Protein Degradation with New Chemical Modalities
Chapter 9: An Efficient Approach Toward Drugging Undruggable Targets
Published:07 Oct 2020
K. Gamo, N. Kitamoto, M. T. Kanemaki, and Y. Tominari, in Protein Degradation with New Chemical Modalities, ed. H. Weinmann and C. Crews, The Royal Society of Chemistry, 2020, ch. 9, pp. 167-183.
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Targeted protein degradation (TPD) is under intensive focus with respect to the next-generation drugs to target currently undruggable proteins. Bivalent type degraders, known as proteolysis-targeting chimeras (PROTACs), are an attractive but challenging novel modality. As drug discovery for TPD involves time-consuming and costly processes, it is important to establish a platform for not only the identification and validation of the targets but also rapid and efficient drug discovery. Herein, two processes were proposed: (1) target validation by a ligand-induced genetic degradation system, especially the Auxin-Inducible Degron (AID) system and (2) degrader drug discovery by Rapid Protein Proteolysis Inducer Discovery System (RaPPIDSTM). Moreover, a strategy was developed for the discovery of TPD drugs against novel target proteins.