Aldehyde oxidase; new approaches to old problems

Abstract

1. Despite expanding knowledge on the structure and reactivity of human aldehyde oxidase (hAOX1) many drugs enter human studies only to be removed from further clinical trials due to aldehyde oxidase (AOX)-catalysed metabolism.

2. In addition to oxidation of numerous N-heterocycles and aldehydes, hAOX1 is also important in amide hydrolysis and reductive reactions.

3. This article reviews the evidence for hAOX1 polymorphism and other genetic factors which affect hAOX1 expression and which may lead to attenuated drug metabolism.

4. Difficulties in the selection of appropriate in silico and in vitro models for predicting hAOX1 metabolism are considered in the context of its wide substrate specificity.

Keywords:

• Aldehyde oxidase
• aldehydes
• genetic polymorphism
• hydrolysis
• N-heterocycles
• oxidation
• predictive models
• reduction

Disclosure statement

No potential conflict of interest was reported by the author.