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Nature Reviews Drug Discovery marks its tenth anniversary this month, providing an opportunity to reflect on the evolution of the landscape of drug research and development (R&D).
Last year saw an upturn in new drug approvals, the end of patent protection for the world's top-selling drug, continued regulatory negotiations and more.
Data on indicators such as the number and success rate of research and development projects illustrate trends in the pharmaceutical industry over the past decade.
Interfacial inhibitors bind to the interfaces of macromolecular machines (for example, polymerases or ribosomes) and stall their progress. A number of natural product and synthetic interfacial inhibitors are in the clinic for the treatment of cancer and bacterial infections. Here, Pommier and Marchand review the concept of interfacial inhibition, and discuss the rationale and methods for the discovery of novel interfacial inhibitors.
Natural antimicrobial peptides defend host organisms against microbes, but most have modest direct antibiotic activity. This article reviews the latest computer-assisted design strategies to develop enhanced peptide variants, and examines emerging data from clinical trials. These broad-spectrum peptides could lead to the development of next-generation antibiotics.
Serine hydrolases are one of the largest and most diverse enzyme classes in nature and have many crucial roles in human physiology and disease. Several serine hydrolases are targets of clinically approved drugs, but many enzymes in this family remain poorly characterized and lack selective inhibitors. Here, Bachovchin and Cravatt discuss the therapeutic potential of serine hydrolases and present novel inhibitor discovery strategies.
Here, the authors highlight the role of proteinase-activated receptors in physiology and in conditions such as cancer and cardiovascular disorders. They also review possible strategies for developing proteinase-activated receptor antagonists and the challenges associated with this goal.
