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 potential therapeutic target, only two nuclear transport inhibitors have been reported. Here, we explore the roles of small-molecule inhibitors that cause target proteins to sequester in either the nucleus or cytoplasm. Methods of artificially targeting proteins to the nucleus or cytoplasm using peptide aptamer technology are also discussed.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Kau TR,Silver PAdoi
10.1016/s1359-6446(02)02562-xsubject
Has Abstractpub_date
2003-01-15 00:00:00pages
78-85issue
2eissn
1359-6446issn
1878-5832pii
S135964460202562Xjournal_volume
8pub_type
杂志文章,评审abstract::For many years, there has been spirited debate as to the relative importance of environmental and genetic factors in the pathogenesis of cancer. Current efforts to annotate the human genome for germ-line genetic variants should establish the foundation for dissecting the contribution of genetics to the risk for cancer...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(04)03179-4
更新日期:2004-07-15 00:00:00
abstract::The successful cloning and subsequent clinical application of recombinant cytokines and/or growth factors has generated a number of important therapeutics. In contrast to the G-protein-coupled receptors, identification of small-molecule agonists of the cytokine and/or growth factor receptor family has proved difficult...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(00)00062-3
更新日期:2000-12-01 00:00:00
abstract::Although many existing methods are used to study the functions of ion channels and to screen lead compounds for important ion-channel targets, new technologies are being developed for improved performance. It is important to identify the advantages and disadvantages of each technology. In this review, we segment the i...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(01)02095-5
更新日期:2001-12-15 00:00:00
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
更新日期:2014-07-01 00:00:00
abstract::Covalent allosteric modulators possess the pharmacological advantages (high potency, extended duration of action and low drug resistance) of covalent ligands and the additional benefit of the higher specificity and lower toxicity of allosteric modulators. This approach is gaining increasing recognition as a valuable t...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.11.013
更新日期:2017-02-01 00:00:00
abstract::Cancer and arthritis present an enormous challenge to society. They share pathogenic pathways that involve extracellular matrix degradation, tissue invasion, and inflammation. Most cancer and arthritis treatments affect normal cell function to cause significant adverse effects in patients. Specific pathways that promo...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.07.009
更新日期:2019-01-01 00:00:00
abstract::Gene expression microarrays have been used widely to address increasingly complex biological questions and to produce an unprecedented amount of data, but have yet to realize their full potential. The interpretation of microarray data remains a major challenge because of the complexity of the underlying biological net...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03565-8
更新日期:2005-09-01 00:00:00
abstract::The biopharmaceutical industry has undergone remarkable changes over the past half century, driven largely by a need to offset the ever-rising costs of developing new medicines. In this report, we aggregated information about the creation and fate of all clinical-stage biopharmaceutical companies, assessing trends ove...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.10.026
更新日期:2021-01-01 00:00:00
abstract::Mice have been excellent surrogates for studying neutrophil biology and, furthermore, murine models of human disease have provided fundamental insights into the roles of human neutrophils in innate immunity. The emergence of novel humanized mice and high-diversity mouse populations offers the research community innova...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.03.018
更新日期:2020-06-01 00:00:00
abstract::In the past five years therapeutic monoclonal antibodies have established themselves as perhaps the most important and rapidly expanding class of therapeutic drugs. More than 25% of pharmacological agents that are currently under development are based on antibodies and the total income generated from them in 2002 exce...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(03)02714-4
更新日期:2003-06-01 00:00:00
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
doi:10.1016/j.drudis.2007.07.024
更新日期:2007-10-01 00:00:00
abstract::Drug-induced liver injury (DILI) is of significant concern to drug development and regulatory review because of the limited success with existing preclinical models. For developing alternative methods, a large drug list is needed with known DILI severity and toxicity. We augmented the DILIrank data set [annotated usin...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.09.022
更新日期:2020-01-01 00:00:00
abstract::Marketing authorization application dossiers of 17 orphan drugs (ODs) and 51 non-ODs evaluated by the European Medicines Agency (EMA) in the period 2009-2010 were compared. We aimed to identify whether any differences existed between ODs and non-ODs in number and type of deficits brought forward during the EMA review,...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2013.06.012
更新日期:2013-10-01 00:00:00
abstract::The increasing prevalence of chronic autoimmune-mediated inflammatory diseases (AIMIDs) in ageing western societies is a major challenge for the drug development industry. The current high medical need for more-effective treatments is at least in part caused by our limited understanding of the mechanisms that drive ch...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.11.010
更新日期:2013-04-01 00:00:00
abstract::Epidermal growth factor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, show excellent clinical efficacy for patients with non-small cell lung cancer (NSCLC) with EGFR mutations, including Exon 19 deletion and single-point substitution, and L858R of exon 21. The reason for the reduction in e...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.10.004
更新日期:2018-03-01 00:00:00
abstract::Psoriasis is a chronic autoimmune skin disorder triggered by either genetic factors, environmental factors, life style, or a combination thereof. Clinical investigations have identified pathogenesis, such as T cell and cytokine-mediated, genetic disposition, antimicrobial peptides, lipocalin-2, galectin-3, vaspin, fra...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.09.023
更新日期:2020-12-01 00:00:00
abstract::Conventional mitogen-activated protein kinase (MAPK) family members are among the most sought-after oncogenic effectors for the development of novel human cancer treatment strategies. MEK5/ERK5 has been the less-studied MAPK subfamily, despite its increasingly demonstrated relevance in the growth, survival, and differ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.06.010
更新日期:2016-10-01 00:00:00
abstract::Alzheimer's disease (AD) is the most common neurodegenerative disorder among older people. However, no cure or disease-modifying treatments are currently available, and the molecular and cellular mechanisms responsible for the etiology of AD remain under debate. Recent studies suggest that the immune system has a cruc...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2013.07.020
更新日期:2013-12-01 00:00:00
abstract::Natural products have been, and continue to be, a major source of pharmacologically active substances from which drugs can be developed. Currently, tumor necrosis factor-alpha (TNF-alpha) inhibitors from natural origins are being advanced for the treatment of inflammatory disorders. Elevated TNF-alpha synthesis has be...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2006.06.002
更新日期:2006-08-01 00:00:00
abstract::Parkinson's disease (PD) is a neurodegenerative pathology of the central nervous system, mainly involving the selective and progressive loss of dopaminergic neurons from the substantia nigra, resulting in motor and non-motor symptoms. PD remains an incurable ailment; thus, treatments are limited to symptom alleviation...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.09.004
更新日期:2019-11-01 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::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...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(04)03261-1
更新日期:2004-11-15 00:00:00
abstract::This memorandum is addressed to members of regulatory agencies, as well as managers of pharmaceutical companies. Pharmacokineticists and toxicologists may consider this proposal, weigh its merits, and provide input for implementation. Experience from academic research and ADME experiments during drug development has p...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2007.06.006
更新日期:2007-08-01 00:00:00
abstract::Chronic infection with hepatitis B virus (HBV) often leads to the development of liver cancer and cirrhosis, creating immense sociological, clinical and economic burdens worldwide. Although current anti-HBV medications manage to control the disease progression and help restore normal liver functions, they often fail t...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2015.01.008
更新日期:2015-05-01 00:00:00
abstract::Rare-disease drug development is both scientifically and commercially challenging. This case study highlights Agilis Biotherapeutics (Agilis), a small private biotechnology company that has developed the most clinically advanced adeno-associated virus (AAV) gene therapy for the brain. In an international collaboration...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.12.006
更新日期:2019-03-01 00:00:00
abstract::For the past decade, the development of genomic technology has revolutionized modern biological research and drug discovery. Functional genomic analyses enable biologists to perform analysis of genetic events on a global scale and they have been widely used in gene discovery, biomarker determination, disease classific...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.05.005
更新日期:2009-08-01 00:00:00
abstract::Data, which help inform various stages of drug product development, are increasingly being collected using newer, more novel platforms, such as mobile applications, and analysed computationally as much larger 'Big Data' data sets, revealing patterns relating to human behaviour and interactions. Medicine acceptability ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2020.12.011
更新日期:2020-12-24 00:00:00
abstract::The energy substrate preference of the human heart is well regulated and is modified upon aging, in that the fetal heart uses glucose, whereas the adult heart utilizes fatty acids. Various human and animal studies suggest a shift in myocardial substrate utilization and decreased rate of myocardial fatty acid uptake an...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.02.010
更新日期:2016-06-01 00:00:00
abstract::Genomics and gene expression data require interpretation at the protein level to validate the biological or pathological findings. To match with the efficiency and capacity of DNA microarray application, methods and approaches of protein analysis in multiplex and high-throughput manner are required for effectively dis...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(03)02655-2
更新日期:2003-04-15 00:00:00
abstract::Many of the drug candidates that fail in clinical trials are withdrawn because of unforeseen effects of human metabolism, such as toxicity and unfavorable pharmacokinetic profiles. Early pre-clinical elimination of such compounds is important but not yet possible. An ideal system would enable researchers to make a con...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(03)02971-4
更新日期:2004-02-01 00:00:00