Nature Reviews Drug Discovery contents October 2011 Volume 10 Number 10 pp 713-792

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TABLE OF CONTENTS
October 2011 Volume 10 Number 10		Advertisement
Impact Factor 28.712 * Subscribe to Nature Reviews Drug Discovery Recommend to your library	In this issue Comment News and Analysis Research Highlights Perspectives Analysis Reviews Also this month  Featured article: The influence of the 'organizational factor' on compound quality in drug discovery Paul D. Leeson & Stephen A. St-Gallay	Your mission: Conquering cancer. Our mission: Providing the tools. Oncology researchers look to Taconic for the tools they need to advance their research. These tools include one of the industry's broadest, deepest portfolios of xenograft models for immediate delivery, as well as products like the Pirc rat for colon cancer and the CIEA NOG mouse® for humanization studies.
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In this issue p713 | doi:10.1038/nrd3558 Full Text
Comment: Darryle D. Schoepp Where will new neuroscience therapies come from?p715 | doi:10.1038/nrd3559 Abstract | Full Text | PDF
NEWS AND ANALYSIS		Top
Companies hope for kinase inhibitor JAKpot Elie Dolgin p717 | doi:10.1038/nrd3571 Drugs that block Janus kinases are showing promise in diseases ranging from myelofibrosis to rheumatoid arthritis, but with the leading agent in line for approval questions remain about their optimal selectivity. PDF
Gene therapies advance towards finish line Asher Mullard p719 | doi:10.1038/nrd3572 Over a decade since gene therapy development came to a near standstill with the death of a clinical trial participant, the field is overcoming issues of immunogenicity, carcinogenicity, manufacturing and small patient populations. PDF
NEWS IN BRIEF First priority review voucher wasted | Proposed PDUFA V deal unveiled | Lasker rewards natural product drug discovery p721 | doi:10.1038/nrd3573 PDF
BIOBUSINESS BRIEFS Trial watch: IL-13 antibody improves lung function in asthma p722 | doi:10.1038/nrd3562 PDF
Trial watch: First-in-human studies with cardiac myosin activators p722 | doi:10.1038/nrd3563 PDF
Market watch: Upcoming market catalysts in Q4 2011 John Tucker p723 | doi:10.1038/nrd3564 PDF
PATENT WATCH Court considers immunization methods | America Invents Act passed | Viagra patent wards off generic challenge | Oestrogen receptor modulators p724 | doi:10.1038/nrd3574 PDF
AN AUDIENCE WITH Paul Brown p726 | doi:10.1038/nrd3575 Paul Brown, CEO of Roche Molecular Diagnostics, discusses the regulatory and reimbursement concerns that challenge the success of companion diagnostics. PDF
FROM THE ANALYST'S COUCH Antibacterial R&D incentives Ramanan Laxminarayan & John H. Powers p727 | doi:10.1038/nrd3560 PDF
FRESH FROM THE PIPELINE Ezogabine (retigabine) Carl E. Stafstrom, Seden Grippon & Peter Kirkpatrick p729 | doi:10.1038/nrd3561 PDF
RESEARCH HIGHLIGHTS Top Antivirals: Achilles heel of Ebola viral entry p731 | doi:10.1038/nrd3568 PDF Drug repositioning: Genetic signatures uncover new uses p732 | doi:10.1038/nrd3565 PDF Anticancer drugs: Targeting MYC? You BET p732 | doi:10.1038/nrd3569 PDF Antivirals: New clues for flu vaccine design p733 | doi:10.1038/nrd3567 PDF Anticancer drugs: A sweet blow for cancer cells p734 | doi:10.1038/nrd3566 PDF IN BRIEF Protein–protein interactions | Malaria | Cancer | Neuropsychiatric disorders p734 | doi:10.1038/nrd3570 PDF Drug Discovery JOBS of the week Postdoctoral Positions in Computational Biology and Bioinformatics University of Southern California (USC) Los Angeles, US Postdoctoral Fellow - X-ray Crystallography City of Hope - Beckman Research Institute Duarte, US Post-doctoral Fellowship Position at MGH, Harvard Medical School Massachusetts General Hospital, Gastrointestinal Unit Boston, US Senior Scientist BioMarker Strategies Baltimore, US Research Assistant Bioinformatics Institute for Research in Biomedicine Barcelona, ES More Science jobs from Drug Discovery EVENT Active Pharmaceutical Ingredients (API) and Drug Product Specifications 07.-09.12.11 Berlin, Germany More science events from
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PERSPECTIVES		Top
OPINION Integrating predictive biomarkers and classifiers into oncology clinical development programmes Robert A. Beckman, Jason Clark & Cong Chen p735 | doi:10.1038/nrd3550 Predictive biomarkers allow the identification of the subsets of patients who will benefit from a particular drug. However, the development of biomarker–drug combinations requires novel clinical trial designs. In their Perspective, Beckman and colleagues formulate guidelines for the adaptive integration of predictive biomarkers into Phase II/Phase III clinical trials and present strategies to achieve optimal efficiency of such trials. Abstract | Full Text | PDF
ANALYSIS		Top
The influence of the 'organizational factor' on compound quality in drug discovery Paul D. Leeson & Stephen A. St-Gallay p749 | doi:10.1038/nrd3552 In the past 15 years, it has become clear that physicochemical properties of drug candidates, such as lipophilicity and molecular mass, have an important influence on the likelihood of compound-related attrition during development. By analysing the properties of compounds described in patents from leading pharmaceutical companies between 2000 and 2010, this article indicates that a substantial part of the industry has not modified its drug design practices accordingly and is still producing compounds with suboptimal physicochemical profiles. Abstract | Full Text | PDF | Supplementary information
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REVIEWS		Top
Interfering with pH regulation in tumours as a therapeutic strategy Dario Neri & Claudiu T. Supuran p767 | doi:10.1038/nrd3554 The ability of tumour cells to maintain a slightly alkaline intracellular pH and an acidic extracellular pH aids the growth of primary tumours and the formation of metastases. Inhibiting pH-regulating proteins in tumours represents a novel therapeutic strategy that is not exploited by the classical anticancer drugs. Abstract | Full Text | PDF
Development of subtype-selective oestrogen receptor-based therapeutics Stefan Nilsson, Konrad F. Koehler & Jan-Åke Gustafsson p778 | doi:10.1038/nrd3551 Classical selective oestrogen receptor modulators are well established in the treatment of breast cancer and osteoporosis, but emerging knowledge on the oestrogen receptor subtypes α and β suggests that subtype-selective modulators may hold promise for more efficacious and safer treatments of many other diseases and symptoms. Abstract | Full Text | PDF | Supplementary information
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