The rise and rise of protein degradation: Opportunities and challenges ahead

Ian Churcher and colleagues, Amphista Therapeutics Ltd,

Drug Discovery Today 20 August 2021,

Standard E3 ligase design DrugDiscovery2021

Targeted protein degradation(TBD) has been one of the emerging approaches of the early 21st century particularly as unlike downregulation approaches which have the same conceptual advantage of reducing the amount of protein target present, there is the opportunity to operate a more “platform” approach.  This excellent review covers the strengths and weaknesses of different TPD approaches such as CRBN PROTACs, VHL PROTACs, IAP PROTACs, Molecular glues, AUTACs and LYTACs.  It also discusses the continuing challenges and possibilities in generating TPD agents  with oral bioavailability and even CNS exposure.