Nature Reviews Drug Discovery contents February 2015 Volume 14 Number 2 pp 75-149

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TABLE OF CONTENTS
February 2015 Volume 14 Number 2
Impact Factor 37.231 *	In this issue Comment News and Analysis Research Highlights Perspectives Reviews Correspondence Also this month  Featured article: Applying thermodynamic profiling in lead finding and optimization Gerhard Klebe
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BIOPHARMA DEALMAKERS Company Profiles and Partnering Opportunities
Comment: Towards the taxonomy of human disease Martin Hofmann-Apitius, Marta E. Alarcon-Riquelme, Chris Chamberlain & Duncan McHale p75 | doi:10.1038/nrd4537 Consortia have begun to establish 'mechanism-based taxonomies' for inflammatory and neurodegenerative diseases that could aid drug development and personalized therapy. Abstract | Full Text | PDF
NEWS AND ANALYSIS		Top
2014 FDA drug approvals Asher Mullard p77 | doi:10.1038/nrd4545 The FDA approved 41 new therapeutics in 2014, but the bumper year fell short of the commercial power of the drugs approved in 2013. PDF
NEWS IN BRIEF Novartis secures first CRISPR pharma collaborations Asher Mullard p82 | doi:10.1038/nrd4546 PDF
Zafgen charts unique path to obesity approval Asher Mullard p82 | doi:10.1038/nrd4547 PDF
EMA recommended approval for 40 new drugs in 2014 Asher Mullard p82 | doi:10.1038/nrd4548 PDF
BIOBUSINESS BRIEFS Regulatory watch: Innovation in biologic new molecular entities: 1986-2014 Kathleen L. Miller & Michael Lanthier p83 | doi:10.1038/nrd4535 New therapeutic biologics approved by the US FDA in the past ~30 years have been more innovative on average compared with new small-molecule drugs. PDF
BIOBUSINESS BRIEFS Market watch: Biopharma deal-making in 2014: a record year for M&A value Amanda Micklus & Steven Muntner p84 | doi:10.1038/nrd4536 Highlights of deal-making activity in 2014 include divestitures and asset swaps among large pharmaceutical companies, and a slew of cancer immunotherapy alliances. PDF
AN AUDIENCE WITH Randy Mills p86 | doi:10.1038/nrd4538 Randy Mills, head of the California Institute for Regenerative Medicine (CIRM), discusses his plan for the stem-cell therapeutic funding agency. PDF
FROM THE ANALYST'S COUCH European regulatory experience with drugs for central nervous system disorders Florence Butlen-Ducuing, Malgorzata Zienowicz, Frank Pétavy, Manuel Haas, Tomas Salmonson, Hans-Georg Eichler & Guido Rasi p89 | doi:10.1038/nrd4511 Butlen-Ducuing and colleagues analyse ~20 years of data on regulatory applications assesssed by the European Medicines Agency in psychiatry and neurology, with the aim of illuminating challenges that underlie the 'pipeline problem' for drugs for central nervous system disorders. PDF
RESEARCH HIGHLIGHTS Top Obesity and diabetes: FXR and JAK step up to BAT p91 | doi:10.1038/nrd4543 PDF Sleep-related disorders: Expanding the applications of clock-gene modulation p92 | doi:10.1038/nrd4541 PDF Huntington Disease: Banking on ATM p92 | doi:10.1038/nrd4542 PDF Cardiovascular disease: Insulin sensitizer protects the heart p93 | doi:10.1038/nrd4540 PDF Antibacterial drugs: A new drug for resistant bugs p94 | doi:10.1038/nrd4544 PDF IN BRIEF Metabolic disease: Inhibiting serotonin reverses obesity | Viral diseases: Dengue virus vaccine design | Cancer: Targeting drug-resistant melanoma | Obesity: ILC2s promote browning of FAT PDF Drug Discovery JOBS of the week Postdoctoral Fellow (Protein Array and Drug Discovery) Baylor College of Medicine (BCM) Postdoctoral Fellow in Drug Discovery UCLA Postdoctoral Scholar-Pharmaceutical Sciences / Drug Delivery oregon state university More Science jobs from Drug Discovery EVENT RICT 2015: Drug Discovery and Selection - Understanding Targets and Mechanisms 01.07.15 Avignon, France More science events from
PERSPECTIVES		Top
OPINION Applying thermodynamic profiling in lead finding and optimization Gerhard Klebe p95 | doi:10.1038/nrd4486 Thermodynamic profiling of protein-ligand binding is increasingly used during lead optimization to find ligands that bind with high affinity. In this Perspective, Gerhard Klebe discusses the importance of water, hydrogen bonds, lipophilic contacts and residual mobility in protein-ligand binding, and considers how knowledge of the influence of these factors on the enthalpic and entropic components of the resulting thermodynamic signature can be used in drug design. Abstract | Full Text | PDF | Supplementary information
REVIEWS		Top
The re-emergence of natural products for drug discovery in the genomics era Alan L. Harvey, RuAngelie Edrada-Ebel & Ronald J. Quinn p111 | doi:10.1038/nrd4510 The screening of natural products for lead molecules is an attractive strategy, as most natural products fall within biologically relevant chemical space. In this Review, Harvey, Edrada-Ebel and Quinn discuss how advanced screening, metabolomics and metagenomics approaches can be used in the identification, validation and production of naturally sourced compounds, and highlight examples of naturally derived antimicrobials and inhibitors of protein-protein interactions. Abstract | Full Text | PDF
The history and future of targeting cyclin-dependent kinases in cancer therapy Uzma Asghar, Agnieszka K. Witkiewicz, Nicholas C. Turner & Erik S. Knudsen p130 | doi:10.1038/nrd4504 Components of the cell cycle machinery, such as the cyclin-dependent kinases (CDKs), have long been pursued as anticancer targets. Historically, the development of CDK inhibitors has been challenging, but recent developments, particularly in regard to inhibitors for CDK4 and CDK6, have shown promise. This Review presents an overview of the field and discusses agents in clinical development. Abstract | Full Text | PDF | Supplementary information
CORRESPONDENCE		Top
Correspondence: A plan for sustainable funding for US biomedical research Preston Hensley & John L. LaMattina p147 | doi:10.1038/nrd4454-c1 Full Text | PDF
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