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 metabolite profiles are used early in discovery to select compounds for development. The throttle on the metabolism discovery engine is limited by the time required for data processing and reporting of the information-rich assays used in discovery-stage metabolism studies. In this article I examine how to increase throughput screening in drug discovery using novel liquid chromatography and mass spectrometry as the preferred analytical tool, and potential solutions to maximize output.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Castro-Perez JMdoi
10.1016/j.drudis.2007.01.007subject
Has Abstractpub_date
2007-03-01 00:00:00pages
249-56issue
5-6eissn
1359-6446issn
1878-5832pii
S1359-6446(07)00049-9journal_volume
12pub_type
杂志文章,评审abstract：:The increasing incidence of cutaneous malignancies signifies the need for multiple treatment options. Several available reviews have emphasized the potential role of various botanical extracts and naturally occurring compounds as anti-skin-cancer agents. Few studies relate to the role of chemoprevention and therapeuti...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.11.020
更新日期：2019-02-01 00:00:00
abstract：:The research and development (R&D) of new drugs indicates scientific progress and economic development. However, little is known regarding ongoing or recent clinical trials in China. We analyzed data from clinical trials published before December 31, 2019, and found that the annual registration numbers are increasing ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2020.09.030
更新日期：2020-12-01 00:00:00
abstract：:Rab GTPases constitute the largest family of small GTPases. Rabs regulate not only membrane trafficking but also cell signaling, growth and survival, and development. Increasingly, Rabs and their effectors are shown to be overexpressed or subject to loss-of-function mutations in a variety of disease settings, includin...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.03.012
更新日期：2017-08-01 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
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(04)03277-5
更新日期：2005-01-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.03.017
更新日期：2006-05-01 00:00:00
abstract：:Chemokine receptors control and mediate a diverse array of physiological and pathogenic processes. Many seven transmembrane (TM) G-protein-coupled receptors (GPCRs), including chemokine receptors, exist as homo- or heterodimers. Growing evidence indicates that the dimeric form is the basic functional structure of thes...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.04.004
更新日期：2008-07-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.02.010
更新日期：2012-08-01 00:00:00
abstract：:Following the introduction of antibiotic therapy and widespread inoculations, cardiovascular diseases have leapt ahead of infectious diseases in terms of prevalence in much of the developed and developing world. Herein, we assess FDA-approved drugs for the treatment of cardiovascular diseases. The drug development ent...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2014.09.001
更新日期：2016-01-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.07.005
更新日期：2011-09-01 00:00:00
abstract：:Compelling new evidence supports the idea that regulatory T cells play a major role in our immune system. Several subsets of these regulators have been identified recently. Differences in the phenotypical and functional characteristics of these subsets have immunological implications. From our growing knowledge of the...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(03)03021-6
更新日期：2004-04-01 00:00:00
abstract：:Novel neuroprotective therapies are desperately needed to improve neuronal recovery after ischemic stroke and extend the therapeutic window or offset some of the adverse effects of tissue-type plasminogen activator (tPA). These advances could provide a more effective and safe therapeutic regimen for patients with isch...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.02.011
更新日期：2018-07-01 00:00:00
abstract：:High-information screening formats, using more physiologically relevant cellular models and readout approaches, are slowly replacing traditional, target-orientated approaches in drug discovery programs. With improved access to primary cells, as well as label-free, non-intrusive methods of compound interrogation (such ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2010.02.010
更新日期：2010-05-01 00:00:00
abstract：:To enable the list of genes and proteins contained within genomic databases to be useful for drug discovery, we need to understand how the genome maps into the phenome. An essential, but not explicitly listed ingredient of the genome is the regulatory interactions between genes and proteins that form a genome-wide net...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(02)02463-7
更新日期：2002-10-15 00:00:00
abstract：:Drugs targeting infectious diseases have greatly improved public health. A study to evaluate all US Food and Drug Administration (FDA)-approved new molecular entities (NMEs) reveals that the number of new agents targeting infectious disease peaked during the 1990s and declined rapidly thereafter. Molecules targeting b...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2014.07.005
更新日期：2014-09-01 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
pub_type： 杂志文章
doi：10.1016/j.drudis.2011.05.007
更新日期：2011-08-01 00:00:00
abstract：:Intravitreal injection is one of the major administration routes for the treatment of posterior ocular diseases. Intravitreal therapeutics usually suffer from unsatisfactory efficacy owing to fast clearance from the vitreous humour and insufficient distribution into the retina. Engineered nanoparticles have been appli...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.05.005
更新日期：2019-08-01 00:00:00
abstract：:Decisions in drug development are made on the basis of determinations of cause and effect from experimental observations that span drug development phases. Despite advances in our powers of observation, the ability to determine compound mechanisms from large-scale multi-omic technologies continues to be a major bottle...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2007.10.001
更新日期：2007-11-01 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
pub_type： 杂志文章
doi：10.1016/j.drudis.2011.12.006
更新日期：2012-02-01 00:00:00
abstract：:The endocannabinoid system is implicated in, and regulates, several physiological processes, ranging from food intake and energy balance to pain and inflammation. 2-Arachidonoylglycerol (2-AG) is a full agonist at the cannabinoid receptors which classically mediate its effects. The activity of this bioactive lipid is ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.07.009
更新日期：2014-03-01 00:00:00
abstract：:The explored kinome was extended with broad profiling using the DiscoveRx and Millipore assay panels. The analysis of the profiling of 3368 selected inhibitors on 456 kinases in the DiscoveRx format delivered several insights. First, the coverage depended on the threshold of the selectivity parameter. Second, the rela...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.01.002
更新日期：2015-06-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.08.002
更新日期：2012-01-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.02.007
更新日期：2012-07-01 00:00:00
abstract：:A drug molecule should bind to its target with high affinity and selectivity. Because the binding affinity is a combined function of the binding enthalpy and the binding entropy, extremely high affinity requires that both terms contribute favorably to binding. The binding enthalpy, however, is notoriously more difficu...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.07.005
更新日期：2008-10-01 00:00:00
abstract：:A quantitative analysis has cast doubt over the limited advantages provided by particles for nose-to-brain (NTB) drug delivery. Thus, it is imperative to identify the role of nanovehicles in NTB drug delivery. If nanocarriers are used merely as an option to improve various properties of the drugs or the formulations, ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.01.005
更新日期：2018-05-01 00:00:00
abstract：:The unique anti-atherosclerosis abilities and other cardioprotective properties make high-density lipoprotein (HDL) a promising solution in treating cardiovascular diseases. A number of studies showed that HDL-based therapy was well tolerated and has great potential in the future. Among all these new agents, the most ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.08.010
更新日期：2017-01-01 00:00:00
abstract：:Rare-disease drug development is both scientifically and commercially challenging. This case study highlights Agilis Biotherapeutics (Agilis), a small private biotechnology company that has developed the most clinically advanced adeno-associated virus (AAV) gene therapy for the brain. In an international collaboration...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.12.006
更新日期：2019-03-01 00:00:00
abstract：:The p53 family proteins are among the most appealing targets for cancer therapy. A deeper understanding of the complex interplay that these proteins establish with murine double minute (MDM)2, MDMX, and mutant p53 could reveal new exciting therapeutic opportunities in cancer treatment. Here, we summarize the most rele...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.02.007
更新日期：2016-04-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.01.004
更新日期：2011-05-01 00:00:00
abstract：:Poly(lactic-co-glycolic acid) (PLGA), a US Food and Drug Administration (FDA)-approved copolymer, has been exploited widely in the design of nanoparticles because it is biodegradable, biocompatible, protects the drug molecules from degradation, and aids in producing sustained and targeted delivery. However, certain co...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.09.018
更新日期：2015-01-01 00:00:00
abstract：:There is a continuing need to hasten and improve protein-ligand docking to facilitate the next generation of drug discovery. As the drug-like chemical space reaches into the billions of molecules, increasingly powerful computer systems are required to probe, as well as tackle, the software engineering challenges neede...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.06.023
更新日期：2016-10-01 00:00:00
