Abstract：
:A fierce dispute has arisen between the supporters of phenotypic and target-focused screening regarding which path grants the higher probability of successful drug development. A chance to reconcile these two approaches lies in successful target deconvolution (TD) after phenotypic screens. But, despite the panoply of available in vitro TD methods, the task of matching a phenotypically active compound with a biomolecular target remains challenging. Consequently, this review details the latest developments of in silico techniques that expedite TD. Ultimately, the deconvoluted target allows us to reap the benefits of the phenotypic and target-focused approaches.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Heilker R,Lessel U,Bischoff Ddoi
10.1016/j.drudis.2018.10.009subject
Has Abstractpub_date
2019-02-01 00:00:00pages
526-532issue
2eissn
1359-6446issn
1878-5832pii
S1359-6446(18)30155-7journal_volume
24pub_type
杂志文章,评审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：:Kidneys have a major role in normal physiology and metabolic homeostasis. Loss or impairment of kidney function is a common occurrence in several metabolic disorders, including hypertension and diabetes. Chronic kidney disease (CKD) affect nearly 10% of the population worldwide; ranks 18th in the list of causes of dea...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.04.020
更新日期：2017-07-01 00:00:00
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：: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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.07.010
更新日期：2013-01-01 00:00:00
abstract：:There is an urgent need for fresh approaches to the treatment of bacterial infections because of the changing patterns of infectious disease and the emergence of bacterial strains resistant to current antibiotics. Modification of the cell phenotype to sensitize bacteria to components of the hosts' immune system or to ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(02)02498-4
更新日期：2002-11-01 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：: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：:Increasing evidence indicates that extracellular vesicles (EVs) are key players in undesirable cell-cell communication in cancer. However, the release of EVs is not unique to cancer cells; normal cells release EVs to perform physiological roles. Thus, selective inhibition of EV release from cancer cells is desirable. ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.03.006
更新日期：2018-06-01 00:00:00
abstract：:Lack of predictability of clinical efficacy and safety is an important problem facing pharmaceutical research today. Translational PK-PD has the ability to integrate data generated from diverse test platforms during discovery and development in a mechanistic framework. Therefore, successful implementation of translati...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.10.002
更新日期：2007-12-01 00:00:00
abstract：:Proteomic-based techniques provide a powerful tool for identifying the full spectrum of protein targets of a drug, elucidating its mechanism(s) of action, and identifying biomarkers of its efficacy and safety. Herein, we outline the technological advancements in the field, and illustrate the contribution of proteomics...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.03.001
更新日期：2017-06-01 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：:Understanding skin metabolism is important when considering drug discovery and safety assessment. This review compares xenobiotic skin metabolism in ex vivo skin to reconstructed human skin and reconstructed human epidermis models, concentrating on phase I and phase II enzymes. Reports on phase I enzymes are more abun...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.06.002
更新日期：2019-09-01 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：:The eye is afflicted by chronic vision debilitating neovascular disorders, such as age-related macular degeneration, proliferative diabetic retinopathy, and corneal angiogenesis. Photodynamic therapy (PDT) is an innovative, evolving approach for treating neovascular diseases of the eye. PDT refers to the process of ac...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.12.005
更新日期：2008-02-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.05.009
更新日期：2007-07-01 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：: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：:Research consortia in Europe often compete with each other for skills, human and technical resources and, eventually, recognition of the scientific impact of their work. In response to the same EU Horizon2020 call, we received funding for our research project proposals to identify and validate novel drug targets for c...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.01.009
更新日期：2020-04-01 00:00:00
abstract：:Effective cancer treatment remains a significant challenge in human healthcare. Although many different types of cancer therapy have been tested, scientists have now concluded that combinations of drugs, or drugs plus gene therapy, can target multiple pathways to fight cancer. Nanovehicles can increase drug uptake ins...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.06.027
更新日期：2020-08-01 00:00:00
abstract：:With the aging of the general population, there is an increasing need for bone defect repair, prompting the development of reliable alternatives to autologous bone grafting, without the usually associated major drawbacks (i.e., limited volume and severe postoperative pain). Given the crucial role that miRNAs appear to...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.04.007
更新日期：2017-07-01 00:00:00
abstract：:The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologi...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.02.006
更新日期：2008-07-01 00:00:00
abstract：:Owing to their structural diversity, peptides are a unique source of innovative active ingredients. However, their development has been challenging because of their disadvantageous pharmacokinetic (PK) properties. Over the past decade, many attempts have been made to improve the oral bioavailability of peptide drugs. ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2021.01.020
更新日期：2021-01-23 00:00:00
abstract：:The intestinal epithelium is the main barrier restricting the oral delivery of low-permeability drugs. Over recent years, numerous nanocarriers have been designed to improve the efficiency of oral drug delivery. However, the intracellular processes determining the transport of nanocarriers across the intestinal epithe...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.04.007
更新日期：2016-05-01 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
pub_type： 杂志文章
doi：10.1016/j.drudis.2012.05.014
更新日期：2012-06-01 00:00:00
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). ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(98)01299-9
更新日期：1999-05-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.09.010
更新日期：2011-10-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.02.015
更新日期：2007-04-01 00:00:00
abstract：:Telomerase is a ribonucleic reverse transcriptase enzyme that uses an integral RNA component as a template to add tandem telomeric DNA repeats, TTAGGG, at the 3' end of the chromosomes. 85-90% of human tumors and their derived cell lines predominantly express high levels of telomerase, therefore contributing to cancer...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.05.015
更新日期：2019-07-01 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：: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
