An overview of aldehyde oxidase: an enzyme of emerging importance in novel drug discovery
| Autor: | Mohammad-Reza Rashidi, Somaieh Soltani |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Drug media_common.quotation_subject Computational biology Biology 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Animal model Species Specificity AOX activity Biological variation Drug Discovery Animals Humans Computer Simulation Aldehyde oxidase media_common chemistry.chemical_classification Drug discovery Aldehyde Oxidase 030104 developmental biology Enzyme Pharmaceutical Preparations chemistry Biochemistry Drug Design Computer-Aided Design Metabolic activity |
| Zdroj: | Expert Opinion on Drug Discovery. 12:305-316 |
| ISSN: | 1746-045X 1746-0441 |
| DOI: | 10.1080/17460441.2017.1284198 |
| Popis: | Given the rising trend in medicinal chemistry strategy to reduce cytochrome P450-dependent metabolism, aldehyde oxidase (AOX) has recently gained increased attention in drug discovery programs and the number of drug candidates that are metabolized by AOX is steadily growing. Areas covered: Despite the emerging importance of AOX in drug discovery, there are certain major recognized problems associated with AOX-mediated metabolism of drugs. Intra- and inter-species variations in AOX activity, the lack of reliable and predictive animal models using the common experimental animals, and failure in the predictions of in vivo metabolic activity of AOX using traditional in vitro methods are among these issues that are covered in this article. A comprehensive review of computational human AOX (hAOX) related studies are also provided. Expert opinion: Following the recent progress in the stem cell field, the authors recommend the application of organoids technology as an effective tool to solve the fundamental problems associated with the evaluation of AOX in drug discovery. The recent success in resolving the hAOX crystal structure can too be another valuable data source for the study of AOX-catalyzed metabolism of new drug candidates, using computer-aided drug discovery methods. |
| Databáze: | OpenAIRE |
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