Understanding the role of enzymes in disease states and the implementation of strategies to modulate their activities for therapeutic benefit remains a key focus for drug discovery. Here, Holdgate and colleagues assess the benefits of conducting and applying high-quality mechanistic enzymology studies throughout a drug-discovery programme and assess the value of combining such knowledge with orthogonal biophysical methods.

Antibody therapeutics are now established as a major drug class. Here, Carter and Lazar comprehensively discuss current and emerging platforms and technologies for antibody therapeutics, with an emphasis on approaches that could extend their therapeutic applications, including antibody–drug conjugates, bispecific antibodies and antibody engineering to enable more effective delivery.

Lysosomal storage disorders (LSDs) are rare, inherited metabolic disorders that result from defects in lysosomal function, for which treatment options are limited. Here, Platt provides an overview of LSDs, approved and potential therapeutic approaches and agents currently in development. The challenges associated with LSD diagnosis, drug development and treatment are discussed.

Janus kinases (JAKs) are essential signalling mediators downstream of many pro-inflammatory cytokines. Jakinibs — small-molecule inhibitors of JAKs — have gained traction as safe and efficacious options for the treatment of inflammation-driven pathologies. This Review discusses the biology, development and efficacy of jakinibs in the treatment of immune and inflammatory diseases.

Shih and colleagues analyse comprehensive industry-wide data on drug development projects pursued during the past 20 years, classified according to the mechanism and indication for each project. Their findings indicate several points and trends that may be useful in understanding and improving the productivity of the pharmaceutical industry, including areas with substantial success or failure and the relative extent of novelty in completed and ongoing projects.

G protein-coupled receptors (GPCRs) are the most intensively studied class of drug targets. This article presents a pioneering analysis of all GPCR-targeted drugs and agents that are currently in clinical trials, and discusses the trends across molecule types, drug targets and therapeutic indications.

Companies hope the Nobel Prize-winning imaging methodology will reveal biomolecule characteristics that can guide drug discovery projects.