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Alda-1

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Organic compound

Pharmaceutical compound
Alda-1
Identifiers
IUPAC name
  • N-(1,3-Benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide
CAS Number
PubChem CID
ChemSpider
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC15H11Cl2NO3
Molar mass324.16 g·mol
3D model (JSmol)
SMILES
  • Clc1cccc(Cl)c1C(=O)NCc2cc3OCOc3cc2
InChI
  • InChI=1S/C15H11Cl2NO3/c16-10-2-1-3-11(17)14(10)15(19)18-7-9-4-5-12-13(6-9)21-8-20-12/h1-6H,7-8H2,(H,18,19)
  • Key:NMKJFZCBCIUYHI-UHFFFAOYSA-N

Alda-1 is an organic compound that enhances the enzymatic activity of human ALDH2. Alda-1 has been proposed as a potential treatment for the alcohol flush reaction experienced by people with genetically deficient ALDH2.

Mechanism of action

Ethanol is metabolized to acetaldehyde in people, which is then metabolized to acetic acid primarily by ALDH2. People have various ALDH2 alleles. ALDH2*1 is a common allele (wild type), but about 40% of people of East Asian ethnicity have one or two copies of the dominant ALDH2*2 instead, which causes ALDH2 deficiency. If deficient people drink ethanol, they suffer from alcohol flush reaction due to acetaldehyde accumulation.

Four Alda-1 molecules bind to each monomer of ALDH2 tetramer. This enhances NAD binding to ALDH2. NAD is required by ALDH2 for its enzymatic activity, which is why Alda-1 increases ALDH2 activity by 2.1 fold if ALDH2 is coded by ALDH2*1 and by 11 fold if it is coded ALDH2*2.

History

Chen et al. first reported Alda-1 in 2008. Alda-1 is the first known aldehyde dehydrogenase activator.

References

  1. ^ Ma X, Luo Q, Zhu H, Liu X, Dong Z, Zhang K, et al. (May 2018). "Aldehyde dehydrogenase 2 activation ameliorates CCl4 -induced chronic liver fibrosis in mice by up-regulating Nrf2/HO-1 antioxidant pathway". Journal of Cellular and Molecular Medicine. 22 (8): 3965–3978. doi:10.1111/jcmm.13677. PMC 6050510. PMID 29799157.
  2. ^ Chen CH, Budas GR, Churchill EN, Disatnik MH, Hurley TD, Mochly-Rosen D (September 2008). "Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart". Science. 321 (5895): 1493–5. Bibcode:2008Sci...321.1493C. doi:10.1126/science.1158554. PMC 2741612. PMID 18787169.
  3. ^ Mittal M, Bhagwati S, Siddiqi MI, Chattopadhyay N (November 2020). "A critical assessment of the potential of pharmacological modulation of aldehyde dehydrogenases to treat the diseases of bone loss". European Journal of Pharmacology. 886: 173541. doi:10.1016/j.ejphar.2020.173541. PMID 32896553. S2CID 221540241.
  4. Chen CH, Ferreira JC, Gross ER, Mochly-Rosen D (January 2014). "Targeting aldehyde dehydrogenase 2: new therapeutic opportunities". Physiological Reviews. 94 (1): 1–34. doi:10.1152/physrev.00017.2013. PMC 3929114. PMID 24382882.
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