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. This contribution delineates this strategy to minimize the potential for reactive metabolite formation of clinical candidates during preclinical drug optimization, exemplified by the experience at Roche over the past decade. For the majority of research programs it was possible to proceed with compounds optimized for reduced covalent binding potential. Such optimized candidates are expected to have a higher likelihood of succeeding throughout the development processes, resulting in safer drugs.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Brink A,Pähler A,Funk C,Schuler F,Schadt Sdoi
10.1016/j.drudis.2016.11.018subject
Has Abstractpub_date
2017-05-01 00:00:00pages
751-756issue
5eissn
1359-6446issn
1878-5832pii
S1359-6446(16)30440-8journal_volume
22pub_type
杂志文章abstract：:Active immunotherapy of neurodegenerative proteinopathies, such as Alzheimer's disease, requires a Th2 antibody immune response with exclusion of damaging inflammatory Th1 immunity. Because these diseases affect the elderly whom, owing to immunosenescence, are frequently immune compromised, a successful therapy would ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.02.015
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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
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abstract：:Skin is a vital protective organ, the main role of which is to provide a physical barrier and to prevent the entry of pathogens. Various pathologies, such as atopic dermatitis (AD), psoriasis (PSO), or skin cancers, can affect the skin, and all show a high and increasing prevalence. Many antibodies are currently used ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.10.023
更新日期：2021-01-01 00:00:00
abstract：:Gastric bypass surgery is effectively a polypharmacological approach for treatment of obesity, type 2 diabetes and nonalcoholic steatohepatitis (NASH). The gastric bypass mimetic approaches reviewed are fixed-dose combinatorial pharmacological approaches. There are two key concepts incorporated into these gastric bypa...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.04.009
更新日期：2017-08-01 00:00:00
abstract：:A drug has entered clinical trials that contains a recombinant version of the main extract from mistletoe, adn holds promise for cancer patients. ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(02)02571-0
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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
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journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.06.006
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journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2012.12.004
更新日期：2013-04-01 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
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journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.05.022
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.2021.01.020
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journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03692-5
更新日期：2006-02-01 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.2019.11.001
更新日期：2020-01-01 00:00:00
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journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(01)01877-3
更新日期：2001-08-01 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：: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
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journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.05.003
更新日期：2015-08-01 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
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
abstract：:Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(00)01566-x
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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：:Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(01)02006-2
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journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.09.010
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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：:Records about the traditional uses of medicinal plants can be considered useful in bioprospecting (i.e., the search for new active agents or lead structures in nature). Several sources like Egyptian papyri, early modern herbals and pharmacopoeias have been studied in this respect. It is proposed to use recordings of b...
journal_title：Drug discovery today
pub_type： 历史文章,杂志文章
doi：10.1016/j.drudis.2016.11.011
更新日期：2017-05-01 00:00:00
abstract：:Cellular life can be represented and studied as the 'interactome'--a dynamic network of biochemical reactions and signaling interactions between active proteins. Systemic networks analysis can be used for the integration and functional interpretation of high-throughput experimental data, which are abundant in drug dis...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03420-3
更新日期：2005-05-01 00:00:00
abstract：:The recent increase in pharmaceutical companies' efforts toward the treatment of obesity reflects recognition of the related health risks, the growth of knowledge about mechanisms that control energy balance, and the potential market for new compounds. The current patent literature gives a picture of the targets that ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(04)03244-1
更新日期：2004-10-15 00:00:00
abstract：:Three-dimensional (3D) pharmacophore modeling is a technique for describing the interaction of a small molecule ligand with a macromolecular target. Since chemical features in a pharmacophore model are well known and highly transparent for medicinal chemists, these models are intuitively understandable and have been i...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.09.007
更新日期：2008-01-01 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：:To date, the life sciences 'omics' revolution has not lived up to the expectation of boosting the drug discovery process. The major obstacle is dealing with the volume and diversity of data generated. An enhanced-science (e-science) approach based on remote collaboration, reuse of data and methods, and supported by a ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03680-9
更新日期：2006-03-01 00:00:00
