Target validation articles from across Nature Portfolio

The National Institute of Neurological Disorders and Stroke (NINDS) held an open workshop on April 23 and 24, 2024 to evaluate the gap between the current understanding of Parkinson’s disease (PD) and the development of therapeutics for treating PD. Representatives from key stakeholder groups discussed strategies for leveraging research to bridge this gap. Sessions focused on PD heterogeneity, target validation, development of tools and resources to facilitate therapeutics development, biomarker discovery and use, similarities and differences with PD-adjacent neurodegenerative diseases, and best practices for accelerating the therapeutics development process. Here are some of the main takeaways from the workshop.

Chemically induced protein degradation is a powerful alternative to classical inhibition, but some proteins have deeply masked binding pockets that make the development of degrader molecules difficult. Here, the authors discover an alternate site on nuclear receptors that can be targeted by degraders.

In this work, Urem et al. characterize the mode of action as well as mechanism of reduced susceptibility related to a class of antimicrobials that is in development for the treatment of infections with Gram-positive pathogens.

The oxytocin/oxytocin receptor (OT/OTR) signalling system is a promising therapeutic target for socioemotional disorders, yet its clinical potential is limited by a lack of in vivo molecular tools. Here, the authors develop and validate [¹⁸F]dOTK⁸[SFB] as a PET radiotracer, demonstrating its specificity and potential for in vivo mapping OT/OTR biodistribution.

The National Institute of Neurological Disorders and Stroke (NINDS) held an open workshop on April 23 and 24, 2024 to evaluate the gap between the current understanding of Parkinson’s disease (PD) and the development of therapeutics for treating PD. Representatives from key stakeholder groups discussed strategies for leveraging research to bridge this gap. Sessions focused on PD heterogeneity, target validation, development of tools and resources to facilitate therapeutics development, biomarker discovery and use, similarities and differences with PD-adjacent neurodegenerative diseases, and best practices for accelerating the therapeutics development process. Here are some of the main takeaways from the workshop.

A new study combines massively parallel assays, transcriptomics and biophysical modeling to provide a framework for analyzing the effects of compounds that modulate pre-mRNA splicing. The results lend important insights into the mechanisms of drug action and facilitate the design of splicing therapies.

The recent design of mutation-selective KRAS inhibitors has led to US Food and Drug Administration approval of two inhibitors of KRAS(G12C), sotorasib and adagrasib. A study published in Nature reports the development of a first-in-class pan-KRAS-selective inhibitor. Here we comment on the current status of KRAS-targeting approaches.