Literature DB >> 33799000

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

William Farnaby1, Manfred Koegl2, Darryl B McConnell3, Alessio Ciulli4.   

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.
Copyright © 2021 Elsevier Ltd. All rights reserved.

Entities:  

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

Year:  2021        PMID: 33799000     DOI: 10.1016/j.coph.2021.02.009

Source DB:  PubMed          Journal:  Curr Opin Pharmacol        ISSN: 1471-4892            Impact factor:   5.547


  13 in total

1.  Identification of ligand linkage vectors for the development of p300/CBP degraders.

Authors:  Duncan K Brownsey; Ben C Rowley; Evgueni Gorobets; Koichiro Mihara; Ranjan Maity; James W Papatzimas; Benjamin S Gelfand; Morley D Hollenberg; Nizar J Bahlis; Darren J Derksen
Journal:  RSC Med Chem       Date:  2022-04-14

Review 2.  Major Advances in Emerging Degrader Technologies.

Authors:  Hang Luo; Li Wu; Yujian He; Chong Qin; Xinjing Tang
Journal:  Front Cell Dev Biol       Date:  2022-06-22

3.  Deubiquitinase-targeting chimeras for targeted protein stabilization.

Authors:  Nathaniel J Henning; Lydia Boike; Jessica N Spradlin; Carl C Ward; Gang Liu; Erika Zhang; Bridget P Belcher; Scott M Brittain; Matthew J Hesse; Dustin Dovala; Lynn M McGregor; Rachel Valdez Misiolek; Lindsey W Plasschaert; David J Rowlands; Feng Wang; Andreas O Frank; Daniel Fuller; Abigail R Estes; Katelyn L Randal; Anoohya Panidapu; Jeffrey M McKenna; John A Tallarico; Markus Schirle; Daniel K Nomura
Journal:  Nat Chem Biol       Date:  2022-02-24       Impact factor: 16.174

4.  Novel SMARCA Degraders for Treating Cancer.

Authors:  Ram W Sabnis
Journal:  ACS Med Chem Lett       Date:  2022-08-30       Impact factor: 4.632

5.  Bifunctional Compounds as SMARCA2 Degraders for Treating Cancer.

Authors:  Ram W Sabnis
Journal:  ACS Med Chem Lett       Date:  2021-12-10       Impact factor: 4.345

Review 6.  Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants.

Authors:  Marco H Hofmann; Daniel Gerlach; Sandra Misale; Mark Petronczki; Norbert Kraut
Journal:  Cancer Discov       Date:  2022-04-01       Impact factor: 38.272

7.  Expression and purification of functional recombinant CUL2•RBX1 from E. coli.

Authors:  Stephanie Diaz; Lihong Li; Kankan Wang; Xing Liu
Journal:  Sci Rep       Date:  2021-05-27       Impact factor: 4.379

Review 8.  PROTAC targeted protein degraders: the past is prologue.

Authors:  Miklós Békés; David R Langley; Craig M Crews
Journal:  Nat Rev Drug Discov       Date:  2022-01-18       Impact factor: 112.288

Review 9.  Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases.

Authors:  Stephanie Diaz; Kankan Wang; Benita Sjögren; Xing Liu
Journal:  Biomolecules       Date:  2022-03-08

Review 10.  Degraders: The Ultimate Weapon Against Amplified Driver Kinases in Cancer.

Authors:  Pedro Torres-Ayuso; John Brognard
Journal:  Mol Pharmacol       Date:  2022-02-03       Impact factor: 4.054

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