2. Academic Validation
  3. Molecular Glues for Targeted Protein Degradation: From Serendipity to Rational Discovery

Molecular Glues for Targeted Protein Degradation: From Serendipity to Rational Discovery

  • J Med Chem. 2021 Aug 12;64(15):10606-10620. doi: 10.1021/acs.jmedchem.1c00895.
Guoqiang Dong 1,  Yu Ding 2,  Shipeng He 3,  Chunquan Sheng 1
Affiliations

Affiliations

  • 1 School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
  • 2 Neurology Department at Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China.
  • 3 Institute of Translational Medicine, Shanghai University, 99 Shangda Road, Shanghai 200444, China.
PMID: 34319094 DOI: 10.1021/acs.jmedchem.1c00895
Abstract

Targeted protein degradation is a promising area in the discovery and development of innovative therapeutics. Molecular Glues mediate proximity-induced protein degradation and have intrinsic advantages over heterobifunctional proteolysis-targeting chimeras, including unprecedented mechanisms, distinct biological activities, and favorable physicochemical properties. Classical molecular glue degraders have been identified serendipitously, but rational discovery and design strategies are emerging rapidly. In this review, we aim to highlight the recent advances in Molecular Glues for targeted protein degradation and discuss the challenges in developing Molecular Glues into therapeutic agents. In particular, discovery strategies, action mechanisms, and representative case studies will be addressed.

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