abstract：:The prevalence of obesity is increasing at an alarming rate, but, unfortunately, only a few medications are currently on the market. Obesity is primarily regarded as a disorder of lipid metabolism and the enzymes involved in this process could be selectively targeted to develop antiobesity drugs. Recently, newer appro...

journal_title：Drug discovery today

authors： Birari RB,Bhutani KK

更新日期：2007-10-01 00:00:00

abstract：:During the past 10 years, substantial progress has been made in the discovery and development of small molecule glutamate carboxypeptidase II (GCP II) inhibitors. These inhibitors have provided the necessary tools to investigate the physiological role of GCP II as well as the potential therapeutic benefits of its inhi...

journal_title：Drug discovery today

authors： Tsukamoto T,Wozniak KM,Slusher BS

更新日期：2007-09-01 00:00:00

abstract：:This memorandum is addressed to members of regulatory agencies, as well as managers of pharmaceutical companies. Pharmacokineticists and toxicologists may consider this proposal, weigh its merits, and provide input for implementation. Experience from academic research and ADME experiments during drug development has p...

journal_title：Drug discovery today

authors： Stumpf WE

更新日期：2007-08-01 00:00:00

abstract：:Patients can mount sustained immune responses to protein therapeutics with the production of neutralizing antibodies (NAbs) that can compromise efficacy or safety of these drugs. Dendritic cells (DCs) are required for immunoglobulin (Ig) isotype switching and the production of IgG, a process involving presentation of ...

journal_title：Drug discovery today

authors： Barbosa MD,Celis E

更新日期：2007-08-01 00:00:00

abstract：:The physiological levels of many clinically important proteins are regulated through cellular mechanisms that control the stability and translational efficiency of mRNA. These post-transcriptional processes, which play a critical role in the regulation of gene expression, depend on interactions of specific trans-actin...

journal_title：Drug discovery today

authors： Bhattacharyya A,Trotta CR,Peltz SW

更新日期：2007-07-01 00:00:00

abstract：:Here, we detail the major developments in methods and techniques that are applicable to high-throughput synthesis that have evolved over the past five years, with an emphasis on the combination of microwave-based synthesis with techniques such as polymer-assisted purification and immobilized reagents and catalysts. Ot...

journal_title：Drug discovery today

authors： Chighine A,Sechi G,Bradley M

更新日期：2007-06-01 00:00:00

abstract：:Identification and validation of viable targets is an important first step in drug discovery and new methods, and integrated approaches are continuously explored to improve the discovery rate and exploration of new drug targets. An in silico machine learning method, support vector machines, has been explored as a new ...

journal_title：Drug discovery today

authors： Han LY,Zheng CJ,Xie B,Jia J,Ma XH,Zhu F,Lin HH,Chen X,Chen YZ

更新日期：2007-04-01 00:00:00

abstract：:Metabolic determinations are an integral part of every drug-discovery and drug-development program. Recent emphasis has been to increase sample throughput while, at the same time, increase information content within assays. To this end, screening for potential drug-drug interactions, overall metabolic stability and me...

journal_title：Drug discovery today

authors： Castro-Perez JM

更新日期：2007-03-01 00:00:00

abstract：:RNA interference (RNAi) and small-molecule approaches are synergistic on multiple levels, from technology and high-throughput screen development to target identification and functional studies. Here, we describe the RNAi screening platform that we have established and made available to the community through the Drosop...

journal_title：Drug discovery today

authors： Perrimon N,Friedman A,Mathey-Prevot B,Eggert US

更新日期：2007-01-01 00:00:00

abstract：:The modern drug discovery process is steadily becoming more information driven. Structural, physicochemical and ADME-Tox property profiles of reference (successful) ligands, along with structural information of their target proteins, have been extremely useful for early-stage drug discovery. Recently, databases of kno...

journal_title：Drug discovery today

authors： Ghose AK,Herbertz T,Salvino JM,Mallamo JP

更新日期：2006-12-01 00:00:00

abstract：:Multiplexed protein analysis using planar microarrays or microbeads is growing in popularity for simultaneous assays of antibodies, cytokines, allergens, drugs and hormones. However, this new assay format presents several new operational issues for the clinical laboratory, such as the quality control of protein-microa...

journal_title：Drug discovery today

authors： Master SR,Bierl C,Kricka LJ

更新日期：2006-11-01 00:00:00

abstract：:Oral delivery of peptides and proteins remains an attractive alternative to parenteral delivery and has challenged various attempts at delivery development. Incorporation of new tools into the delivery systems that can raise membrane permeability of macromolecules is essential to attain high oral bioavailability that ...

journal_title：Drug discovery today

authors： Morishita M,Peppas NA

更新日期：2006-10-01 00:00:00

abstract：:Some enzymes catalyze the modification of an ensemble of substrates in vivo and, as a consequence, are not ideal targets for active-site-directed drugs. One solution to inhibiting such multisubstrate enzymes would be a drug that binds tightly to only one substrate, which prevents the binding of that substrate to the e...

journal_title：Drug discovery today

authors： Weiss ST,McIntyre NR,McLaughlin ML,Merkler DJ

更新日期：2006-09-01 00:00:00

abstract：:Natural products have been, and continue to be, a major source of pharmacologically active substances from which drugs can be developed. Currently, tumor necrosis factor-alpha (TNF-alpha) inhibitors from natural origins are being advanced for the treatment of inflammatory disorders. Elevated TNF-alpha synthesis has be...

journal_title：Drug discovery today

authors： Paul AT,Gohil VM,Bhutani KK

更新日期：2006-08-01 00:00:00

abstract：:There is an increasing need for systematic cell-based assays in a high-throughput screening (HTS) format to analyze the phenotypic consequences of perturbing mammalian cells with drugs, genes, interfering RNA. Taking advantage of the recent progress in microtechnology, new cell microarrays are being developed and appl...

journal_title：Drug discovery today

authors： Castel D,Pitaval A,Debily MA,Gidrol X

更新日期：2006-07-01 00:00:00

abstract：:The advent of multiple high-throughput technologies has brought drug discovery round almost full circle, from pharmacological testing of compounds in vivo to engineered molecular target assays and back to integrated phenotypic screens in cells and organisms. In the past, primary screens to identify new pharmacological...

journal_title：Drug discovery today

authors： Hall SE

更新日期：2006-06-01 00:00:00

abstract：:Statins are an established therapeutic modality for the treatment of hypercholesterolemia. Although they generally exhibit a good efficacy and tolerability profile, their reputation has been tarnished as a result of reports of myotoxicity and, more recently, observations of proteinuria. The increased incidence of prot...

journal_title：Drug discovery today

authors： Tiwari A

更新日期：2006-05-01 00:00:00

abstract：:Although the 5-hydroxytryptamine(6) (5-HT(6)) receptor was discovered only recently, its almost exclusive distribution in the brain makes it a promising, novel, target for central nervous system (CNS)-mediated diseases such as Alzheimer's disease (cognitive function), schizophrenia, anxiety and obesity. In the past fe...

journal_title：Drug discovery today

authors： Holenz J,Pauwels PJ,Díaz JL,Mercè R,Codony X,Buschmann H

更新日期：2006-04-01 00:00:00

abstract：:To date, the life sciences 'omics' revolution has not lived up to the expectation of boosting the drug discovery process. The major obstacle is dealing with the volume and diversity of data generated. An enhanced-science (e-science) approach based on remote collaboration, reuse of data and methods, and supported by a ...

journal_title：Drug discovery today

authors： Rauwerda H,Roos M,Hertzberger BO,Breit TM

更新日期：2006-03-01 00:00:00

abstract：:Drug discovery is a time consuming and costly process. Recently, a trend towards the use of in silico computational chemistry and molecular modeling for computer-aided drug design has gained significant momentum. This review investigates the application of free and/or open-source software in the drug discovery process...

journal_title：Drug discovery today

authors： Geldenhuys WJ,Gaasch KE,Watson M,Allen DD,Van der Schyf CJ

更新日期：2006-02-01 00:00:00

abstract：:Novel starting points for drug discovery projects are generally found either by screening large collections of compounds or smaller more-focused libraries. Ideally, hundreds or even thousands of actives are initially found, and these need to be reduced to a handful of promising lead series. In several sequential steps...

journal_title：Drug discovery today

authors： Schnecke V,Boström J

更新日期：2006-01-01 00:00:00

abstract：:Annotating the druggable genome estimates the potential maximum size of the playing field for current small-molecule drug design but It does not consider biologicals or future breakthroughs in medicinal chemistry or biology. ...

journal_title：Drug discovery today

authors： Russ AP,Lampel S

更新日期：2005-12-01 00:00:00

abstract：:With the recent explosion of interest in microarray technology, massive amounts of microarray images are currently being produced. The storage and transmission of these types of data are becoming increasingly challenging. This article reviews the latest technologies that allow for the compression and storage of microa...

journal_title：Drug discovery today

authors： Luo Y,Lonardi S

更新日期：2005-12-01 00:00:00

abstract：:The sustained growth of biotechnology in North Carolina has made the state a worldwide leader in biotechnology. ...

journal_title：Drug discovery today

authors： Hartl B

更新日期：2005-11-15 00:00:00

abstract：:Since the Life Science Identifier (LSID) data identification and access standard made its official debut in late 2004, several organizations have begun to use LSIDs to simplify the methods used to uniquely name, reference and retrieve distributed data objects and concepts. In this review, the authors build on introduc...

journal_title：Drug discovery today

authors： Martin S,Hohman MM,Liefeld T

更新日期：2005-11-15 00:00:00

abstract：:The excessive release of glutamate following brain injury is responsible for the phenomenon of glutamate excitotoxicity, mediated through glutamate receptors, resulting in apoptotic cell death. KDI ameliorates excitotoxicity and regenerates damaged nerve cells. ...

journal_title：Drug discovery today

authors： Carney S

更新日期：2005-10-01 00:00:00

abstract：:Gene expression microarrays have been used widely to address increasingly complex biological questions and to produce an unprecedented amount of data, but have yet to realize their full potential. The interpretation of microarray data remains a major challenge because of the complexity of the underlying biological net...

journal_title：Drug discovery today

authors： Imbeaud S,Auffray C

更新日期：2005-09-01 00:00:00

abstract：:Clear links between cancer and cellular signaling triggered by the insulin-like growth factor-I (IGF-I) receptor (IGF-IR) and its cognate ligands (IGF-I and IGF-II) have been reported throughout the past two decades. Experimental results suggest that the pharmaceutical targeting of this signaling pathway could be bene...

journal_title：Drug discovery today

authors： Hofmann F,García-Echeverría C

更新日期：2005-08-01 00:00:00

abstract：:Gastrointestinal patch systems with integrated multifunctions could surmount the challenges associated with conventional drug delivery. Several gastrointestinal patch systems provide bioadhesion, drug protection and unidirectional release. This combination of function could improve the overall oral bioavailability of ...

journal_title：Drug discovery today

authors： Tao SL,Desai TA

更新日期：2005-07-01 00:00:00

abstract：:Cellular life can be represented and studied as the 'interactome'--a dynamic network of biochemical reactions and signaling interactions between active proteins. Systemic networks analysis can be used for the integration and functional interpretation of high-throughput experimental data, which are abundant in drug dis...

journal_title：Drug discovery today

authors： Nikolsky Y,Nikolskaya T,Bugrim A

更新日期：2005-05-01 00:00:00

abstract：:Molecular chirality is a fundamental consideration in drug discovery, one necessary to understand and describe biological targets as well as to design effective pharmaceutical agents. Enantioselective chromatography has played an increasing role not only as an analytical tool for chiral analyses, but also as a prepara...

journal_title：Drug discovery today

authors： Zhang Y,Wu DR,Wang-Iverson DB,Tymiak AA

更新日期：2005-04-15 00:00:00

abstract：:The emergence of a relatively new technique resulting from a combination of frontal affinity chromatography coupled with MS detection (FAC-MS) has extended the capabilities of MS in drug discovery and development. Its application in a broad range of biological systems, together with its label-free operation, relativel...

journal_title：Drug discovery today

authors： Slon-Usakiewicz JJ,Ng W,Dai JR,Pasternak A,Redden PR

更新日期：2005-03-15 00:00:00

abstract：:Our understanding of the detailed recognition and processing of clinically useful therapeutic agents has grown rapidly in recent years, and we are now able to begin to apply this knowledge to the rational treatment of disease. Mammalian carboxylesterases (CEs) are enzymes with broad substrate specificities that have k...

journal_title：Drug discovery today

authors： Redinbo MR,Potter PM

更新日期：2005-03-01 00:00:00

abstract：:One of the world's fastest growing cities, Atlanta is the business center of the Southeast U.S. and is rapidly becoming a leader for biotechnology innovation. ...

journal_title：Drug discovery today

authors： Allen CR

更新日期：2005-02-15 00:00:00

abstract：:In recent years, there have been significant developments made in the way new drugs are being discovered and developed. Such changes are driven by new technologies that have expanded the opportunities to prepare and screen large libraries of compounds in a rapid time frame by the use of high-throughput synthesis and s...

journal_title：Drug discovery today

authors： Potoski J

更新日期：2005-01-15 00:00:00

abstract：:Drug discovery has historically advanced by synergy and chance. These are proving insufficient to meet the needs of the marketplace and the demands of modern medicine. We describe our strategic approaches to building and employing flexible informatics tools to transform and improve the workflows and efficiencies of th...

journal_title：Drug discovery today

authors： Holzman TF,Hebert EJ

更新日期：2005-01-01 00:00:00

abstract：:Microarray-based comparative genomic hybridization (array-CGH) has emerged as a revolutionary platform, enabling the high-resolution detection of DNA copy number aberrations. In this article we outline the use and limitations of genomic clones, cDNA clones and PCR products as targets for genomic microarray constructio...

journal_title：Drug discovery today

authors： Mantripragada KK,Buckley PG,de Ståhl TD,Dumanski JP

更新日期：2004-12-15 00:00:00

abstract：:Posttranslational modifications of proteins such as phosphorylation have been recognized as pivotal modulators of biological activity in healthy and diseased tissues. Sulfation is a key posttranslational modification the role of which in physiology and pathology is only now becoming appreciated. Whereas phosphorylatio...

journal_title：Drug discovery today

authors： Hemmerich S,Verdugo D,Rath VL

更新日期：2004-11-15 00:00:00

abstract：:Hydrocarbon stapling could enable peptides from the key domains of natural proteins to be used therapeutically. Using the technique on a peptide involved in apoptosis, researchers have succeeded in destroying cancer cells in a mouse model of leukaemia. ...

journal_title：Drug discovery today

authors： Whelan J

更新日期：2004-11-01 00:00:00

abstract：:The recent increase in pharmaceutical companies' efforts toward the treatment of obesity reflects recognition of the related health risks, the growth of knowledge about mechanisms that control energy balance, and the potential market for new compounds. The current patent literature gives a picture of the targets that ...

journal_title：Drug discovery today

authors： Jandacek RJ,Woods SC

更新日期：2004-10-15 00:00:00