Table of contents
September 2006 Vol 5 No 9
In this issue
p703 | doi:10.1038/nrd2146
Editorial: The end of the beginning?
p705 | doi:10.1038/nrd2147
News and Analysis
Open-access chemistry databases evolving slowly but not surely | PDF (829 KB)
p707 | doi:10.1038/nrd2148
Pfizer hires 'outsider' for insider top job | PDF (88 KB)
p709 | doi:10.1038/nrd2149
News in Brief
| PDF (241 KB)
p710 | doi:10.1038/nrd2150
Patent watch
| Pfizer struggle to protect Lipitor patents | Barr and Shire settle on Adderall | Protease inhibitors | PDF (140 KB)
p712 | doi:10.1038/nrd2151
An Audience With
Robert R. Ruffolo, Jr | PDF (83 KB)
p714 | doi:10.1038/nrd2152
From the analyst's couch
Hepatitis C virus therapies | PDF (275 KB)
p715 | doi:10.1038/nrd2134
Fresh from the Pipeline
Dasatinib | PDF (162 KB)
p717 | doi:10.1038/nrd2135
Research Highlights
Informatics: Exploring pharmacological space | PDF (468 KB)
p719 | doi:10.1038/nrd2140
Neurological disorders: New neurons repair Parkinson's brain | PDF (135 KB)
p720 | doi:10.1038/nrd2138
Kinase inhibitors: Stressed out hearts | PDF (174 KB)
p720 | doi:10.1038/nrd2142
Cancer: Stress can fuel tumour angiogenesis | PDF (140 KB)
p721 | doi:10.1038/nrd2141
Cardiovascular disease: SNP to the rescue? | PDF (94 KB)
p722 | doi:10.1038/nrd2139
In brief
Obesity | Anti-infectives | Biotechnology | Target validation | PDF (86 KB)
p722 | doi:10.1038/nrd2143
Perspectives
Outlook
Can open-source R&D reinvigorate drug research?
Bernard Munos
p723 | doi:10.1038/nrd2131
The open-source software movement has successfully pioneered several strategies that might also be applicable in drug discovery and development. Munos considers the challenges involved, and proposes a model to harness the potential of open-source drug R&D.
Opinion
Drug–target residence time and its implications for lead optimization
Robert A. Copeland, David L. Pompliano & Thomas D. Meek
p730 | doi:10.1038/nrd2082
Pharmacological activity depends on the binding of drugs to their targets. Copeland et al. provide a perspective on the importance of residence time for lead optimization and describe the potential advantages of drugs with a long residence time, in terms of duration of pharmacological effects and selectivity.
Reviews
Model organisms: The mighty mouse: genetically engineered mouse models in cancer drug development
Norman E. Sharpless & Ronald A. DePinho
p741 | doi:10.1038/nrd2110
The poor predictive ability of traditional xenograft mouse models is thought to be a key factor underlying failures of novel cancer drugs in clinical trials. Sharpless and DePinho describe the opportunities and challenges in the application of novel genetically engineered mouse models that more faithfully mimic human cancers, and their potential to improve the success of cancer drug development.
NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential
Oleg V. Evgenov, Pál Pacher, Peter M. Schmidt, György Haskó, Harald H. H. W. Schmidt & Johannes-Peter Stasch
p755 | doi:10.1038/nrd2038
Evgenov et al. review the discovery, biochemistry and pharmacology of nitric oxide-independent stimulators and activators of soluble guanylate cyclase, a key signal-transduction enzyme, and discuss their potential for treating arterial and pulmonary hypertension, heart failure, atherosclerosis, thrombosis, erectile dysfunction, renal fibrosis and failure, and liver cirrhosis.
Anticancer activities of histone deacetylase inhibitors
Jessica E. Bolden, Melissa J. Peart & Ricky W. Johnstone
p769 | doi:10.1038/nrd2133
Johnstone and colleagues discuss the molecular events that underlie the anticancer effects of histone deacetylase inhibitors, and consider how the clinical development and application of these agents may be optimized, either as monotherapies or in combination with other anticancer drugs.
Targeting proteases: successes, failures and future prospects
Boris Turk
p785 | doi:10.1038/nrd2092
Far from being simple degradative enzymes, proteases are now seen as key signalling molecules and desirable drug targets in several diseases. Turk discusses our success so far at targeting proteases and how these enzymes might be exploited therapeutically in the future.
Correspondence
Correspondence: Innovative platinum derived anticancer agents – risk or opportunity?
Steve C.F. Au-Yeung, Patrick S.K. Pang & Yee-ping Ho
| doi:10.1038/nrd1691-c1
Correspondence: Caveats and cautions for the therapeutic targeting of the anti-inflammatory A2 adenosine receptors
Akio Ohta & Michail Sitkovsky
| doi:10.1038/nrd1983-c1
Correspondence: Minimizing disasters during early drug development: A pressing need for an improved guidance
Bernd Jilma & Rashmikant Shah
| doi:10.1038/nrd2050-c1
