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| ChEMBL | |
| CompTox Dashboard ( EPA) | |
| Chemical and physical data | |
| Formula | C15H11Cl2NO3 |
| Molar mass | 324.16 g·mol−1 |
| 3D model ( JSmol) | |
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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]
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]
References
- ^ a b c 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.
- ^ a b c 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.
- ^ a b 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.
- ^ 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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| Identifiers | |
|---|---|
| |
| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard ( EPA) | |
| Chemical and physical data | |
| Formula | C15H11Cl2NO3 |
| Molar mass | 324.16 g·mol−1 |
| 3D model ( JSmol) | |
| |
| |
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]
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]
References
- ^ a b c 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.
- ^ a b c 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.
- ^ a b 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.
- ^ 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.