Reviews & Analysis

Analysis of the role of synthetic organic chemistry in the identification of chemical starting points for drug discovery and subsequent optimization into candidate drugs indicates that a small number of reactions and commercially available building blocks dominate. This Perspective highlights opportunities for expanding the synthetic toolbox of medicinal chemists, potentially enabling the more effective exploration of therapeutically relevant chemical space.

Dysregulation of the endocannabinoid system has been implicated in numerous diseases, particularly pain, psychiatric and neurological disorders, but therapeutic intervention in this complex system has proved challenging. In this Perspective article, Di Marzo discusses the lessons learned from the development of drugs that alter endocannabinoid signalling and highlights novel opportunities for pharmacologically manipulating the endocannabinoid system, such as the use of multi-target drugs.

Recent studies have indicated the potential to develop small-molecule drugs that act on RNA targets, leading to burgeoning interest in the field. This article discusses general principles for discovering small-molecule drugs that target RNA and argues that the overarching challenge is to identify appropriate target structures in disease-causing RNAs that have high information content and, consequently, appropriate ligand-binding pockets.