Volume 6 Issue 11, November 2007

This year has seen the announcement of a flurry of initiatives intended to encourage innovative biomedical research and development. Bethan Hughes investigates the culture of innovation.

To fully realize the potential of molecularly targeted therapies for cancer and other human diseases, a new level of knowledge about the complex cellular control circuitry is required. Here, the authors explore mathematical paradigms that facilitate the design of network-targeted anticancer drugs.

Despite the wide acceptance of drug-like principles such as the 'rule of five', this analysis of molecules currently being synthesized in leading pharmaceutical companies reveals that their physical properties differ significantly from those of recently discovered oral drugs. The marked increase in lipophilicity in particular could increase the likelihood of attrition in drug development.

Target-based drug discovery has not been as successful as was hoped, in part owing to the complexities of biological systems and disease pathophysiology. This Review explores experimental strategies for the retrospective identification of molecular targets that underlie phenotypic drug effects (target deconvolution) — strategies that might be used to aid efficient drug development.

Genetic factors may underlie susceptibility to serious adverse drug reactions (SADRs). Here, the authors discuss three SADRs — liver injury, myotoxicity and long QT syndrome — and consider the challenges that need to be overcome to identify predisposing genotypes, which might improve patient management.

Hydrogen sulphide (H₂S) is increasingly being recognized as an important signalling molecule in the cardiovascular and nervous systems. This article overviews the physiology and biochemistry of H₂S, summarizes the effects of H₂S inhibitors or H₂S donors in animal models of disease and discusses the likely options and paths for the therapeutic exploitation of H₂S.