Frontiers in PROTACs

Gregory R. Hughes; Ashley P. Dudey; Andrew M. Hemmings; Andrew Chantry

doi:10.1016/j.drudis.2021.04.010

Frontiers in PROTACs

Gregory R. Hughes, Ashley P. Dudey, Andrew M. Hemmings, Andrew Chantry

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

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Abstract

Targeting protein–protein interactions (PPI) is a key focus in the development of new and emerging small-molecule therapeutics. Shallow interacting surfaces can render PPI targeting notoriously difficult. This leaves many therapeutically captivating targets ‘undruggable’. Despite these challenges, there has been extraordinary progress circumventing this issue by hijacking the ubiquitin proteasome system (UPS) to target selected substrates for destruction using target-based degradation (TBD) strategies, including bifunctional molecules known as proteolysis-targeting chimeras (PROTACs). In this review, we discuss some of the most recent innovative concepts emerging from PROTAC research and related technologies.

Original language	English
Pages (from-to)	2377-2383
Number of pages	7
Journal	Drug Discovery Today
Volume	26
Issue number	10
Early online date	17 Apr 2021
DOIs	https://doi.org/10.1016/j.drudis.2021.04.010
Publication status	Published - Oct 2021

Keywords

Drug discovery
PROTACs
Ubiquitin ligases

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10.1016/j.drudis.2021.04.010

Accepted_ManuscriptAccepted author manuscript, 450 KBLicence: CC BY-NC-ND

https://linkinghub.elsevier.com/retrieve/pii/S1359644621001963

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AU - Hughes, Gregory R.

AU - Dudey, Ashley P.

AU - Hemmings, Andrew M.

AU - Chantry, Andrew

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AB - Targeting protein–protein interactions (PPI) is a key focus in the development of new and emerging small-molecule therapeutics. Shallow interacting surfaces can render PPI targeting notoriously difficult. This leaves many therapeutically captivating targets ‘undruggable’. Despite these challenges, there has been extraordinary progress circumventing this issue by hijacking the ubiquitin proteasome system (UPS) to target selected substrates for destruction using target-based degradation (TBD) strategies, including bifunctional molecules known as proteolysis-targeting chimeras (PROTACs). In this review, we discuss some of the most recent innovative concepts emerging from PROTAC research and related technologies.

KW - Drug discovery

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KW - Ubiquitin ligases

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JO - Drug Discovery Today

JF - Drug Discovery Today

SN - 1359-6446

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Frontiers in PROTACs

Abstract

Keywords

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