Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, UK.
Boehringer Ingelheim RCV GmbH & Co KG, Dr. Boehringer Gasse 5-11, A-1121, Vienna, Austria.
Curr Opin Pharmacol. 2021 Apr;57:175-183. doi: 10.1016/j.coph.2021.02.009. Epub 2021 Mar 30.
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.
近年来,小分子靶向蛋白降解剂在许多工业界和学术界的癌症研究工作中产生了重大影响。我们在此旨在简要探讨双功能降解剂分子(即“蛋白水解靶向嵌合体(PROTACs)”)在癌症治疗方面所面临的机遇和挑战。我们强调了一些支持 PROTAC 方法在扩大药物靶标范围、解决耐药性、提高靶标选择性和提供组织特异性方面潜力的重要研究,但也评估了在这些情况下该方法尚未完全发挥作用的地方。还讨论了这些分子独特的双功能性质所带来的未来机遇。