Pharma companies becoming more aggressive towards generics firms | PDF (882 KB)

p619 | doi:10.1038/nrd2121

Budget cuts curb Europe's enthusiasm to revive innovation | PDF (183 KB)

p621 | doi:10.1038/nrd2122

Immune Disorders: Oral antibody against autoimmunity | PDF (375 KB)

p631 | doi:10.1038/nrd2120

Neurological disorders: Slicing into stroke therapeutics | PDF (105 KB)

p632 | doi:10.1038/nrd2118

RNA interference: Targeted delivery by an RNA double | PDF (115 KB)

p632 | doi:10.1038/nrd2119

Chemical biology: Modulating molecular gateways | PDF (117 KB)

p633 | doi:10.1038/nrd2126

Anti-obesity drugs: Fighting fat | PDF (79 KB)

p634 | doi:10.1038/nrd2123

Strategies for optimizing combinations of molecularly targeted anticancer agents

Janet E. Dancey & Helen X. Chen

p649 | doi:10.1038/nrd2089

A key issue in anticancer drug development is how best to select and evaluate potential combinations of the rapidly growing number of molecularly targeted drugs. Dancey and Chen consider development strategies for targeted-agent combinations, highlighting challenges for their rational preclinical and clinical evaluation, and discussing possible approaches to overcoming them.

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Phosphodiesterases in the CNS: targets for drug development

Frank S. Menniti, W. Stephen Faraci & Christopher J. Schmidt

p660 | doi:10.1038/nrd2058

Many phosphodiesterases are expressed in the CNS, and are attractive targets for the treatment of psychiatric and neurodegenerative disorders. Menniti et al. review current understanding of the phosphodiesterase gene family in the CNS and the implications of targeting these enzymes in this therapeutic area.

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Current development of mTOR inhibitors as anticancer agents

Sandrine Faivre, Guido Kroemer & Eric Raymond

p671 | doi:10.1038/nrd2062

Following the development of the first mTOR inhibitor that successfully improves therapeutic survival in cancer, Raymond and colleagues look at how novel biomarker identification and the use of multitargeted and multimodality therapies could advance the next generation of these drugs.

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Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond

Hossein A. Ghofrani, Ian H. Osterloh & Friedrich Grimminger

p689 | doi:10.1038/nrd2030

Phosphodiesterase 5 inhibitors augment endogenous nitric oxide signalling, thereby restoring vascular reactivity to diseased blood vessels. Ghofrani and colleagues review the evolution of the PDE5 inhibitor sildenafil from a potential anti-angina drug, to an on-demand oral treatment for erectile dysfunction, and its recent re-positioning as a pulmonary hypertension therapeutic.

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