Articles in 2015

Highlights of deal-making activity in 2014 include divestitures and asset swaps among large pharmaceutical companies, and a slew of cancer immunotherapy alliances.

Randy Mills, head of the California Institute for Regenerative Medicine (CIRM), discusses his plan for the stem-cell therapeutic funding agency.

New therapeutic biologics approved by the US FDA in the past ~30 years have been more innovative on average compared with new small-molecule drugs.

Consortia have begun to establish 'mechanism-based taxonomies' for inflammatory and neurodegenerative diseases that could aid drug development and personalized therapy.

The FDA approved 41 new therapeutics in 2014, but the bumper year fell short of the commercial power of the drugs approved in 2013.

Components of the cell cycle machinery, such as the cyclin-dependent kinases (CDKs), have long been pursued as anticancer targets. Historically, the development of CDK inhibitors has been challenging, but recent developments, particularly in regard to inhibitors for CDK4 and CDK6, have shown promise. This Review presents an overview of the field and discusses agents in clinical development.

The screening of natural products for lead molecules is an attractive strategy, as most natural products fall within biologically relevant chemical space. In this Review, Harvey, Edrada-Ebel and Quinn discuss how advanced screening, metabolomics and metagenomics approaches can be used in the identification, validation and production of naturally sourced compounds, and highlight examples of naturally derived antimicrobials and inhibitors of protein–protein interactions.

Thermodynamic profiling of protein–ligand binding is increasingly used during lead optimization to find ligands that bind with high affinity. In this Perspective, Gerhard Klebe discusses the importance of water, hydrogen bonds, lipophilic contacts and residual mobility in protein–ligand binding, and considers how knowledge of the influence of these factors on the enthalpic and entropic components of the resulting thermodynamic signature can be used in drug design.

Drug delivery methods that use targeted polymeric nanoparticles have the potential to increase local concentrations of a drug while reducing off-target accumulation. To best achieve this goal, Saltzman and colleagues argue that a holistic approach should be taken, in which anatomical, molecular and temporal aspects of the nanoparticle, drug and disease are taken into consideration.