PROTAC Degraders: Mechanism, recent advances, and future challenges

Alessio Ciulli; Oliver Hsia

doi:10.1002/9781119774198.ch9

PROTAC Degraders: Mechanism, recent advances, and future challenges

Alessio Ciulli, Oliver Hsia

Biological Chemistry and Drug Discovery

Research output: Chapter in Book/Report/Conference proceeding › Chapter (peer-reviewed) › peer-review

3 Citations (Scopus)

Abstract

Proteolysis-targeting chimeras (PROTACs) are an emerging modality in targeted protein degradation and represent a key class of drugs that may yield significant benefit in the treatment of a wide range of diseases. In recent years, the field has witnessed a significant rise not only in the number of PROTAC molecules being developed and that have reached clinical settings but also in technologies and applications of degraders and beyond. This chapter covers some of the recent advances in the PROTAC space, from novel E3 ligases beyond the most-commonly used CRBN and VHL that have been hijacked, to next-generation degraders such as trivalent PROTACs and covalent PROTACs. We also highlight some of the emerging drug-resistance mechanisms that have been described particularly for VHL and CRBN-recruiting degraders.

Original language	English
Title of host publication	Protein Homeostasis in Drug Discovery
Subtitle of host publication	A Chemical Biology Perspective
Editors	Milka Kostic, Lyn H. Jones
Place of Publication	Hoboken, NJ
Publisher	Wiley
Chapter	9
Pages	317-356
Number of pages	40
ISBN (Electronic)	9781119774198
ISBN (Print)	9781119774129
DOIs	https://doi.org/10.1002/9781119774198.ch9
Publication status	Published - 18 Nov 2022

Keywords

Cancer
Drug resistance
Proteolysis-targeting chimeras
Targeted protein degradation
Ubiquitination

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Medicine
Pharmacology, Toxicology and Pharmaceutics(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/9781119774198.ch9

Cite this

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title = "PROTAC Degraders: Mechanism, recent advances, and future challenges",

abstract = "Proteolysis-targeting chimeras (PROTACs) are an emerging modality in targeted protein degradation and represent a key class of drugs that may yield significant benefit in the treatment of a wide range of diseases. In recent years, the field has witnessed a significant rise not only in the number of PROTAC molecules being developed and that have reached clinical settings but also in technologies and applications of degraders and beyond. This chapter covers some of the recent advances in the PROTAC space, from novel E3 ligases beyond the most-commonly used CRBN and VHL that have been hijacked, to next-generation degraders such as trivalent PROTACs and covalent PROTACs. We also highlight some of the emerging drug-resistance mechanisms that have been described particularly for VHL and CRBN-recruiting degraders.",

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AU - Ciulli, Alessio

AU - Hsia, Oliver

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Y1 - 2022/11/18

N2 - Proteolysis-targeting chimeras (PROTACs) are an emerging modality in targeted protein degradation and represent a key class of drugs that may yield significant benefit in the treatment of a wide range of diseases. In recent years, the field has witnessed a significant rise not only in the number of PROTAC molecules being developed and that have reached clinical settings but also in technologies and applications of degraders and beyond. This chapter covers some of the recent advances in the PROTAC space, from novel E3 ligases beyond the most-commonly used CRBN and VHL that have been hijacked, to next-generation degraders such as trivalent PROTACs and covalent PROTACs. We also highlight some of the emerging drug-resistance mechanisms that have been described particularly for VHL and CRBN-recruiting degraders.

AB - Proteolysis-targeting chimeras (PROTACs) are an emerging modality in targeted protein degradation and represent a key class of drugs that may yield significant benefit in the treatment of a wide range of diseases. In recent years, the field has witnessed a significant rise not only in the number of PROTAC molecules being developed and that have reached clinical settings but also in technologies and applications of degraders and beyond. This chapter covers some of the recent advances in the PROTAC space, from novel E3 ligases beyond the most-commonly used CRBN and VHL that have been hijacked, to next-generation degraders such as trivalent PROTACs and covalent PROTACs. We also highlight some of the emerging drug-resistance mechanisms that have been described particularly for VHL and CRBN-recruiting degraders.

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KW - Drug resistance

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BT - Protein Homeostasis in Drug Discovery

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PROTAC Degraders: Mechanism, recent advances, and future challenges

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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