Nature Reviews Drug Discovery 7, 458 (2008). doi:10.1038/nrd2441-c1

Author: Johan P. E. Karlberg

We read with interest the recent article in Nature Reviews Drug Discovery on trends in the globalization of clinical trials, as we have also analysed US clinical trial registry data (ClinicalTrials.gov) to study the same topic using data downloaded on 4 April

Nature Reviews Drug Discovery 7, 458 (2008). doi:10.1038/nrd2441-c2

Authors: Fabio A. Thiers, Anthony J. Sinskey & Ernst R. Berndt

Dr Karlberg's correspondence outlines an alternative way of analysing data provided by ClinicalTrials.gov. His results are generally similar to ours, and any differences can be explained by the use of distinct inclusion criteria and formulae for the calculation of trial participation growth rates of

Nature Reviews Drug Discovery 7, 426 (2008). doi:10.1038/nrd2462

Authors: Gerard Sanacora, Carlos A. Zarate, John H. Krystal & Husseini K. Manji

Mood disorders are common, chronic, recurrent mental illnesses that affect the lives of millions of individuals worldwide. To date, the monoaminergic systems (serotonergic, noradrenergic and dopaminergic) in the brain have received the greatest attention in neurobiological studies of mood disorders, and most therapeutics target these

Nature Reviews Drug Discovery 7, 411 (2008). doi:10.1038/nrd2488

Authors: Jeffrey A. Winkles

TWEAK is a multifunctional cytokine that controls many cellular activities including proliferation, migration, differentiation, apoptosis, angiogenesis and inflammation. TWEAK acts by binding to Fn14, a highly inducible cell-surface receptor that is linked to several intracellular signalling pathways, including the nuclear factor-κB (NF-κB) pathway. The TWEAK–Fn14

Nature Reviews Drug Discovery 7, 383 (2008). doi:10.1038/nrd2527

Author: Susan Ward

China was the fastest-growing pharmaceutical market in 2004, with growth rates of 28%, and is forecasted to be the world's largest by 2050 (Ref. 1). Multinational pharmaceutical companies manufactured 40 of the top 50 best-selling drugs. In 2006, the market is estimated to

Nature Reviews Drug Discovery 7, 391 (2008). doi:10.1038/nrd2541

Authors: David M. Goldstein, Nathanael S. Gray & Patrick P. Zarrinkar

To fully exploit the potential of kinases as drug targets, novel strategies for the efficient discovery of inhibitors are required. In contrast to the traditional, linear process of inhibitor discovery, high-throughput kinase profiling enables a parallel approach by interrogating compounds against hundreds of targets in

Nature Reviews Drug Discovery 7, 399 (2008). doi:10.1038/nrd2550

Authors: Chris Jensen, Peter Herold & Hans Rudolf Brunner

The first evidence of the existence of renin was presented over 100 years ago. However, the importance of renin and the renin–angiotensin system in the pathogenesis of cardiovascular disease was only fully realized in the 1970s. It was another 20 years before the first inhibitors

Nature Reviews Drug Discovery 7, 438 (2008). doi:10.1038/nrd2553

Authors: Vincenzo Di Marzo

As our understanding of the endocannabinoids improves, so does the awareness of their complexity. During pathological states, the levels of these mediators in tissues change, and their effects vary from those of protective endogenous compounds to those of dysregulated signals. These observations led to the

Nature Reviews Drug Discovery 7, 458 (2008). doi:10.1038/nrd2569

Author: Charlotte Harrison

Nature Reviews Drug Discovery7, 112 (February 2008) | doi:10.1038/nrd2516This article stated that Caduet is covered by three US patents US 4,681,893 (which covers atorvastatin calcium); 5,273,995 (which covers amlodipine besylate); and 6,455,574 (which covers the product). In

Nature Reviews Drug Discovery 7, 458 (2008). doi:10.1038/nrd2570

Author: Michael P. Manns, Graham R. Foster, Jürgen K. Rockstroh, Stefan Zeuzem, Fabien Zoulim & Michael Houghton

Nature Reviews Drug Discovery6, 991–1000 (December 2007) | doi:10.1038/nrd2411On page 996, in the first paragraph of the right-hand column, which discusses studies with boceprevir, pegIFN-α2a was stated as the pegylated interferon that patients had previously

Nature Reviews Drug Discovery 7, 388 (2008). doi:10.1038/nrd2573

Author: Man Tsuey Tse

A secreted endoglycosidase from Streptococcus pyogenes, EndoS, has been demonstrated to rescue mice from established severe idiopathic thrombocytopenic purpura (ITP).Accumulating evidence indicates that autoantibodies produced by B cells are more important than has previously been appreciated in the development of various autoimmune

Nature Reviews Drug Discovery 7, 387 (2008). doi:10.1038/nrd2574

Author: Bethan Hughes

Parasitic nematodes are an increasing threat to livestock and humans owing to the widespread development of resistance to the three major classes of anthelmintics: benzimidazoles, imidazothiazoles and macrocyclic lactones. Over the past 25 years only one new class has reached the market, the cyclodepsipeptides represented

Nature Reviews Drug Discovery 7, 388 (2008). doi:10.1038/nrd2575

Author: Monica Hoyos Flight

In 2004, the Molecular Libraries Initiative, a programme through which the US National Institutes of Health (NIH) provides academic researchers with access to high-throughput screening (HTS) technologies and expertise, was started. A success arising from the first assay to be accepted for screening by this

Nature Reviews Drug Discovery 7, 389 (2008). doi:10.1038/nrd2576

Author: Sarah Crunkhorn

The heart has the ability to adapt to increased stress by undergoing hypertrophy, but if sustained, heart failure may ensue. Now, two studies in the Journal of Clinical Investigation show that the dietary compound curcumin can block such hypertrophy through the inhibition of p300-histone

Nature Reviews Drug Discovery 7, 390 (2008). doi:10.1038/nrd2577

Author: Charlotte Harrison

Oncogenic mutations in the BRAF gene (such as V600E) correlate with increased severity and decreased response to chemotherapy in several human tumours. Inhibition of oncogenic B-Raf kinase activity could therefore be of therapeutic benefit, and now Tsai and colleagues report the discovery of an

Nature Reviews Drug Discovery 7, 390 (2008). doi:10.1038/nrd2578

Traditional Chinese medicineDissection of mechanisms of Chinese medicinal formula Realgar–Indigo naturalis as an effective treatment for promyelocytic leukemia.Wang, L.et al. Proc. Natl Acad. Sci. USA105, 4826–4831 (2008)To investigate the mechanisms

Nature Reviews Drug Discovery 7, 385 (2008). doi:10.1038/nrd2579

Authors: Hal M. Hoffman, Uma Yasothan & Peter Kirkpatrick

In February 2008, rilonacept (Arcalyst; Regeneron), an interleukin 1 blocker, was approved by the US FDA for the treatment of a group of rare autoinflammatory diseases known as cryopyrin-associated periodic syndromes.

Nature Reviews Drug Discovery 7, 382 (2008). doi:10.1038/nrd2580

boxRecently the FDA issued draft guidance for the development of drugs and therapeutic biologics for the treatment and prevention of diabetes mellitus. What did they recommend and why?Overall, it appears that the FDA is starting to look for more than glycaemic durability as

Nature Reviews Drug Discovery 7, 371 (2008). doi:10.1038/nrd2581

The renin–angiotensin system has a key role in regulating blood pressure, and is the target for several highly successful drugs for cardiovascular disease. However, although renin — the protease at the top of the cascade — has been pursued as a target for more than

Nature Reviews Drug Discovery 7, 373 (2008). doi:10.1038/nrd2582

Author: Stefan H. E. Kaufmann

This year marks the 100th anniversary of the award of the Nobel Prize for Physiology or Medicine to Paul Ehrlich, in recognition of his contribution to immunology. His impact, however, extended far beyond this — for example, in his pioneering research in discovering new anti-infectives,

Nature Reviews Drug Discovery 7, 375 (2008). doi:10.1038/nrd2583

Author: Bethan Hughes

Following the high-profile ENHANCE trial, in which addition of the cardiovascular drug ezetimibe to statin therapy did not result in additional improvement in an imaging-based measure of atherosclerosis, what are the implications for such studies in the future?

Nature Reviews Drug Discovery 7, 376 (2008). doi:10.1038/nrd2584

What are the challenges of conducting statistically valid, as well as clinically meaningful meta-analyses? Dan Jones investigates.

Nature Reviews Drug Discovery 7, 378 (2008). doi:10.1038/nrd2585

Cancer vaccines make progressUS- or EU-approved therapeutic cancer vaccines could be available in 2009.The lowdown: Dendreon received positive news in March 2008 when the FDA agreed to a protocol amendment that would speed up the delivery of the final results of the

Nature Reviews Drug Discovery 7, 380 (2008). doi:10.1038/nrd2586

No new rules at the US patent officeA US district court has decided that proposed changes to how US patents are filed, sought by the US Patent and Trademark Office (PTO), are unlawful. In an attempt to reduce its backlog of patent applications, the

Nature Reviews Drug Discovery 7, 457 (2008). doi:10.1038/nrd2587

Vaccine R&D has been revitalized recently in part owing to major commercial successes and increased incentives for products that address neglected diseases. Our interviewees this month describe the rewards and challenges of their complementary roles in the field.