Design, synthesis, and ex vivo evaluation of a selective inhibitor for retinaldehyde dehydrogenase enzymes.
Bioorg Med Chem
; 26(22): 5766-5779, 2018 12 01.
Article
in En
| MEDLINE
| ID: mdl-30409702
ABSTRACT
The retinaldehyde dehydrogenase (RALDH) enzymes, RALDH1, RALDH2, and RALDH3, catalyze the irreversible oxidation of retinaldehyde to all-trans-retinoic acid (ATRA). Despite the importance of the RALDH enzymes in embryonic development, postnatal growth and differentiation, and in several disease states, there are no commercially available inhibitors that specifically target these isozymes. We report here the development and characterization of a small molecule inhibitor dichloro-all-trans-retinone (DAR) (Summers et al., 2017) that is an irreversible inhibitor of RALDH1, 2, and 3 that effectively inhibits RALDH1, 2, and 3 in the nanomolar range but has no inhibitory activity against mitochondrial ALDH2. These results provide support for the development of DAR as a specific ATRA synthesis inhibitor for a variety of experimental and clinical applications.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Design
/
Aldehyde Dehydrogenase
/
Aldehyde Oxidoreductases
/
Enzyme Inhibitors
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Retinal Dehydrogenase
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Bioorg Med Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2018
Type:
Article
Affiliation country:
United States