2. Academic Validation
  3. PROTACs: An Emerging Therapeutic Modality in Precision Medicine

PROTACs: An Emerging Therapeutic Modality in Precision Medicine

  • Cell Chem Biol. 2020 Aug 20;27(8):998-1014. doi: 10.1016/j.chembiol.2020.07.020.
Dhanusha A Nalawansha 1,  Craig M Crews 2
Affiliations

Affiliations

  • 1 Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.
  • 2 Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA; Department of Chemistry, Yale University, New Haven, CT 06511, USA; Department of Pharmacology, Yale University, New Haven, CT 06511, USA. Electronic address: [email protected].
PMID: 32795419 DOI: 10.1016/j.chembiol.2020.07.020
Abstract

Targeted protein degradation (TPD) has emerged as an exciting new era in chemical biology and drug discovery. PROteolysis TArgeting Chimera (PROTAC) technology targets cellular proteins for degradation by co-opting the ubiquitin-proteasome system. Over the last 5 years, numerous studies have expanded our understanding of the unique mode of action and advantages of PROTACs, which has in turn spurred interest in both academia and industry to explore PROTACs as a novel therapeutic strategy. In this review, we first highlight the key advantages of PROTACs and then discuss the spatiotemporal regulation of protein degradation. Next, we explore current chemically tractable E3 Ligases focusing on expanding the existing repertoire with novel E3 Ligases to uncover the full potential of TPD. Collectively, these studies are guiding the development of the PROTAC technology as it emerges as a new modality in precision medicine.

Keywords

E3 ligase; PROTACs; PhotoPROTACs; covalent ligands; proteasome; targeted protein degradation.

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