Targeted protein degradation in vivo with Proteolysis Targeting Chimeras: Current status and future considerations

Publication date: Available online 23 March 2019Source: Drug Discovery Today: TechnologiesAuthor(s): Gillian F. Watt, Paul Scott-Stevens, Lu GaohuaProteolysis Targeting Chimeras (PROTACs) are a rapidly expanding new therapeutic modality inducing selective protein degradation and offering the potential of a differentiated pharmacological profile across multiple therapeutic areas. As the repertoire of protein targets and E3 ligases available for incorporation into PROTACs continues to grow, understanding the drug- and system-dependent parameters for PROTACs will be critical for achieving tissue/cell specific pharmacology. The review discusses the current knowledge and future direction of in vivo PROTAC study evaluation. The importance of establishing the quantitative relationship between loss of protein target and biological function in vivo, coupled with building mechanistic PK/PD and ultimately PBPK/PD models, is emphasised with the aim to aid translation from preclinical to clinical space.Graphical abstract
Source: Drug Discovery Today: Technologies - Category: Drugs & Pharmacology Source Type: research