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In this Review, Weber and Sullivan discuss the different types of immune-related adverse events associated with checkpoint inhibitors and how their treatment may shed light on their mechanisms and possible strategies and targets for prophylactic and therapeutic interventions to mitigate them.
Targeted protein degradation by proteolysis-targeting chimeras (PROTACs) is attracting substantial interest as a therapeutic modality that could circumvent some limitations of traditional small-molecule drugs. This article presents a systematic approach to assessing the PROTAC tractability (PROTACtability) of protein targets, which could support decision-making on whether a particular target may be amenable to modulation using a PROTAC.
As small activating RNAs gear up to enter phase II testing, other noncoding RNAs that upregulate gene expression are also progressing towards the clinic. But it’s early days for a complex field.
Numerous kidney diseases are characterized by a breakdown of the glomerular filtration barrier, which forms the interface between the blood and urine. In this Review, Daehn and Duffield discuss strategies to target components of this barrier, focusing on mechanisms to control mitochondrial function and the actin–myosin machinery, to improve kidney function in individuals with kidney diseases.
Luisa Salter-Cid, the Chief Scientific Officer of Pioneering Medicines, will build a portfolio of programmes by tapping technologies on offer at dozens of companies founded by venture capital firm Flagship.
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.
Research on sex differences in central nervous system disorders has developed substantially in recent years. Here, we discuss selected examples and the implications for drug development.
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.