative	[4]
S-methyl 4-methyl-4-morpholinopent-2-ynethioate	DM79QC2	Discovery agent	N.A.	Investigative	[5]

References

• [1] Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Pharmacol Ther. 2006 Sep;111(3):855-76.
• [2] Diverse Mechanisms of Antiepileptic Drugs in the Development Pipeline. Epilepsy Res. 2006 June; 69(3): 273-294.
• [3] Elgonica-Dimers A and B, Two Potent Alcohol Metabolism Inhibitory Constituents of Aloe arborescens J. Nat. Prod. 60(11):1180-1182 (1997).
• [4] Exploring the structural requirements for inhibition of the ubiquitin E3 ligase breast cancer associated protein 2 (BCA2) as a treatment for breast... J Med Chem. 2010 Apr 8;53(7):2757-65.
• [5] Aldehyde dehydrogenase inhibitors: alpha,beta-acetylenic N-substituted aminothiolesters are reversible growth inhibitors of normal epithelial but i... Eur J Med Chem. 2008 May;43(5):906-16.