http://www.drugdiscoverytoday.com/ Copyright Elsevier Ltd Intuitiv Ltd (www.intuitiv.net) Sat, 04 Feb 2012 09:23:18 GMT http://www.drugdiscoverytoday.com/ http://www.drugdiscoverytoday.com/_common/img/template/ddt/site-logo.gif http://www.drugdiscoverytoday.com/download/686/ In this article Carmel J. Pezaro, Deborah Mukherji and Johann S. De Bono review the preclinical discovery and clinical development of abiraterone acetate and outline the strategy of parallel translational research. Mon, 23 Jan 2012 00:00:00 GMT http://www.drugdiscoverytoday.com/download/686/ http://www.drugdiscoverytoday.com/download/687/ Neil Jones and Almut Schultz discuss how targeting cancer cell metabolism has emerged as a new area for anticancer drug discovery. Mon, 23 Jan 2012 00:00:00 GMT http://www.drugdiscoverytoday.com/download/687/ http://www.drugdiscoverytoday.com/download/688/ Recent changes to non-clinical cancer guidelines offer a golden opportunity to expedite the translation of new anticancer drugs into the clinic. In this article Paul S. Jones and David Jones look at how these guidelines can be implemented and how they can be integrated with non-clinical and clinical study design to produce robust and safe clinical trials. Mon, 23 Jan 2012 00:00:00 GMT http://www.drugdiscoverytoday.com/download/688/ http://www.drugdiscoverytoday.com/download/689/ In this article Jon Travers, Swee Sharp and Paul Workman evaluate the key role of HSP 90 in enabling the functional and structural stabilisation of a host of client oncoproteins. Mon, 23 Jan 2012 00:00:00 GMT http://www.drugdiscoverytoday.com/download/689/ http://www.drugdiscoverytoday.com/download/671/ The quality of much of the chemical structure-based data introduced to the public domain is poor. The authors of this editorial describe some of the errors found in the recently released NIH Chemical Genomics Center ‘NPC browser’ database as an example. Mon, 12 Dec 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/671/ http://www.drugdiscoverytoday.com/download/667/ In this review the authors have integrated parameters across clinical trials and associated genetic, gene expression and protein data. They provide examples to illustrate the utility of data integration to explore disease heterogeneity and develop predictive biomarkers. Fri, 09 Dec 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/667/ http://www.drugdiscoverytoday.com/download/668/ In this article, the authors describe a combination of structural informatics approaches developed to mine data extracted from existing structure knowledge bases (Protein Data Bank and the GVK database) with a focus on kinase ATP-binding site data. Fri, 09 Dec 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/668/ http://www.drugdiscoverytoday.com/download/669/ This article reviews progress in the development of computational methods, tools and databases used for organizing and extracting biological meaning from antimicrobial research. Fri, 09 Dec 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/669/ http://www.drugdiscoverytoday.com/download/653/ In this review, De Ceuninck et al. highlight the difficulties associated with osteoarthritis diagnosis and discuss the most recent research efforts and successes for the identification of reliable osteoarthritis biomarkers. Wed, 23 Nov 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/653/ http://www.drugdiscoverytoday.com/download/654/ The importance of using translational safety biomarkers that can predict, detect and monitor drug-induced toxicity during human trials is becoming increasingly recognized. In this article Matheis et al. discuss a generic qualification strategy, established by the IMI SAFE-T consortium, for new translational safety biomarkers that will allow early identification, assessment and management of drug-induced injuries throughout R&D. Wed, 23 Nov 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/654/ http://www.drugdiscoverytoday.com/download/655/ Sorani et al. describe a data integration strategy that implements a clinical and biological database and a wiki interface. They integrated parameters across clinical trials and associated genetic, gene expression and protein data. They also provide examples to illustrate the utility of data integration to explore disease heterogeneity and develop predictive biomarkers. Wed, 23 Nov 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/655/ http://www.drugdiscoverytoday.com/download/656/ In this article Michael Nohaile discusses several areas of expertise that need to be considered for drug discovery and translational scientists to use stratification with biomarkers to improve the chances of getting medicines to patients. Wed, 23 Nov 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/656/ http://www.drugdiscoverytoday.com/download/629/ Pavan K Battiprolu et al. discuss insights into mechanisms and molecular events involved in the pathogenesis of diabetic cardiomyopathy. Tue, 18 Oct 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/629/ http://www.drugdiscoverytoday.com/download/630/ Xiaopin Duan and Shirui Mao describe the main barriers preventing nasal insulin absorption, and special attention is given to new approaches to improve the intranasal absorption of insulin, including the application of new safe absorption enhancers and the use of appropriate delivery systems. Tue, 18 Oct 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/630/ http://www.drugdiscoverytoday.com/download/631/ Chen S. Suen and Paul Burn discuss the preclinical and clinical data that have been accumulated to date on incretin-based therapies in type 1 diabetes and type 2 diabetes settings. Tue, 18 Oct 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/631/ http://www.drugdiscoverytoday.com/download/623/ This review highlights some successes in discovery and translation of pharmacogenomic biomarkers for adverse drug events and outlines future strategies to optimize the development and clinical application of pharmacogenomic information. Wed, 21 Sep 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/623/ http://www.drugdiscoverytoday.com/download/624/ This article explores the exciting potential of mitochrondrial pharmacogenetics. Ribosomal RNA (rRNA)-targeting drugs inhibit protein synthesis and represent effective antibiotics for the treatment of infectious diseases. Wed, 21 Sep 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/624/ http://www.drugdiscoverytoday.com/download/620/ Stewart Bates explores how the advent of improved genomic tools has greatly hastened our understanding of the molecular pathology of diseases and how this could enable us to redefine diseases at the molecular level. Together with improved diagnostic criteria, Bates discusses the question: ‘how close is personalized medicine to delivering on its promise?’ Tue, 20 Sep 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/620/ http://www.drugdiscoverytoday.com/download/622/ Hudson and Orviska discuss the views of pharmacogenetics and gene therapy across European countries. Tue, 20 Sep 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/622/ http://www.drugdiscoverytoday.com/download/616/ These are the instructions to authors for submission of articles to Drug Discovery Today Tue, 13 Sep 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/616/ http://www.drugdiscoverytoday.com/download/617/ In the last ten years, public online databases have rapidly become trusted valuable resources upon which researchers rely for their chemical structures and data for use in cheminformatics, bioinformatics, systems biology, translational medicine and now drug repositioning or repurposing efforts. Their utility depends on the quality of the underlying molecular structures used. Unfortunately, the quality of much of the chemical structure-based data introduced to the public domain is poor. As an example we describe some of the errors found in the recently released NIH Chemical Genomics Center ‘NPC browser’ database as an example. There is an urgent need for government funded data curation to improve the quality of internet chemistry and to limit the proliferation of errors and wasted efforts. Tue, 13 Sep 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/617/ http://www.drugdiscoverytoday.com/download/599/ This review focuses on several crucial issues related to those dendrimer features, namely the role of dendrimers as nanoscaffolding and nanocontainers, crucial principles that might be invoked for improving dendrimer cytotoxicity properties, understanding dendrimer cellular transport mechanisms and the exciting role of dendrimers as high-contrast MRI imaging agents. Thu, 01 Sep 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/599/ http://www.drugdiscoverytoday.com/download/600/ This review focuses on the approaches of cancer nanotechnology in the advancement of cancer therapy. Thu, 01 Sep 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/600/ http://www.drugdiscoverytoday.com/download/602/ Nanotechnology-based and advanced therapy medicinal products are at the cutting edge of innovation in translational drug development, potentially offering new treatment approaches for diseases with limited or no therapeutic alternatives. Thu, 01 Sep 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/602/ http://www.drugdiscoverytoday.com/download/604/ This review focuses on the progress of the functionalizations of CNTs, which are the preconditions for CNT applications in medicine, the potential applications of CNTs in the treatment of intractable issues in medicine and the associated potential risks of CNT applications in nanomedicine. Thu, 01 Sep 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/604/ http://www.drugdiscoverytoday.com/download/605/ Current in vivo asthma models are poorly predictive of human disease. In vitro and human model approaches may fill remaining knowledge gaps and pharmaceutical company asthma drug pipelines, whilst reducing reliance on animal models. Thu, 01 Sep 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/605/ http://www.drugdiscoverytoday.com/download/589/ Recent advances in elucidating the cytoplasmic localization and function of ATM are reviewed. Particular attention is given to the role of ATM in insulin signaling and Akt activation. The potential for cytoplasmic ATM protein kinase to be an emerging therapeutic target for treating diabetes, cancer and neuronal degeneration is discussed. Mon, 15 Aug 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/589/ http://www.drugdiscoverytoday.com/download/591/ In this review molecular mechanisms governing transendothelial migration of the diabetogenic effector cells are discussed and resulting pharmacological strategies are considered. Mon, 15 Aug 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/591/ http://www.drugdiscoverytoday.com/download/569/ In this article the author introduces a new concept, termed ‘innovation ASAP’ (iASAP; asking powerful questions, seeking the outliers, accepting defeat and populating astutely) and provides support for it using examples of several successful drugs. Fri, 22 Jul 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/569/ http://www.drugdiscoverytoday.com/download/559/ This article is the third in a series examining the evolution of the market for outsourced lead optimization services and covers developments from late 2006 to the present. Wed, 13 Jul 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/559/ http://www.drugdiscoverytoday.com/download/560/ In this article the authors consider the conditions required for improved organizational creativity and innovation. They also explore whether lean sigma deployment has characteristics that make it inherently anti-innovative or a supportive pro-innovative force. Wed, 13 Jul 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/560/ http://www.drugdiscoverytoday.com/download/539/ This review describes the biological technology of using Lactococcus lactis containing the nisin-modifying enzymes for producing thioether-stabilized therapeutic peptides. Mon, 13 Jun 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/539/ http://www.drugdiscoverytoday.com/download/541/ Inhibition of the proteasome is an effective anti-cancer therapeutic approach, as demonstrated by the first-in-class agent bortezomib. Various new proteasome inhibitors are now in development, including peptide boronic acid analogs MLN9708 and CEP-18770, peptide epoxyketones carfilzomib and PR-047, and NPI-0052, a beta-lactone compound. In this review the authors review the second-generation proteasome inhibitors and assess the potential pharmacologic impact of their different chemical properties. Mon, 13 Jun 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/541/ http://www.drugdiscoverytoday.com/download/534/ This review reports on the unexpected and considerable number of peptides that are currently available as drugs and the chemical strategies that were used to bring them into the market. As demonstrated in this review, peptide-based drug discovery could be a serious option for addressing new therapeutic challenges. Fri, 10 Jun 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/534/ http://www.drugdiscoverytoday.com/download/535/ Peptides capable of mimicking functionally important regions of HIV proteins are excellent tools to explore structure and function of HIV proteins. Recent advances in the design and generation of HIV mimetic peptides are summarized in this article. Fri, 10 Jun 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/535/ http://www.drugdiscoverytoday.com/download/517/ Human nature focuses the scientist on one parameter at a time, yet drug discovery is multidimensional, so to improve our decision making we need tools that can aid in optimizing all key parameters simultaneously. Fri, 13 May 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/517/ http://www.drugdiscoverytoday.com/download/518/ Recent advances in pharmacogenetics, pharmacogenomics and toxicogenomics have 20 increased our knowledge on the genetics and functional genomics of drug metabolizing 21 enzymes. In addition, a wealth of data on drug-related transcriptomics, proteomics and 22 metabolomics has become available. Despite the availability of large amounts of 23 biological information on xenobiotic biotransformation from literature and online 24 resources, the number of available biotransformation pathway maps that can easily be 25 used for visualization of multiple “omics” data, is limited. Fri, 13 May 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/518/ http://www.drugdiscoverytoday.com/download/519/ This review focuses on recent developments in computational toxicology. Direct modeling of toxic endpoints has been deceiving and hampered the wide acceptance of computer predictions. The current trend is to make simpler predictions, closer to the mechanism of action, and to follow them up with in vitro or in vivo assays as appropriate. predictions, closer to the mechanism of action, and to follow them up with in vitro or in vivo assays as appropriate. Fri, 13 May 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/519/ http://www.drugdiscoverytoday.com/download/520/ This article reviews the various approaches that have been used to represent ADME related molecule properties graphically in the context of oral drug-likeness. Fri, 13 May 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/520/ http://www.drugdiscoverytoday.com/download/521/ The availability of high resolution x-ray structures of ADMET relevant proteins might extend the application of structure-based drug design from potency to ADMET prediction. It is however a long way to go and involves an even better understanding of these proteins than is available today. Fri, 13 May 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/521/ http://www.drugdiscoverytoday.com/download/504/ The future of nucleic acid-based therapeutics is dependent on achieving successful delivery. Recently, there has been an increasing interest in delivery via the gastrointestinal tract. Gene therapy via this route has many advantages, including non-invasive access and the versatility to treat local diseases, such as inflammatory bowel disease, as well as systemic diseases, such as haemophilia. Thu, 21 Apr 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/504/ http://www.drugdiscoverytoday.com/download/505/ Lyotropic liquid crystal systems, such as reversed bicontinuous cubic and hexagonal mesophases, are attracting more and more attention because of their unique microstructures and physicochemical properties. Thu, 21 Apr 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/505/ http://www.drugdiscoverytoday.com/download/506/ A short review is proposed on the existing literature for the research performed in calcium phosphate (CaP) biomaterials used as drug delivery systems. In the first part, a brief update is given on the performance of both CaP ceramics and CaP cements. Second, a review of the research and clinical situation is developed for CaP materials already used as drug delivery systems. Thu, 21 Apr 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/506/ http://www.drugdiscoverytoday.com/download/507/ Of the many approaches for the treatment of cancer, angiogenesis and the additional promotion of apoptosis in cancer stem cells by using combinatorial therapy is usually the most recommended. There has been increased interest in the use of antiapoptotic and antiangiogenic biomolecules, such as antiangiogenic microRNA, small interfering RNA, inhibitor of apoptosis protein-binding peptides and Von Hippel-Lindau tumor suppressors, as well as targeting ligands, such as aptamers. Therefore, it is tempting to suggest that such molecules could be used for anticancer therapy. Thu, 21 Apr 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/507/ http://www.drugdiscoverytoday.com/download/488/ Relevance of a drug target for a disease is often inferred with strong belief but fragile evidence. Here, a program for early identification of human diseasespecific drug targets using high-throughput genetic associations is described Wed, 06 Apr 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/488/ http://www.drugdiscoverytoday.com/download/489/ In vivo studies are an important tool for the identification and validation of novel drug targets in medicine; however, the interpretation of submitted and published data is often compromised by inadequate study design. Wed, 06 Apr 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/489/ http://www.drugdiscoverytoday.com/download/490/ Data mining of available biomedical data and information has greatly boosted target discovery in the ‘omics’ era. Target discovery is the key step in the biomarker and drug discovery pipeline to diagnose and fight human diseases. Wed, 06 Apr 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/490/ http://www.drugdiscoverytoday.com/download/491/ Since last reviewed in 2004, the market for outsourcing lead optimization has continued to grow and to change. Here, I review some of the key events that have taken place in this time, particularly merger and acquisition activity, and also seek to delineate some of the emerging trends. Wed, 06 Apr 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/491/ http://www.drugdiscoverytoday.com/download/492/ The optimisation phase is a crucial step in the process of drug development, yet the mechanics of the projects that make it up are poorly understood. Weak documentation of failed projects makes statistical analysis of the factors affecting project performance challenging, so a better approach may be the development of an underlying theory of how projects work. Wed, 06 Apr 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/492/ http://www.drugdiscoverytoday.com/download/493/ We hypothesize that entropy-driven optimizations might be responsible for the undesirable trend observed in physicochemical properties. Consequently, we suggest that enthalpydriven optimizations are preferred because they provide better quality compounds. Wed, 06 Apr 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/493/ http://www.drugdiscoverytoday.com/download/494/ How are drugs discovered and developed? Wed, 06 Apr 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/494/ http://www.drugdiscoverytoday.com/download/481/ Chronic and degenerative disorders are a major, and growing, human health burden, and current treatments are in many cases inadequate or very expensive. Epigenetic therapies are attractive options for treating such disorders because they manipulate the processes that maintain cells in an abnormal transcriptional state. Tue, 29 Mar 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/481/ http://www.drugdiscoverytoday.com/download/483/ This review covers three main areas. Current DNMT inhibitors are discussed first, followed by molecular modeling studies toward the understanding of the mechanism of action of known DNMT inhibitors at the molecular level. Finally, successful virtual screening studies to identify novel small molecule inhibitors are reviewed. Tue, 29 Mar 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/483/ http://www.drugdiscoverytoday.com/download/461/ The pharmaceutical industry, particularly the small molecule domain, faces unprecedented challenges of escalating costs, high attrition as well as increasing competitive pressure from other companies and from new treatment modes such as biological products. In other industries, process improvement approaches, such as Lean Sigma, have delivered benefits in speed, quality and cost of delivery. Examining the medicinal chemistry contributions to the iterative improvement process of design-make-test-analyse from a Lean Sigma perspective revealed that major improvements could be made. Thus, the cycle times of synthesis, as well as compound analysis and purification, were reduced dramatically. Improvements focused on team, rather than individual, performance. These new ways of working have consequences for staff engagement, goals, rewards and motivation, which are also discussed. Fri, 25 Feb 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/461/ http://www.drugdiscoverytoday.com/download/463/ This article deals with the application of computational quantum chemistry to drug design and discovery. Fri, 25 Feb 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/463/ http://www.drugdiscoverytoday.com/download/464/ The article deals with how medicinal chemistry must diversify at pace and in line with the increasing understanding of chemical biology, in order to provide the necessary innovation that the industry requires. Fri, 25 Feb 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/464/ http://www.drugdiscoverytoday.com/download/465/ This article is concerned with the progress of bioinorganic chemistry particularly in the field of cancer. Fri, 25 Feb 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/465/ http://www.drugdiscoverytoday.com/download/466/ This article discusses the medicinal chemistry strategies that have been utilized by the pharmaceutical industry to exploit validated therapeutic targets. Fri, 25 Feb 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/466/ http://www.drugdiscoverytoday.com/download/432/ Drug selectivity is arguably a critical concern for drug development. Recently, experimental evidence suggests that drugs have more selectivity than that afforded by differential affinity for different receptor subtypes. Drugs, acting at a single receptor, can selectively and differentially activate each of the multiple signaling pathways coupled to a receptor. This type of selectivity has been termed functional selectivity. Understanding functional selectivity and how to measure it will be important for new drug development Wed, 19 Jan 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/432/ http://www.drugdiscoverytoday.com/download/435/ Label-free biosensors offer integrated, kinetic and multi-parametric measures of receptor biology and ligand pharmacology in whole cells. Being highly sensitive and pathway-unbiased, label-free receptor assays can be used to probe the systems cell biology including pleiotropic signaling of receptors, and to characterize the functional selectivity and phenotypic pharmacology of ligand molecules. These assays provide a new dimension for elucidating receptor biology and for facilitating drug discovery. Wed, 19 Jan 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/435/ http://www.drugdiscoverytoday.com/download/436/ Transcription factors are promising targets in many therapeutic areas, and reporter assays represent a mainstay of the cellular approaches utilized to study their functions. Traditional reporter assays lend themselves to screening applications, but do suffer from some disadvantages. During the past decade, the development of image-based high-content reporter assays has boosted transcription factor drug discovery and contributed to the understanding of their functions and molecular dynamics. This review summarizes and discusses the technical approaches currently employed in high-content reporter assays. Wed, 19 Jan 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/436/ http://www.drugdiscoverytoday.com/download/437/ Epigenetics refers to heritable changes that control how the genome is accessed in different cell-types and during development and differentiation. Even though each cell contains essentially the same genetic code, epigenetic mechanisms permit specialization of function between cells. The state of chromatin, the complex of histone proteins, RNA and DNA that efficiently package the genome, is largely regulated by specific modifications to histone proteins and DNA, and the recognition of these marks by other proteins and protein complexes. The enzymes that produce these modifications (the ‘writers’), the proteins that recognize them (the ‘readers’), and the enzymes that remove them (the ‘erasers’) are crucial targets for manipulation to further understand the histone code and its role in biology and human disease. Wed, 19 Jan 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/437/ http://www.drugdiscoverytoday.com/download/438/ In recent years significant progress has been made in ourunderstanding of epigenetic control of a wide range of cellular processes. This has come about both through the concerted effort of the research community and through the development of technologies essential to the area. The importance of the epigenetic control of the immune system is becoming increasingly clear, and therefore epigenetics presents itself as an attractive, and potentially ground-breaking, entry point to tackle immune-mediated conditions. The advances in our understanding are in part due to the development of next generation sequencing technologies and chromatin immunoprecipitation. When combined, these approaches have allowed studies at the chromatin level Wed, 19 Jan 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/438/ http://www.drugdiscoverytoday.com/download/439/ Positive allosteric modulation is an innovative strategy for the discovery of drugs acting at 7-transmembrane receptors. Screening has led to the identification of numerous starting points for medicinal chemistry typified by novel mechanisms of action. The progression of compounds through hit-to-candidate phases and preclinical animal models, however, proves very challenging. In this review, we discuss advances in the area and interrogate the mechanistic profiling required to support drug discovery programs and fully exploit the therapeutic potential of positive allosteric modulators. Wed, 19 Jan 2011 00:00:00 GMT http://www.drugdiscoverytoday.com/download/439/ http://www.drugdiscoverytoday.com/download/415/ This article outlines how medicinal chemistry approaches in lead discovery and optimisation can be guided using a thermodynamics approach. Mon, 29 Nov 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/415/ http://www.drugdiscoverytoday.com/download/417/ Ligand efficiency, library design and the uses of the 'Golden Ratio' Mon, 29 Nov 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/417/ http://www.drugdiscoverytoday.com/download/418/ Compound data analysis and computational tools sor SAR mining of large compound data sets. Mon, 29 Nov 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/418/ http://www.drugdiscoverytoday.com/download/389/ Marco D. Sorani, Ward A. Ortmann, Erik P. Bierwagen and Timothy W. Behrens describe a data integration strategy and show how data integration could be used to develop predictive biomarkers. Fri, 29 Oct 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/389/ http://www.drugdiscoverytoday.com/download/390/ Here, Alain J. van Gool, Brian Henry and Erik D. Sprengers outline a rational, question-based drug development strategy in which biomarker data drive decisions on which drug candidates to progress to clinical testing. Fri, 29 Oct 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/390/ http://www.drugdiscoverytoday.com/download/391/ Jens D. Mikkelsen, Morten S. Thomsen, Henrik H. Hansen and Jacek Lichota take a look at the current validity of biomarkers in the identification of novel anti-schizophrenic drug candidates. Fri, 29 Oct 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/391/ http://www.drugdiscoverytoday.com/download/392/ In this article, Jeffrey Cummings, Tim H. Ward and Caroline Dive aim to clarify the issues surrounding biomarker method validation and the analysis of samples and to provide clear guidance on validation strategies. Fri, 29 Oct 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/392/ http://www.drugdiscoverytoday.com/download/393/ A suggestion for a new model of early clinical trial design from Craig P. Carden, Debashis Sarker, Sophie Postel-Vinay, Timothy A. Yap, Gerthardt Attard, Udai Banerji, Michelle D. Garrett, George V. Thomas, Paul Workman, Stan B. Kaye and Johann S. de Bono. Fri, 29 Oct 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/393/ http://www.drugdiscoverytoday.com/download/367/ Elizabeth Foot, Dominique Kleyn and Emma Palmer Foster comment on the debate over the place of pharmacogenetics in the future of drug development, as discussed at the inaugural London Genetics Pharmacogenetic Conference. Thu, 23 Sep 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/367/ http://www.drugdiscoverytoday.com/download/368/ In this interview, conducted by Ulrike Knies-Bamforth, Sir David Weatherall tells Drug Discovery Today about the long-term prospects of personalized medicine, personalized medicine in the third world, and much more. Thu, 23 Sep 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/368/ http://www.drugdiscoverytoday.com/download/370/ Wouter M. Kooloos, Judith A.M. Wessels, Tahar van der Straaten, Tom W.J. Huizinga and Henk-Jan Guchelaar present selection criteria for the pathway pharmacogenetic approach, using adalimumab as a case study. Thu, 23 Sep 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/370/ http://www.drugdiscoverytoday.com/download/371/ Jan Pander, Hans Gelderblom and Henk-Jan Guchelaar provide an overview of germ-line variations in genes that are potentially involved in the pharmacodynamics of the monoclonal antibodies cetuximab, panitumumab and bevacizumab. Thu, 23 Sep 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/371/ http://www.drugdiscoverytoday.com/download/372/ Gavin P. Reynolds discusses genetic variation in responses to antipsychotic drugs and asks whether pharmacogenetics will prove valuable in their discovery. Thu, 23 Sep 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/372/ http://www.drugdiscoverytoday.com/download/374/ Stewart Bates discusses improved genomic tools and other progress towards a new paradigm in drug development, asking: how close is personalized medicine to delivering on its promise? Thu, 23 Sep 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/374/ http://www.drugdiscoverytoday.com/download/347/ Fabrício F. Costa argues that the private sector should start paying more attention to non-coding RNAs to improve the pipeline for drug discovery and drug development and to facilitate the identification of new diagnostic and prognostic markers. Mon, 23 Aug 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/347/ http://www.drugdiscoverytoday.com/download/344/ Head and neck cancers usually present with advanced disease, and novel therapies are urgently needed. Here, Pin-I Huang, Ju-Fang Chang, David H. Kirn and Ta-Chiang Liu summarize the available clinical data and discuss challenges and future directions. Fri, 20 Aug 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/344/ http://www.drugdiscoverytoday.com/download/346/ Sunit Kumar Singh and Praveensingh B. Hajeri discuss the challenges associated with siRNA and the full potential of RNAi for the development of therapeutic tools and drugs. Thu, 19 Aug 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/346/ http://www.drugdiscoverytoday.com/download/345/ Developing precise tools for designing siRNAs can achieve the most efficient knockdown of target genes and reduce off-target effects. Here, Praveensingh B. Hajeri and Sunit Kumar Singh discuss the strategies and parameters required for effective siRNA designing and synthesis. Wed, 18 Aug 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/345/ http://www.drugdiscoverytoday.com/download/250/ This is a white paper addressing the immunotherapeutic potential of the development product Aptocine and puts it in the context of current treatments and other 'cancer vaccines' in development. Mon, 08 Mar 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/250/ http://www.drugdiscoverytoday.com/download/171/ Paul Branthwaite discusses the implication of reducing the Pharmaceutical industry knowledge base as a result of mergers, acquisitions and a drive to reduce cost base. He specificaly deals with the impact of these changes on the ability to produce innovative pharmaceuticals and the time required so to do. Tue, 02 Feb 2010 00:00:00 GMT http://www.drugdiscoverytoday.com/download/171/