abstract：:The popularization of genomic high-throughput technologies is causing a revolution in biomedical research and, particularly, is transforming the field of drug discovery. Systems biology offers a framework to understand the extensive human genetic heterogeneity revealed by genomic sequencing in the context of the netwo...

journal_title：Drug discovery today

authors： Dopazo J

更新日期：2014-02-01 00:00:00

abstract：:Alzheimer's disease (AD) is the most common neurodegenerative disorder among older people. However, no cure or disease-modifying treatments are currently available, and the molecular and cellular mechanisms responsible for the etiology of AD remain under debate. Recent studies suggest that the immune system has a cruc...

journal_title：Drug discovery today

authors： Liu YH,Zeng F,Wang YR,Zhou HD,Giunta B,Tan J,Wang YJ

更新日期：2013-12-01 00:00:00

abstract：:Nonclinical safety testing of new biotherapeutic entities represents its own challenges and opportunities in drug development. Hot topics in this field have been discussed recently at the 2nd Annual BioSafe European General Membership Meeting. In this feature article, discussions on the challenges surrounding the use ...

journal_title：Drug discovery today

authors： Kronenberg S,Baumann A,de Haan L,Hinton HJ,Moggs J,Theil FP,Wakefield I,Singer T

更新日期：2013-12-01 00:00:00

abstract：:Analyzers for in-vitro diagnostic (IVD) testing facilitate the determination of medical information from biological samples. To reach a high quality, the detection reagents have to be dispensed with a high degree of precision and accuracy. A technology change from conventional pipetting systems to contact-free dispens...

journal_title：Drug discovery today

authors： Losleben N,Spinke J,Adler S,Oranth N,Zengerle R

更新日期：2013-11-01 00:00:00

abstract：:In this review, we discuss the methodologies and platform technologies for enhancing the oral bioavailability of poorly soluble drugs. We also highlight the mechanisms of formulation technologies for improving desired physicochemical attributes of active substances. We focus on various commercial technologies, along w...

journal_title：Drug discovery today

authors： Alam MA,Al-Jenoobi FI,Al-Mohizea AM

更新日期：2013-10-01 00:00:00

abstract：:Marketing authorization application dossiers of 17 orphan drugs (ODs) and 51 non-ODs evaluated by the European Medicines Agency (EMA) in the period 2009-2010 were compared. We aimed to identify whether any differences existed between ODs and non-ODs in number and type of deficits brought forward during the EMA review,...

journal_title：Drug discovery today

authors： Putzeist M,Mantel-Teeuwisse AK,Llinares J,Gispen-De Wied CC,Hoes AW,Leufkens HG

更新日期：2013-10-01 00:00:00

abstract：:Model-based drug discovery (MBDDx) aims to build and continuously improve the quantitative understanding of the relation between drug exposure (target engagement) efficacy and safety, to support target validation; to define compound property criteria for lead optimization and safety margins; to set the starting dose; ...

journal_title：Drug discovery today

authors： Visser SA,Aurell M,Jones RD,Schuck VJ,Egnell AC,Peters SA,Brynne L,Yates JW,Jansson-Löfmark R,Tan B,Cooke M,Barry ST,Hughes A,Bredberg U

更新日期：2013-08-01 00:00:00

abstract：:The concept of drug-target residence time has been in focus in recent drug discovery literature. However, few studies consider the combined effect of pharmacokinetics (PK) and binding kinetics (BK) on the duration of effect of a drug. Using a simple model that takes both PK and BK into account, we found that prolongat...

journal_title：Drug discovery today

authors： Dahl G,Akerud T

更新日期：2013-08-01 00:00:00

abstract：:The nuclear receptors constitutive androstane receptor (CAR), pregnane X receptor (PXR) and vitamin D receptor (VDR) control a large array of genes that code for important proteins in humans including metabolic enzymes and transporters. 3D structures for the ligand-binding domain (LBD) of these receptors are abundantl...

journal_title：Drug discovery today

authors： Wu B,Li S,Dong D

更新日期：2013-06-01 00:00:00

abstract：:The operational model of agonism assumes that the maximum effect a particular receptor system can achieve (the Em parameter) is fixed. Em estimates are above but close to the asymptotic maximum effects of endogenous agonists. The concept of Em is contradicted by superagonists and those positive allosteric modulators t...

journal_title：Drug discovery today

authors： Roche D,Gil D,Giraldo J

更新日期：2013-04-01 00:00:00

abstract：:The increasing prevalence of chronic autoimmune-mediated inflammatory diseases (AIMIDs) in ageing western societies is a major challenge for the drug development industry. The current high medical need for more-effective treatments is at least in part caused by our limited understanding of the mechanisms that drive ch...

journal_title：Drug discovery today

authors： 't Hart BA,Chalan P,Koopman G,Boots AM

更新日期：2013-04-01 00:00:00

abstract：:Acute and chronic cough represent one of the most common symptoms of medical importance but effective pharmacotherapy is, to all intents and purposes, absent. Numerous initiatives targeting the recently discovered tussive pathways are in progress. Here, we review the current antitussive armamentarium and provide an up...

journal_title：Drug discovery today

authors： Morjaria JB,Dickinson RS,Morice AH

更新日期：2013-04-01 00:00:00

abstract：:Clinically useful drugs target a relatively small number of proteins that lie within a clearly defined and chemically accessible space. However, many high value biological targets lie outside this chemical space, and an ability to access such 'intractable' targets not amenable to traditional small molecule interventio...

journal_title：Drug discovery today

authors： Barker A,Kettle JG,Nowak T,Pease JE

更新日期：2013-03-01 00:00:00

abstract：:Drug discovery is shifting focus from industry to outside partners and, in the process, creating new bottlenecks. Technologies like high throughput screening (HTS) have moved to a larger number of academic and institutional laboratories in the USA, with little coordination or consideration of the outputs and creating ...

journal_title：Drug discovery today

authors： Ekins S,Waller CL,Bradley MP,Clark AM,Williams AJ

更新日期：2013-03-01 00:00:00

abstract：:Successful drug discovery relies on the selection of drug candidates with good in vivo pharmacokinetic (PK) properties as well as appropriate preclinical efficacy and safety profiles. In vivo PK profiling is often a bottleneck in the discovery process. In this review, we focus on the tiered in vivo PK approaches imple...

journal_title：Drug discovery today

authors： Li C,Liu B,Chang J,Groessl T,Zimmerman M,He YQ,Isbell J,Tuntland T

更新日期：2013-01-01 00:00:00

abstract：:Corneal blindness caused by limbal stem cell deficiency (LSCD) is a prevailing disorder worldwide. Clinical outcomes for LSCD therapy using amniotic membrane (AM) are unpredictable. Hydrogels can eliminate limitations of standard therapy for LSCD, because they present all the advantages of AM (i.e. biocompatibility, i...

journal_title：Drug discovery today

authors： Wright B,Mi S,Connon CJ

更新日期：2013-01-01 00:00:00

abstract：:There is a continuous demand for preclinical modeling of the interaction of dendritic cells with the immune system and cancer cells. Recent progress in gene expression profiling with nucleic acid microarrays, in silico modeling and in vivo cell and animal approaches for non-clinical proof of safety and efficacy of the...

journal_title：Drug discovery today

authors： Imhof M,Karas I,Gomez I,Eger A,Imhof M

更新日期：2013-01-01 00:00:00

abstract：:Huntington's disease (HD) is a progressive and fatal neurodegenerative disease, and the most common inherited CAG repeat disorder. A polyglutamine expansion in the N-terminus of the huntingtin protein (HTT) leads to protein misfolding and downstream pathogenic processes culminating in widespread functional impairment ...

journal_title：Drug discovery today

authors： Appl T,Kaltenbach L,Lo DC,Terstappen GC

更新日期：2012-11-01 00:00:00

abstract：:Neuropathic pain research remains a challenging undertaking owing to: (i) the lack of understanding about the underlying disease processes; and (ii) poor predictive validity of the current models of evoked pain used for the screening of novel compounds. Common consensus is that experimental models replicate symptoms (...

journal_title：Drug discovery today

authors： Taneja A,Di Iorio VL,Danhof M,Della Pasqua O

更新日期：2012-08-01 00:00:00

abstract：:In the past two decades, tuberculosis has gone from being a forgotten disease to a modern and recrudescent pathology. Tuberculosis is a curable infection and most of the negative therapeutic outcomes are related to poor patient compliance, which could be solved by new drug delivery approaches. By using such approaches...

journal_title：Drug discovery today

authors： Dube D,Agrawal GP,Vyas SP

更新日期：2012-07-01 00:00:00

abstract：:In this paper, we review the key solutions that enabled evolution of the lead optimization screening support process at Bristol-Myers Squibb (BMS) between 2004 and 2009. During this time, technology infrastructure investment and scientific expertise integration laid the foundations to build and tailor lead optimizatio...

journal_title：Drug discovery today

authors： Zhang L,Cvijic ME,Lippy J,Myslik J,Brenner SL,Binnie A,Houston JG

更新日期：2012-07-01 00:00:00

abstract：:In recent years there has been a dramatic increase in the number of freely accessible online databases serving the chemistry community. The internet provides chemistry data that can be used for data-mining, for computer models, and integration into systems to aid drug discovery. There is however a responsibility to en...

journal_title：Drug discovery today

authors： Williams AJ,Ekins S,Tkachenko V

更新日期：2012-07-01 00:00:00

abstract：:Atrial fibrillation (AF) is the most common cardiac arrhythmia facing physicians, afflicting 13% of men and 11% of women over 85 years of age. Epidemiological studies estimate that there are ≥ 11 million AF sufferers in the seven major economies and that its prevalence will increase two- to threefold over the next 50 ...

journal_title：Drug discovery today

authors： Milnes JT,Madge DJ,Ford JW

更新日期：2012-07-01 00:00:00

abstract：:Patients with severe asthma suffer persistent symptoms and/or frequent exacerbations despite high-intensity treatment. Their severe unrelenting symptoms have a huge impact on healthcare resources owing to frequent hospital admissions and requirement for intensive treatments. Consequently, there is an undeniable need f...

journal_title：Drug discovery today

authors： Polosa R,Casale T

更新日期：2012-06-01 00:00:00

abstract：:This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. ...

journal_title：Drug discovery today

authors： Satcher R,Evans-Storms RB

更新日期：2012-06-01 00:00:00

abstract：:Medicinal chemistry makes a vital contribution to small molecule drug discovery, and the quality of it contributes directly to research effectiveness as well as to downstream costs, speed and survival in development. In recent years, the discipline of medicinal chemistry has evolved and witnessed many noteworthy contr...

journal_title：Drug discovery today

authors： Johnstone C

更新日期：2012-06-01 00:00:00

abstract：:The occurrence of drug resistance in oncology accounts for treatment failure and relapse of diverse tumor types. Cancers contain cells at various stages of differentiation together with a limited number of 'cancer-initiating cells' able to self-renew and divide asymmetrically, driving tumorigenesis. Cancer-initiating ...

journal_title：Drug discovery today

authors： Alama A,Orengo AM,Ferrini S,Gangemi R

更新日期：2012-05-01 00:00:00

abstract：:Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation. In moderate-to-severe COPD, long-acting bronchodilators are the basis of therapy. Inhaled long-acting β(2)-agonists (LABAs) are used for the treatment of COPD. LABAs have been in use since the 1990s enabling persistent bro...

journal_title：Drug discovery today

authors： Malerba M,Radaeli A,Morjaria JB

更新日期：2012-05-01 00:00:00

abstract：:Senescence forms a universal block to tumorigenesis which impacts on all hallmarks of cancer, making it an attractive target for drug discovery. Therefore a strategy must be devised to focus this broad potential into a manageable drug discovery programme. Several issues remain to be addressed including the lack of rob...

journal_title：Drug discovery today

authors： Cairney CJ,Bilsland AE,Evans TR,Roffey J,Bennett DC,Narita M,Torrance CJ,Keith WN

更新日期：2012-03-01 00:00:00

abstract：: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. In biomedical science, the 'target' is a broad concept ranging from molecular entities (s...

journal_title：Drug discovery today

authors： Yang Y,Adelstein SJ,Kassis AI

更新日期：2012-02-01 00:00:00

abstract：:Concerns emanating from the medical community about the safety and efficacy of biosimilars indicate an increasing distrust of the outcome of the drug regulatory process. To illustrate this, we analysed the creation of the European biosimilar regulatory framework, specifically focussing on the guidelines outlining appr...

journal_title：Drug discovery today

authors： Ebbers HC,Pieters T,Leufkens HG,Schellekens H

更新日期：2012-02-01 00:00:00

abstract：:Fetal hypoxia adversely affects the brain and heart development, yet the mechanisms responsible remain elusive. Recent studies indicate an important role of the extracellular matrix in fetal development and tissue remodeling. The matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of me...

journal_title：Drug discovery today

authors： Tong W,Zhang L

更新日期：2012-02-01 00:00:00

abstract：:Polypharmacology-based strategies are gaining increased attention as a novel approach to obtaining potentially innovative medicines for multifactorial diseases. However, some within the pharmaceutical community have resisted these strategies because they can be resource-hungry in the early stages of the drug discovery...

journal_title：Drug discovery today

authors： Bottegoni G,Favia AD,Recanatini M,Cavalli A

更新日期：2012-01-01 00:00:00

abstract：:After years of hesitation a larger number of pharmaceutical and biotech companies are now supporting the idea of a more individualized pharmacotherapy. The companies that are now involved in this research-demanding area will have to face several challenges. The key factor for success will be an in-depth molecular unde...

journal_title：Drug discovery today

authors： Jørgensen JT

更新日期：2011-10-01 00:00:00

abstract：:SNPs can alter protein function and phenotype, leading to altered pharmacogenomic drug profiles. The exponential number of SNPs makes it impossible to perform wet laboratory experiments to determine the biological significance of each one. However, bioinformatics tools can be used to screen for potentially deleterious...

journal_title：Drug discovery today

authors： Mah JT,Low ES,Lee E

更新日期：2011-09-01 00:00:00

abstract：: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 o...

journal_title：Drug discovery today

authors： Williams AJ,Ekins S

更新日期：2011-09-01 00:00:00

abstract：:Drug-induced liver injury (DILI) is a leading cause of drugs failing during clinical trials and being withdrawn from the market. Comparative analysis of drugs based on their DILI potential is an effective approach to discover key DILI mechanisms and risk factors. However, assessing the DILI potential of a drug is a ch...

journal_title：Drug discovery today

authors： Chen M,Vijay V,Shi Q,Liu Z,Fang H,Tong W

更新日期：2011-08-01 00:00:00

abstract：:The Polo-like kinases (PLKs) have been investigated as oncology targets for several years; however, only recently have potent inhibitors been described. Here, we report on progress in the clinical validation of the PLKs as antitumor drug targets as well as recent understanding gained regarding their synergistic roles ...

journal_title：Drug discovery today

authors： McInnes C,Wyatt MD

更新日期：2011-07-01 00:00:00

abstract：:DNA methylation is an epigenetic change that results in the addition of a methyl group at the carbon-5 position of cytosine residues. The process is mediated by DNA methyltransferases (DNMTs), a family of enzymes for which inhibition is a promising strategy for the treatment of cancer and other diseases. Here, we revi...

journal_title：Drug discovery today

authors： Medina-Franco JL,Caulfield T

更新日期：2011-05-01 00:00:00

abstract：:Osteoarthritis (OA), the most common and disabling form of arthritic disease, is characterized by a slow and progressive degeneration of articular cartilage. Its etiology is multifactorial and includes genetic predisposition, obesity and aging. In addition to the cartilage itself, OA also involves the surrounding tiss...

journal_title：Drug discovery today

authors： De Ceuninck F,Sabatini M,Pastoureau P

更新日期：2011-05-01 00:00:00