Alda-1

Alda-1 is an organic compound that enhances the enzymatic activity of human ALDH2.^[1] Alda-1 has been proposed as a potential treatment for the alcohol flush reaction experienced by people with genetically deficient ALDH2.^[2]

Alda-1

Identifiers
IUPAC name N-(1,3-Benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide
CAS Number	349438-38-6
PubChem CID	831629
ChemSpider	726276
ChEBI	CHEBI:94988
ChEMBL	ChEMBL465952
CompTox Dashboard (EPA)	DTXSID801324445
Chemical and physical data
Formula	C15H11Cl2NO3
Molar mass	324.16 g·mol−1
3D model (JSmol)	Interactive image
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

Mechanism of action

Ethanol is metabolized to acetaldehyde in people, which is then metabolized to acetic acid primarily by ALDH2.^[1] 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.^[3]

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,^[4] 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.^[2]

History

Chen et al. first reported Alda-1 in 2008.^[2][1] Alda-1 is the first known aldehyde dehydrogenase activator.^[3]