Abstract：
:In therapeutic areas aimed at developing an orally administered drug, the pharmacokinetic profile of a drug candidate after oral administration in vivo is pivotal in evaluating its success. This can be done by monitoring the plasma concentration versus time after dosing and calculating the area under the curve (AUC). The authors describe a novel screening protocol in which an estimated AUC can be determined, allowing the rapid evaluation of large numbers of compounds and providing a rank order of estimated AUC values to prioritize compounds for further investigation.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Cox KA,Dunn-Meynell K,Korfmacher WA,Broske L,Nomeir AA,Lin CC,Cayen MN,Barr WHdoi
10.1016/s1359-6446(98)01299-9subject
Has Abstractpub_date
1999-05-01 00:00:00pages
232-237issue
5eissn
1359-6446issn
1878-5832pii
S1359644698012999journal_volume
4pub_type
杂志文章abstract：:Diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) have emerged as effective low-density lipoprotein cholesterol-lowering compounds. Although the results of available epidemiological, preclinical, and clinical...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.01.006
更新日期：2017-06-01 00:00:00
abstract：:Pulmonary arterial hypertension (PAH) has evolved from an untreatable condition to a disease for which several classes of drugs have now been approved, including various prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors. Because the pathogenesis of pulmonary hypertension is increasingly u...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.12.003
更新日期：2009-03-01 00:00:00
abstract：:The function of many key proteins and transcription factors involved in cell growth can be regulated by their cellular localization. Such proteins include the tumor suppressor p53 and the nuclear factor kappaB. Although the idea of trapping such proteins in either the nucleus or cytoplasm has been introduced as a pote...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(02)02562-x
更新日期：2003-01-15 00:00:00
abstract：:Outnumbering our own cells over ten times, gut microbes can even be considered an additional organ. Several studies have explored the association between microbiomes and antitumor drug response. It has been reported that the presence of specific bacteria might modulate cancer progression and the efficacy of anticancer...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.02.009
更新日期：2019-04-01 00:00:00
abstract：:Long-acting drug nanosuspension formulations are coming to the fore as controlled release strategies for several medical conditions and as a preventative measure against HIV infection. However, such delivery systems must, by necessity, be given by hypodermic injection, typically into muscle. This poses problems for pa...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.10.013
更新日期：2018-05-01 00:00:00
abstract：:The Discussion Forum provides a medium for airing your views on any issues related to the pharmaceutical industry and obtaining feedback and discussion on these views from others in the field. You can discuss issues that get you hot under the collar, practical problems at the bench, recently published literature, or j...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(01)01816-5
更新日期：2001-06-01 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：:Atomic force microscopy is being used ever more widely in biological imaging, because of its unique ability to provide structural information at the single molecule level and under near-physiological conditions. Detailed topographic images of potential drug targets, such as proteins and DNA, have been produced, and th...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(03)02905-2
更新日期：2004-01-15 00:00:00
abstract：:An overview of drugs approved by FDA in 2016 reveals dramatic disruptions in long-term trends. The number of new molecular entities (NMEs) dropped, reflecting the lowest rate of small-molecule approvals observed in almost five decades. In addition, the pace of industry consolidation slowed substantially. The impact of...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2017.06.011
更新日期：2017-11-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.09.011
更新日期：2012-02-01 00:00:00
abstract：:Biomedical scientists tend to focus on only a small fraction of the proteins encoded by the human genome despite overwhelming genetic evidence that many understudied proteins are important for human disease. One of the best ways to interrogate the function of a protein and to determine its relevance as a drug target i...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2019.06.020
更新日期：2019-11-01 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
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03703-7
更新日期：2006-01-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.03.012
更新日期：2012-07-01 00:00:00
abstract：:The development of any stem-cell-based therapy (and a potential one for deafness is no exception) relies on the generation of the necessary tools: 'cell drugs' that can be safely manufactured for their clinical application. An increasing body of work has focussed on the identification, in animal models, of potential s...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2010.02.006
更新日期：2010-04-01 00:00:00
abstract：:Carcinomas overexpressing EGFR family receptors are of high clinical importance, because the receptors have prognostic value and are used as molecular targets for anticancer therapy. Insufficient drug efficacy necessitates further in-depth research of the receptor biology and improvement in preclinical stages of drug ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.09.003
更新日期：2019-01-01 00:00:00
abstract：:14-3-3 proteins regulate intracellular signaling pathways, such as signal transduction, protein trafficking, cell cycle, and apoptosis. In addition to the ubiquitous roles of 14-3-3 isoforms, unique tissue-specific functions are also described for each isoform. Owing to their role in regulating cell cycle, protein tra...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.09.012
更新日期：2016-02-01 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：:Fatty acid amide hydrolase (FAAH) is responsible for the hydrolysis of several important endogenous fatty acid amides (FAAs), including anandamide, oleoylethanolamide and palmitoylethanolamide. Because specific FAAs interact with cannabinoid and vanilloid receptors, they are often referred to as 'endocannabinoids' or ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.08.002
更新日期：2009-12-01 00:00:00
abstract：:Benford's law states that the distribution of the first digit of many data sets is not uniform. The first digit of any random number will be 1 almost 30% of the time, and larger digits occur as the first digit with lower and lower frequency, to the point where 9 occurs as a first digit only 5% of the time. Here, we de...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2010.03.003
更新日期：2010-05-01 00:00:00
abstract：:The development of tissue-engineering (TE) solutions for osteochondral (OC) regeneration has been slowed by technical hurdles related to the recapitulation of their complex and hierarchical architecture. OC defects refer to damage of both the articular cartilage and the underlying subchondral bone. To repair an OC tis...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.01.008
更新日期：2018-03-01 00:00:00
abstract：:Opinions about the therapeutic efficacy of medicinal herbs differ significantly. Some reported herbal efficacies at low doses of active ingredients suggest a need for investigating whether these are because of placebo or multi-ingredient synergistic effects. This review discusses the opinions, methods and outcomes of ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.03.012
更新日期：2009-06-01 00:00:00
abstract：:Protein expression therapy using nucleic acid macromolecules (NAMs) as a new paradigm in medicine has recently gained immense therapeutic potential. With the advancement of nonviral delivery it has been possible to target NAMs against cancer, immunodeficiency and infectious diseases. Owing to the complex and fragile s...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.11.012
更新日期：2016-03-01 00:00:00
abstract：:The tumor vasculature transports oxygen, nutrients and drugs for crucial roles in tumor therapy. Antivascular therapy directly targets existing tumor vessels to reduce blood perfusion and then inhibit tumor growth. Vascular disrupting agents and ultrasound-stimulated microbubble destruction use chemical toxicity and p...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.06.001
更新日期：2017-10-01 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：:Glycosaminoglycans (GAGs) are charged polysaccharides ubiquitously present at the cell surface and in the extracellular matrix. GAGs are crucial for cellular homeostasis, and their metabolism is altered during pathological processes. However, little consideration has been given to the regulation of the GAG milieu thro...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.05.010
更新日期：2016-07-01 00:00:00
abstract：:Current multiparameter optimization (MPO) strategies make use of few experimental physicochemical descriptors (i.e., solubility at physiological pH and lipophilicity in the octanol/water system). Here, we show how new trends in drug discovery (i.e., large and flexible molecules for 'difficult' targets) call for the in...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2016.11.017
更新日期：2017-06-01 00:00:00
abstract：:The consensus hypothesis on coronary atherosclerosis suggests high LDL-C levels as the major cause and pursues it as the therapeutic target, explicitly assuming: (i) tunica intima of human coronaries consists of only one cell layer - endothelium, situated on a thin layer of scarcely cellular matrix; and (ii) subendoth...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.05.017
更新日期：2016-10-01 00:00:00
abstract：:The musculoskeletal system is an incredible machine that protects, supports and moves the human body. However, several diseases can limit its functionality, compromising patient quality of life. Designing novel pathological models would help to clarify the mechanisms driving such diseases, identify new biomarkers and ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.04.015
更新日期：2016-09-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.04.004
更新日期：2007-06-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.02.003
更新日期：2011-05-01 00:00:00
