Nature Reviews Drug Discovery 8, 579 (2009). doi:10.1038/nrd2803

Authors: Dunyaporn Trachootham, Jerome Alexandre & Peng Huang

Increased generation of reactive oxygen species (ROS) and an altered redox status have long been observed in cancer cells, and recent studies suggest that this biochemical property of cancer cells can be exploited for therapeutic benefits. Cancer cells in advanced stage tumours frequently exhibit multiple

Nature Reviews Drug Discovery 8, 533 (2009). doi:10.1038/nrd2923

Authors: Dan Weiss, Prasad Naik & Ram Weiss

Pharmaceutical companies decide how much to invest in developing new drugs and promoting existing ones, thereby influencing the rate of drug discovery and the state of biomedical research funding. The relative emphasis on innovation compared with marketing depends on how these activities affect the

Nature Reviews Drug Discovery 8, 541 (2009). doi:10.1038/nrd2898

Author: Martin Wehling

Drug development projects have high attrition rates, often because efficacy and safety issues have not been foreseen. More effective prediction of 'translational success' could therefore have a key role in addressing the widely acknowledged problems with weak drug development pipelines. Here, I discuss how a

Nature Reviews Drug Discovery 8, 567 (2009). doi:10.1038/nrd2876

Authors: Yan Feng, Timothy J. Mitchison, Andreas Bender, Daniel W. Young & John A. Tallarico

Multi-parameter phenotypic profiling of small molecules provides important insights into their mechanisms of action, as well as a systems level understanding of biological pathways and their responses to small molecule treatments. It therefore deserves more attention at an early step in the drug discovery pipeline.

Nature Reviews Drug Discovery 8, 547 (2009). doi:10.1038/nrd2907

Authors: Silvia Lapenna & Antonio Giordano

Several families of protein kinases orchestrate the complex events that drive the cell cycle, and their activity is frequently deregulated in hyperproliferative cancer cells. Although several molecules that inhibit cell cycle kinases have been developed and clinically screened as potential anticancer agents, none of these

Nature Reviews Drug Discovery 8, 535 (2009). doi:10.1038/nrd2924

Authors: Michael B. Atkins, Uma Yasothan & Peter Kirkpatrick

In March 2009, everolimus (Afinitor; Novartis), an inhibitor of mTOR, was approved by the US FDA for the treatment of patients with advanced kidney cancer.

Nature Reviews Drug Discovery 8, 593 (2009). doi:10.1038/nrd2925

Recent years have seen increased interest in and funding for initiatives that aim to bridge the 'translational gap' between basic and clinical research. Our two interviewees this month discuss the discipline from different vantage points.

Nature Reviews Drug Discovery 8, 530 (2009). doi:10.1038/nrd2928

Author:

Obviousness on the basis of chemical similarityMedicinal chemistry often involves making modifications to previously identified lead compounds to improve biological activity or physicochemical properties. However, to be patentable, a compound must be non-obvious in the context of prior art. So, how can it be

Nature Reviews Drug Discovery 8, 532 (2009). doi:10.1038/nrd2929

MedImmune's Executive Vice President of R&D shares his excitement about the therapeutic potential of novel biologics.

Nature Reviews Drug Discovery 8, 538 (2009). doi:10.1038/nrd2930

Author: Sarah Crunkhorn

Various genetic, behavioural and social factors contribute to the development of obesity. Recently, a possible link between sleep and weight control has emerged. Now, writing in the Journal of Clinical Investigation, Uebele and colleagues identify a novel role for T-type Ca2+ channels

Nature Reviews Drug Discovery 8, 540 (2009). doi:10.1038/nrd2931

Author: Monica Hoyos Flight

The molecular mechanisms underlying human depression are still poorly understood. At present, most drug therapies for this disorder exert their effects by enhancing monamine neurotransmission, but the onset of symptom relief is slow, and many patients fail to achieve full remission. Writing in the Journal

Nature Reviews Drug Discovery 8, 537 (2009). doi:10.1038/nrd2932

Author: Charlotte Harrison

A paper published in Nature Medicine has shown that the G protein-coupled prostanoid EP4 receptor might be a new target for immuno-inflammatory disorders.TH1 and TH17 T helper cells mediate tissue damage and inflammation and are crucial to the pathogenesis

Nature Reviews Drug Discovery 8, 539 (2009). doi:10.1038/nrd2933

Author: Meera Swami

A current priority in cancer research is to identify genetic alterations that are directly involved in tumorigenesis and develop therapies to target them. Arul Chinnaiyan and colleagues have used a prioritization strategy to show that angiotensin II receptor type I (AGTR1) is overexpressed

Nature Reviews Drug Discovery 8, 538 (2009). doi:10.1038/nrd2934

Author: Leonie Welberg

Inhibitors of histone deacetylase (HDAC) enzymes have been shown to improve learning and memory; however, multiple forms of HDAC exist, and the development of more effective HDAC inhibitors would benefit from knowing the specific HDAC(s) that are involved in the regulation of synaptic plasticity. Tsai

Nature Reviews Drug Discovery 8, 540 (2009). doi:10.1038/nrd2935

HIV

Nature Reviews Drug Discovery 8, 528 (2009). doi:10.1038/nrd2936

Amgen has exercised its option to obtain an exclusive worldwide licence to Cytokinetics' cardiac contractility programme, and will pay Cytokinetics US$50 million upfront, and up to $600 million in milestone payments. The programme includes CK-1827452, an inotropic agent with a novel mechanism of action —

Nature Reviews Drug Discovery 8, 528 (2009). doi:10.1038/nrd2937

Johnson & Johnson has bought Cougar Biotechnology, which has a pipeline focused on oncology, for almost US$1 billion. The company's lead compound is abiraterone, an inhibitor of cytochrome P450 17 (CYP17) — an enzyme involved in androgen and oestrogen biosynthesis — which has recently shown

Nature Reviews Drug Discovery 8, 529 (2009). doi:10.1038/nrd2938

Author: Peter Chang

Current pharmacotherapies for obesity have limited efficacy and are associated with concerns over side effects. However, in the third quarter of 2009, mid–late-stage clinical data are due to be reported for a new generation of anti-obesity therapies — mainly novel combinations involving drugs approved for

Nature Reviews Drug Discovery 8, 523 (2009). doi:10.1038/nrd2939

Author: Bethan Hughes

One of the first projects to be selected for funding under the European Innovative Medicines Initiative will address the challenges of developing drugs to treat schizophrenia and depression.

Nature Reviews Drug Discovery 8, 525 (2009). doi:10.1038/nrd2940

Author: Dan Jones

Recent collaborations illustrate approaches to address the challenges of developing therapeutics based on RNA interference.

Nature Reviews Drug Discovery 8, 527 (2009). doi:10.1038/nrd2941

No innovator exclusivity time needed for biologics, says FTCA contentious report on follow-on biologics (FOBs) from the US Federal Trade Commission (FTC) argues against substantial data exclusivity for innovative biologic drugs.The lowdown: Following a round-table meeting in November 2008 examining how FOBs

Nature Reviews Drug Discovery 8, 519 (2009). doi:10.1038/nrd2942

Several initiatives have recently been established to encourage and improve translational research, which could help increase the success rate of drug development projects. A Perspective this month highlights a key issue for translational research in general: how to assess the translational potential of a novel

Nature Reviews Drug Discovery 8, 521 (2009). doi:10.1038/nrd2943

The recent publication of a large clinical trial indicating that the diabetes drug rosiglitazone (Avandia; GlaxoSmithKline) does not increase the risk of cardiovascular morbidity and mortality seems unlikely to end the controversy over its safety. Overall, the story highlights the importance of risk communication in

Nature Reviews Drug Discovery 8, 594 (2009). doi:10.1038/nrd2358-c1

Authors: Jagadeesh Bayry, Sébastien Lacroix-Desmazes & Srini V. Kaveri

In a recent article (Novel therapeutic strategies for multiple sclerosis — a multifaceted adversary. Nature Rev. Drug Discov. 7, 909–925; 2008), Lopez-Diego and Weiner discuss a number of novel potential therapies to treat multiple sclerosis (MS) that target leukocyte trafficking, T

Nature Reviews Drug Discovery 8, 594 (2009). doi:10.1038/nrd2775-c1

Authors: Maurizio Bifulco & Simona Pisanti

The recent News and Analysis article, “End of the line for cannabinoid receptor 1 as an anti-obesity target?” (Nature Rev. Drug Discov. 7, 961–963; 2008) highlighted the downfall of cannabinoid receptor 1 (CB1) blockers for the treatment of obesity, largely