Volume 20 Issue 9, September 2021

Despite a regulatory setback for Provention Bio’s diabetes prevention candidate teplizumab, hopes remain high for T cell-regulating therapies in autoimmune indications including multiple sclerosis, systemic lupus erythematosus and coeliac disease.

Transcription factors have key roles in a variety of diseases, but they have been traditionally considered ‘undruggable’ by small-molecule ligands. Here, Henley and Koehler provide an overview of current understanding of transcription factor-mediated gene regulation, assess successful and emerging strategies to modulate transcription factor activity and address the associated challenges.

Although oxidative stress is associated with a broad range of diseases, therapeutic antioxidant approaches have so far been disappointing. Here, Forman and Zhang review the roles of oxidative stress and redox signalling in disease, assess antioxidant therapeutic strategies and highlight key limitations that have challenged their clinical application.

A substantial proportion of drug targets are embedded in a cellular membrane, and growing evidence shows that some small molecules access their target via a membrane pathway. Here, Payandeh and Volgraf consider the importance of drug binding at the protein–phospholipid interface, and suggest strategies to harness these concepts for improved drug design.