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 process. Here, we report on fragment-based and computational methods that might accelerate and optimize the discovery of multitarget drugs. In particular, we illustrate that fragment-based approaches can be particularly suited for polypharmacology, owing to the inherent promiscuous nature of fragments. In parallel, we explain how computer-assisted protocols can provide invaluable insights into how to unveil compounds theoretically able to bind to more than one protein. Furthermore, several pragmatic aspects related to the use of these approaches are covered, thus offering the reader practical insights on multitarget-oriented drug discovery projects.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Bottegoni G,Favia AD,Recanatini M,Cavalli Adoi
10.1016/j.drudis.2011.08.002subject
Has Abstractpub_date
2012-01-01 00:00:00pages
23-34issue
1-2eissn
1359-6446issn
1878-5832pii
S1359-6446(11)00253-4journal_volume
17pub_type
杂志文章,评审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
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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
pub_type: 杂志文章,评审
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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
pub_type: 杂志文章,评审
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journal_title:Drug discovery today
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journal_title:Drug discovery today
pub_type: 杂志文章,评审
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journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2012.10.007
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journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03651-2
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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
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journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.06.003
更新日期:2019-09-01 00:00:00
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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::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::Recent failures in efforts to develop an effective vaccine against HIV-1 infection have emphasized the importance of antiretroviral therapy in treating HIV-1-infected patients. Thus far, inhibitors of two viral enzymes, reverse transcriptase and protease, have had a profoundly positive impact on the survival of HIV-1-...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2008.02.003
更新日期:2008-05-01 00:00:00
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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
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journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2015.02.008
更新日期:2015-07-01 00:00:00
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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
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journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2008.09.005
更新日期:2008-12-01 00:00:00
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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::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
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doi:10.1016/j.drudis.2006.05.015
更新日期:2006-07-01 00:00:00
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journal_title:Drug discovery today
pub_type: 杂志文章,评审
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更新日期:2004-02-01 00:00:00
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pub_type: 杂志文章
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journal_title:Drug discovery today
pub_type: 杂志文章,评审
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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...
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pub_type: 杂志文章,评审
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abstract::The stratified medicine companion diagnostic (CDx) cut-off decision integrates scientific, clinical, ethical, and commercial considerations, and determines its value to developers, providers, payers, and patients. Competition already sharpens these issues in oncology, and might soon do the same for emerging stratified...
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abstract::Micro RNAs (miRNAs) are a class of naturally occurring ∼ 22 nt long non-coding small RNA molecules that regulate the expression of a wide range of genes involved in development, growth, proliferation and apoptosis. miRNAs are evolutionarily conserved from plants to animals, and they regulate and fine-tune a diverse ar...
journal_title:Drug discovery today
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doi:10.1016/j.drudis.2010.07.003
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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...
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abstract::Although respiratory syncytial virus (RSV) was discovered in 1955, the burden associated with this infectious agent on all population groups is only now beginning to be fully appreciated. The successful launch of the humanized monoclonal antibody Synagis (developed by MedImmune, Gaithersburg, MD, USA), as a prophylact...
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