Transforming targeted cancer therapy with PROTACs:  A forward-looking perspective

William Farnaby; Manfred Koegl; Darryl B. McConnell; Alessio Ciulli

doi:10.1016/j.coph.2021.02.009

Transforming targeted cancer therapy with PROTACs: A forward-looking perspective

William Farnaby (Lead / Corresponding author)
, Manfred Koegl (Lead / Corresponding author)
, Darryl B. McConnell
, Alessio Ciulli

Biological Chemistry and Drug Discovery

Research output: Contribution to journal › Review article › peer-review

44 Citations (Scopus)

381 Downloads (Pure)

Abstract

Small-molecule targeted protein degraders have in recent years made a great impact on the strategies of many industry and academic cancer research endeavours. We seek here to provide a concise perspective on the opportunities and challenges that lie ahead for bifunctional degrader molecules, so-called ‘Proteolysis Targeting Chimeras (PROTACs),’ in the context of cancer therapy. We highlight high-profile studies that support the potential for PROTAC approaches to broaden drug target scope, address drug resistance, enhance target selectivity and provide tissue specificity, but also assess where the modality is yet to fully deliver in these contexts. Future opportunities presented by the unique bifunctional nature of these molecules are also discussed.

Original language	English
Pages (from-to)	175-183
Number of pages	9
Journal	Current Opinion in Pharmacology
Volume	57
Early online date	30 Mar 2021
DOIs	https://doi.org/10.1016/j.coph.2021.02.009
Publication status	Published - Apr 2021

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Targeted protein degradation
PROTACs
Cancer
Bifunctional molecules
Drug discovery
Target selectivity
Drug resistance

ASJC Scopus subject areas

Drug Discovery
Pharmacology

Access to Document

10.1016/j.coph.2021.02.009Licence: Elsevier User Licence

Author Accepted ManuscriptAccepted author manuscript, 304 KBLicence: CC BY-NC-ND

Cite this

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title = "Transforming targeted cancer therapy with PROTACs: A forward-looking perspective",

abstract = "Small-molecule targeted protein degraders have in recent years made a great impact on the strategies of many industry and academic cancer research endeavours. We seek here to provide a concise perspective on the opportunities and challenges that lie ahead for bifunctional degrader molecules, so-called {\textquoteleft}Proteolysis Targeting Chimeras (PROTACs),{\textquoteright} in the context of cancer therapy. We highlight high-profile studies that support the potential for PROTAC approaches to broaden drug target scope, address drug resistance, enhance target selectivity and provide tissue specificity, but also assess where the modality is yet to fully deliver in these contexts. Future opportunities presented by the unique bifunctional nature of these molecules are also discussed.",

keywords = "Targeted protein degradation, PROTACs, Cancer, Bifunctional molecules, Drug discovery, Target selectivity, Drug resistance",

author = "William Farnaby and Manfred Koegl and McConnell, \{Darryl B.\} and Alessio Ciulli",

year = "2021",

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language = "English",

volume = "57",

pages = "175--183",

journal = "Current Opinion in Pharmacology",

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T2 - A forward-looking perspective

AU - Farnaby, William

AU - Koegl, Manfred

AU - McConnell, Darryl B.

AU - Ciulli, Alessio

PY - 2021/4

Y1 - 2021/4

N2 - Small-molecule targeted protein degraders have in recent years made a great impact on the strategies of many industry and academic cancer research endeavours. We seek here to provide a concise perspective on the opportunities and challenges that lie ahead for bifunctional degrader molecules, so-called ‘Proteolysis Targeting Chimeras (PROTACs),’ in the context of cancer therapy. We highlight high-profile studies that support the potential for PROTAC approaches to broaden drug target scope, address drug resistance, enhance target selectivity and provide tissue specificity, but also assess where the modality is yet to fully deliver in these contexts. Future opportunities presented by the unique bifunctional nature of these molecules are also discussed.

AB - Small-molecule targeted protein degraders have in recent years made a great impact on the strategies of many industry and academic cancer research endeavours. We seek here to provide a concise perspective on the opportunities and challenges that lie ahead for bifunctional degrader molecules, so-called ‘Proteolysis Targeting Chimeras (PROTACs),’ in the context of cancer therapy. We highlight high-profile studies that support the potential for PROTAC approaches to broaden drug target scope, address drug resistance, enhance target selectivity and provide tissue specificity, but also assess where the modality is yet to fully deliver in these contexts. Future opportunities presented by the unique bifunctional nature of these molecules are also discussed.

KW - Targeted protein degradation

KW - PROTACs

KW - Cancer

KW - Bifunctional molecules

KW - Drug discovery

KW - Target selectivity

KW - Drug resistance

UR - https://www.scopus.com/pages/publications/85103404664

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DO - 10.1016/j.coph.2021.02.009

M3 - Review article

C2 - 33799000

SN - 1471-4892

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SP - 175

EP - 183

JO - Current Opinion in Pharmacology

JF - Current Opinion in Pharmacology

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