ABSTRACT
Introduction: In recent years, development of novel bioactive small molecules targeting autophagy has been implicated for autophagy-related disease treatment. Screening new small molecules regulating autophagy allows for the discovery of novel autophagy machinery and therapeutic agents.
Areas covered: Two major screening methods for novel autophagy modulators are introduced in this review, namely target based screening and phenotype based screening. With increasing attention focused on chemical compound libraries, coupled with the development of new assay systems, this review attempts to provide an efficient strategy to explore autophagy biology and discover small molecules for the treatment of autophagy-related diseases.
Expert opinion: Adopting an appropriate autophagy screening strategy is important for developing small molecules capable of treating neurodegenerative diseases and cancers. Phenotype based screening and target based screening were both used for developing effective small molecules. However, each of these methods has many pros and cons. An efficient approach is suggested to screen for novel lead compounds targeting autophagy, which could provide new hits with better efficiency and rapidity.
Article highlights
Autophagy is induced to maintain cellular homeostasis in response to various pathological invasion, nutrient starvation, and aggregation of cytosolic components leading to human pathological conditions. Recently, many reports have highlighted chemical compounds modulating autophagy.
Many chemical libraries, which include synthetic, natural, and clinical products, have been used to discover autophagy-modulating ‘hit’ compounds in screening systems.
There are two such methods, phenotype based screening and target based screening, for developing effective drugs targeting autophagy. Phenotype screening has been mainly used for cell based screening system, and target based screening has been used for biochemical and biophysical methods.
The pros and cons of these methods must be carefully weighed up for developing better methods of identifying new small molecules targeting autophagy. Mutual complementation of these methods can compensate the pros and cons of each method and improve the current screening systems.
Newly discovered compounds that modulate autophagy through this platform can be applied as chemical tools for discovering key players of autophagy as well as targeting autophagy related diseases.
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Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.