Volume 12 Issue 1, January 2013

With multiple drug candidates in the clinic that originated from fragment-based lead discovery, the approach of starting small has become big.

Last year saw the largest loss of revenue yet from major drugs due to patent expiries, but a continuation of 2011's higher level of drug approvals and new initiatives to address R&D challenges provide hope for the future.

Roche is one of the few pharmaceutical companies that has stayed firmly committed to research and development for central nervous system disorders. Here, Luca Santarelli, Senior Vice President and Head of Neuroscience Research and Early development, discusses why.

The last few months have seen a flurry of trial results for investigational agents in Alzheimer's disease (AD). This analysis investigates the different categories of developmental drugs in AD, and provides an outlook to the future of the AD market.

The GPCR Network was established in 2010 with the aim of structurally characterizing 15–25 representative human G protein-coupled receptors (GPCRs) within 5 years; so far, more than eight have been determined. Here, Stevens and colleagues provide an overview of this collaborative effort and the challenges remaining in gaining detailed insights into the structure–function relationships of this receptor superfamily.

Effectively selecting therapeutic targets from the sizeable lists that are emerging from large-scale multi-omics initiatives is a key challenge in drug discovery. This article describes an objective, systematic computational assessment of biological and chemical space that can be applied to any human gene set to prioritize targets for further evaluation, and demonstrates its use on a set of 479 cancer-associated genes to identify new opportunities for drug discovery and repurposing.

Regulatory T (T_Reg) cells are essential mediators of immune homeostasis. They are attractive targets for steering the immune system in desired directions — arming it to destroy cancer cells or downregulating it in autoimmunity. In this Review, Daniel and von Boehmer discuss how molecular insights into the generation and proliferation of these cells can be exploited for new therapeutic approaches.

Most metabolites of the kynurenine pathway — which metabolizes tryptophan — are neuroactive. This Review describes the role of the kynurenine pathway in the pathology of Huntington's disease, migraine and multiple sclerosis, and highlights the most promising compounds that could be of therapeutic value.