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- W3198565585 abstract "Undruggable targets refer to clinically meaningful therapeutic targets that are 'difficult to drug' or 'yet to be drugged' via traditional approaches. Featuring characteristics of lacking defined ligand-binding pockets, non-catalytic protein-protein interaction functional modes and less-investigated 3D structures, these undruggable targets have been targeted with novel therapeutic entities developed with the progress of unconventional drug discovery approaches, such as targeted degradation molecules and display technologies.This review first presents the concept of 'undruggable' exemplified by RAS and other targets. Next, detailed strategies are illustrated in two aspects: innovation of therapeutic entities and development of unconventional drug discovery technologies. Finally, case studies covering typical undruggable targets (Bcl-2, p53, and RAS) are depicted to further demonstrate the feasibility of the strategies and entities above.Targeting the undruggable expands the scope of therapeutically reachable targets. Consequently, it represents the drug discovery frontier. Biomedical studies are capable of dissecting disease mechanisms, thus broadening the list of undruggable targets. Encouraged by the recent approval of the KRAS inhibitor Sotorasib, we believe that merging multiple discovery approaches and exploiting various novel therapeutic entities would pave the way for dealing with more 'undruggable' targets in the future." @default.
- W3198565585 created "2021-09-13" @default.
- W3198565585 creator A5026949730 @default.
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- W3198565585 creator A5031383697 @default.
- W3198565585 creator A5058892609 @default.
- W3198565585 creator A5090927636 @default.
- W3198565585 date "2021-08-30" @default.
- W3198565585 modified "2023-10-01" @default.
- W3198565585 title "Strategies for targeting undruggable targets" @default.
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