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Published on: November 9, 2020
Bioorthogonal Chemistry: An Emerging Strategy for Targeted Protein Degradation
Pijun Zhou1, Junda Li1, Jinyi Xu1
1Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
Abstract:
Targeted protein degradation (TPD) technologies represent a promising strategy to overcome drug resistance associated with traditional small-molecule inhibitors (SMIs) while targeting traditionally considered nondruggable targets. However, the frequent noncompliance of TPD agents with Lipinski's "Rule of Five" poses significant druggability challenges. Off-target toxicity and the "hook effect" further limit TPD applications. With the development of bioorthogonal chemistry, self-assembly TPD agents and TPD agent prodrugs based on bioorthogonal chemistry offer a viable solution to address these issues. This review summarizes recent advances in integrating bioorthogonal chemistry with TPD technologies, specifically highlighting its role in improving conventional TPD agents drawbacks.
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