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Consortia have begun to establish 'mechanism-based taxonomies' for inflammatory and neurodegenerative diseases that could aid drug development and personalized therapy.
Highlights of deal-making activity in 2014 include divestitures and asset swaps among large pharmaceutical companies, and a slew of cancer immunotherapy alliances.
Butlen-Ducuing and colleagues analyse ~20 years of data on regulatory applications assesssed by the European Medicines Agency in psychiatry and neurology, with the aim of illuminating challenges that underlie the 'pipeline problem' for drugs for central nervous system disorders.
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.
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.
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.
