1. The rise of degrader drugs.
- Author
-
Teng, Mingxing and Gray, Nathanael S.
- Subjects
- *
DRUG discovery , *SMALL molecules , *MULTIPLE myeloma , *DRUG development , *PROTEOLYSIS , *IMATINIB , *HOMEOSTASIS - Abstract
The cancer genomics revolution has served up a plethora of promising and challenging targets for the drug discovery community. The field of targeted protein degradation (TPD) uses small molecules to reprogram the protein homeostasis system to destroy desired target proteins. In the last decade, remarkable progress has enabled the rational development of degraders for a large number of target proteins, with over 20 molecules targeting more than 12 proteins entering clinical development. While TPD has been fully credentialed by the prior development of immunomodulatory drug (IMiD) class for the treatment of multiple myeloma, the field is poised for a "Gleevec moment" in which robust clinical efficacy of a rationally developed novel degrader against a preselected target is firmly established. Here, we endeavor to provide a high-level evaluation of exciting developments in the field and comment on steps that may realize the full potential of this new therapeutic modality. [Display omitted] Teng et al. present a summary of recent progress in the rapidly evolving field of targeted protein degradation, with a particular emphasis on the opportunities and approaches for translation. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF