Articles in 2009

Here, the authors use bibliometrics and related data-mining methods to analyse PubMed abstracts, literature citation data and patent filings. The analyses are used to identify trends in disease-related scientific activity that are likely to give new therapeutic opportunities.

The emerging resistance to current antimalarial drugs calls for new strategies to control the disease. This article highlights the potential of targeting the obligate short-lived hepatic forms of the malaria parasite and ways to overcome the challenges of developing drugs that will achieve this.

Although protein kinases are proving to be valuable therapeutic targets for various peripheral-tissue disorders, the development of kinase-targeted therapies for central nervous system (CNS) diseases remains a challenge. Here, Chico and colleagues discuss the issues associated with CNS drug discovery, present trends in small-molecule properties associated with blood–brain barrier penetrance and review emerging CNS protein kinase targets and compounds in development.

Many inhibitors of histone deacetylases (HDACs) are in trials in patients with cancer, but a subset of HDAC inhibitors also have anti-inflammatory or immunosuppressive effects that may be of therapeutic benefit in autoimmune diseases or post-transplantation. Hancock and colleagues describe these effects, highlighting the importance of the ability of some HDAC inhibitors to enhance the production and suppressive functions of FOXP3⁺regulatory T cells, and discuss the potential to develop class- or subclass-specific HDAC inhibitors as novel immunotherapies.

The recent call for the eradication of malaria has sparked the development of new drug classes with improved product profiles. Wells and colleagues review the currently available antimalarials and their limitations, the contribution of genome-based technologies andin vitroscreening of whole parasites to the discovery of new targets, and the issues that should be considered when developing such antimalarials.

Orloff and colleagues describe how moving from the traditional approach to clinical trials based on sequential, distinct phases towards a more integrated strategy that increases flexibility and maximizes the use of accumulated knowledge could have a key role in improving the efficiency and cost-effectiveness of drug development. Using examples in which novel trial designs have been successfully applied, they also illustrate the use of the tools involved, such as Bayesian methodologies, and discuss the advantages and challenges for their more widespread implementation.