Work

Chasing molecular glue degraders: screening approaches

Year: 2022

Type: review

Abstract: proteolysis-targeting chimeras - PROTACs) overcome some limitations of traditional occupancy-based therapeutics. Here, we provide an overview of the "molecular glue" concept, with a special focus on natural and synthetic inducers of proximity to E3s. We then briefly highlight the serendipitous discoveries of some clinical and preclinical molecular glue degraders, and discuss the first examples of intentional discoveries. Specifically, we outline the different screening strategies reported in this rapidly evolving arena and our thoughts on future perspectives. By mastering the ability to influence PPIs, molecular glue degraders can induce the degradation of unligandable proteins, thus providing an exciting path forward to broaden the targetable proteome.

Source: Chemical Society Reviews

DOI: 10.1039/d2cs00197g

Authors: Ana Domostegui, Luis Nieto-Barrado, Carles Perez-Lopez, Cristina Mayor-Ruiz

Institutions: Institute for Research in Biomedicine, Barcelona Institute of Science and Technology

Language: English

Topic: Protein Degradation and Inhibitors

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: Institute for Research in Biomedicine, Ministerio de Ciencia e Innovación, HORIZON EUROPE European Research Council