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 few years a significant research interest has advanced the understanding of the functional roles and the pharmacophore requirements of this receptor. Two 5-HT(6) receptor antagonists have already entered Phase II clinical trials for the enhancement of cognitive function. Since the first discovery of selective ligands for the 5-HT(6) receptor by HTS in 1998, several medicinal-chemistry-driven approaches have delivered highly selective lead structures with well-defined functionalities, starting from either the endogenous ligand 5-HT or the chemical structures identified by HTS. The concept of 'scaffold hopping' has been employed to expand the variability of the available chemical scaffolds and to generate patentable ligands. Supported by pharmacophore models, which have been established recently, the binding and functionality (structure-activity relationships) of the lead structures have been optimized further.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Holenz J,Pauwels PJ,Díaz JL,Mercè R,Codony X,Buschmann Hdoi
10.1016/j.drudis.2006.02.004subject
Has Abstractpub_date
2006-04-01 00:00:00pages
283-99issue
7-8eissn
1359-6446issn
1878-5832pii
S1359-6446(06)00005-5journal_volume
11pub_type
杂志文章,评审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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.10.006
更新日期：2007-01-01 00:00:00
abstract：:Medical oncologists are increasingly using anti-angiogenic drugs, but identifying the best-suited drug and the optimal dosage and schedule for treatment of patients remain challenging issues. Circulating endothelial cells (CECs) and circulating endothelial progenitors (CEPs) are modulated in a variety of diseases incl...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.08.011
更新日期：2007-10-01 00:00:00
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：: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：:Pancreatic cancer is one of the most aggressive and lethal human malignancies. Drug therapies and radiotherapy are used for treatment as adjuvants to surgery, but outcomes remain disappointing. Advances in tissue engineering suggest that 3D cultures can reflect the in vivo tumor microenvironment and can guarantee a ph...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.01.012
更新日期：2017-04-01 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：:Regenerative approaches are promising avenues to effectively cure diseases rather than merely treating symptoms, but are associated with concerns around proliferation in other organs. Given that targeted delivery holds the promise of delivering a drug precisely to its desired site of action, usually with the prospect ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2016.12.004
更新日期：2017-06-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is one of the most complex motor neuron diseases. Even though scientific discoveries are accelerating with an unprecedented pace, to date more than 30 clinical trials have ended with failure and staggering frustration. There are too many compounds that increase life span in mice, bu...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.10.014
更新日期：2014-04-01 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
pub_type： 社论
doi：10.1016/j.drudis.2011.07.007
更新日期：2011-09-01 00:00:00
abstract：:We analyzed a list of the top 100 bestselling drugs as a struggling market for new FDA approvals. Using the time from drug approval by the FDA as a measure of drug age, our analysis showed that the top 100 bestselling drugs are getting older. This reflects the stalled launch of new drugs into the market during recent ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2015.06.015
更新日期：2015-11-01 00:00:00
abstract：:Many pharmaceutical companies aim to reduce reactive metabolite formation by chemical modification at early stages of drug discovery. A practice often applied is the detection of stable trapping products of electrophilic intermediates with nucleophilic trapping reagents to guide rational structure-based drug design. T...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2016.11.018
更新日期：2017-05-01 00:00:00
abstract：:The growing application of nanomaterials in healthcare products (i.e., cosmetics, medical devices, and medicinal products) has encouraged the upgrade of the regulatory framework within the European Community to better control their use and manage the risk of negative effects on human health and environment. Unfortunat...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.01.016
更新日期：2017-06-01 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：:In drug discovery and development (DDD), the efficacy, safety and cost of new chemical entities are the main concerns of the pharmaceutical industry. Continuously updated and stricter recommendations imposed by regulatory authorities result in greater challenges being faced by the industry. Reliable high-throughput te...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.11.001
更新日期：2014-05-01 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：:Idiopathic pulmonary fibrosis (IPF) is a progressive and almost invariably lethal disease that affects primarily older adults. After a decade of negative (or inconsistent) results, two recent clinical trials have demonstrated that slowing disease progression with medication is possible. An improved understanding of di...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.01.001
更新日期：2015-05-01 00:00:00
abstract：:The fact that pharmacokinetic (PK) properties of drugs influence their interaction with protein targets is a principle known for decades. The same cannot be said for the opposite, namely that targets influence the PK properties of drugs. Evidence confirming this possibility is introduced here for the first time, as we...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.09.021
更新日期：2019-12-01 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：:Here, we discuss the biomedical applications of graphene-based nanomaterials (GBNs). We examine graphene and its various derivatives, including graphene, graphene oxides (GOs), reduced graphene oxides (rGOs), graphene quantum dots (GQDs), and graphene composites, and discuss their unique properties related to their bi...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.04.002
更新日期：2017-09-01 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 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.05.007
更新日期：2013-10-01 00:00:00
abstract：:We have recently developed a novel strategy for the rational design of compounds. This 'in silico screening' approach is based on the design and screening of virtual combinatorial libraries. Screening is performed using defined rules derived from a comprehensive description of active and inactive molecules in a releva...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(99)01334-3
更新日期：1999-06-01 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：:Application of humanized xenotransplantation disease models and experimental clinical studies in the context of translational research in drug discovery in dermatology is an opportunity to reduce failure due to lack of efficacy in clinical development stage. ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.10.009
更新日期：2008-03-01 00:00:00
abstract：:The biopharmaceutical industry is characterized by intense competition, high uncertainty, and strong dependence on scientific knowledge. We show that in order to succeed in this industry, firms need to be positioned along three strategic dimensions: the level of inter-firm R&D partnering, the level of diversification,...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2009.04.004
更新日期：2009-08-01 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
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：: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：: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：:Current advances in systems biology suggest a new change of paradigm reinforcing the holistic nature of the drug discovery process. According to the principles of systems biology, a simple drug perturbing a network of targets can trigger complex reactions. Therefore, it is possible to connect initial events with final...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.02.004
更新日期：2017-07-01 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
pub_type： 杂志文章
doi：10.1016/S1359-6446(05)03650-0
更新日期：2005-11-15 00:00:00
