Aldehyde oxidase mediated drug metabolism: an underpredicted obstacle in drug discovery and development

Gajula, Siva Nageswara Rao; Nathani, Tanaaz Navin; Patil, Rashmi Madhukar; Talari, Sasikala; Sonti, Rajesh

doi:10.1080/03602532.2022.2144879

Cited by 12 publications

(4 citation statements)

References 85 publications

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“…The liver is a vital organ involved in various metabolic processes, drug metabolism, and detoxification [ 89 , 90 ]. Therefore, liver-specific nanozymes hold great potential for applications in liver-targeted drug delivery, liver disease diagnosis, and therapeutic interventions.…”

Section: Rational Design Strategiesmentioning

confidence: 99%

Nanozyme as a rising star for metabolic disease management

Wang,

He,

Huang

et al. 2024

J Nanobiotechnol

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Nanozyme, characterized by outstanding and inherent enzyme-mimicking properties, have emerged as highly promising alternatives to natural enzymes owning to their exceptional attributes such as regulation of oxidative stress, convenient storage, adjustable catalytic activities, remarkable stability, and effortless scalability for large-scale production. Given the potent regulatory function of nanozymes on oxidative stress and coupled with the fact that reactive oxygen species (ROS) play a vital role in the occurrence and exacerbation of metabolic diseases, nanozyme offer a unique perspective for therapy through multifunctional activities, achieving essential results in the treatment of metabolic diseases by directly scavenging excess ROS or regulating pathologically related molecules. The rational design strategies, nanozyme-enabled therapeutic mechanisms at the cellular level, and the therapies of nanozyme for several typical metabolic diseases and underlying mechanisms are discussed, mainly including obesity, diabetes, cardiovascular disease, diabetic wound healing, and others. Finally, the pharmacokinetics, safety analysis, challenges, and outlooks for the application of nanozyme are also presented. This review will provide some instructive perspectives on nanozyme and promote the development of enzyme-mimicking strategies in metabolic disease therapy. Graphical Abstract

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Section: Rational Design Strategiesmentioning

confidence: 99%

Nanozyme as a rising star for metabolic disease management

Wang,

He,

Huang

et al. 2024

J Nanobiotechnol

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“…Although the majority of the attention in drug metabolism studies has been paid to CYP, the other Phase I metabolism enzymes are being increasingly studied in recent years, including aldehyde oxidases (AOXs). AOXs are cytosolic non-NADPH dependent soluble molybdoflavo-enzymes belonging to the xanthine oxidase family [46]. They oxidize aldehydes to their corresponding carboxylic acids and hydroxylate N-heterocyclic compounds.…”

Section: Drug Metabolism Studiesmentioning

confidence: 99%

Atypical applications of transverse diffusion of laminar flow profiles methodology for in‐capillary reactions in capillary electrophoresis

Bržezická,

Kohútová,

Glatz

2024

J of Separation Science

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Capillary electrophoresis (CE) is a powerful separation technique offering quick and efficient analyses in various fields of bioanalytical chemistry. It is characterized by many well‐known advantages, but one, which is perhaps the most important for this application field, is somewhat overlooked. It is the possibility to perform chemical and biochemical reactions at the nL scale inside the separation capillary. There are two basic formats applicable for this purpose, heterogeneous and homogeneous. In the former, one reactant is immobilized onto a particle or monolithic support or directly on the capillary wall, and the other is injected. In the latter, the reactant mixing inside a capillary is based on electromigration or diffusion. One of the diffusion‐based methodologies, termed Transverse Diffusion of Laminar Flow Profiles, is the subject of this review. Since most studies utilizing in‐capillary reactions in CE focus on enzymes, which are being continuously and exhaustively reviewed, this review covers the atypical applications of this methodology, but still in the bioanalytical field. As can be seen from the demonstrated applications, they are not limited to reactions, but can also be utilized for other biochemical systems.

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“…Among these, the transformation of N -heterocycles to the corresponding oxo- N -heterocycles is the most concerning AOX-mediated metabolic reaction in drug discovery. It has contributed to the clinical failure of many novel agents, such as carbazeran, BIBX1382, FK3453, JNJ-38877605, and Lu AF09535 11 , 12 , 13 . These drugs are mainly kinase inhibitors, as their structures generally include nitrogen-containing heterocycles as important binding motifs, making them more likely to be liable to AOX-mediated metabolism 14 , 15 , 16 .…”

Section: Introductionmentioning

confidence: 99%