Aldehyde oxidase at the crossroad of metabolism and preclinical screening.
Drug Metab Rev
; 51(4): 428-452, 2019 11.
Article
in En
| MEDLINE
| ID: mdl-31549868
ABSTRACT
Human AOX1 is a member of the mammalian aldehyde oxidase (AOX) family of enzymes and it is an emerging cytosolic enzyme involved in phase I drug-metabolism, bio-transforming a number of therapeutic agents and xenobiotics. The current trend in drug-development is to design molecules which are not recognized and inactivated by CYP450 monooxygenases, the main drug-metabolizing system, to generate novel therapeutic agents characterized by optimal pharmacokinetic and pharmacodynamic properties. Unfortunately, this has resulted in a substantial enrichment in molecules which are recognized and metabolized by AOXs. The observation has raised interest in the generation of tools capable of predicting AOX-dependent drug-metabolism of novel molecules during the early phases of drug development. Such tools are likely to reduce the number of failures occurring at the clinical and late phase of the drug development process. The current review describes different in silico, in vitro and in vivo methods for the prediction of AOX metabolizing ability and focuses on the existing drawbacks and challenges associated with these approaches.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pharmaceutical Preparations
/
Aldehyde Oxidase
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Drug Metab Rev
Year:
2019
Document type:
Article
Affiliation country:
Irán