Abstract：
:Patients with severe asthma suffer persistent symptoms and/or frequent exacerbations despite high-intensity treatment. Their severe unrelenting symptoms have a huge impact on healthcare resources owing to frequent hospital admissions and requirement for intensive treatments. Consequently, there is an undeniable need for more-effective and safer medications. Expanding knowledge of innate and adaptive immune responses is leading to the development of novel therapies for severe asthma. Herein, we review efficacy and safety data from human clinical trials of monoclonal antibodies that are approved or under investigation for use in asthma. Future drug candidates directed at key targets and the specific role of monoclonal antibodies in distinctively targeted sub-populations of severe asthmatics will be also discussed.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Polosa R,Casale Tdoi
10.1016/j.drudis.2012.01.012subject
Has Abstractpub_date
2012-06-01 00:00:00pages
591-9issue
11-12eissn
1359-6446issn
1878-5832pii
S1359-6446(12)00014-1journal_volume
17pub_type
杂志文章,评审abstract：:Fatty acid amide hydrolase (FAAH) is responsible for the hydrolysis of several important endogenous fatty acid amides (FAAs), including anandamide, oleoylethanolamide and palmitoylethanolamide. Because specific FAAs interact with cannabinoid and vanilloid receptors, they are often referred to as 'endocannabinoids' or ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.08.002
更新日期：2009-12-01 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：:Bacterial genomics has revealed a plethora of previously unknown targets of potential use in the discovery of novel antibacterial drugs. However, so far little has emerged from this approach. Peptide deformylase is an interesting target that was discovered more than 30 years ago, but was not exploited until recently. ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(01)01925-0
更新日期：2001-09-15 00:00:00
abstract：:The irreversible glycation and oxidation of proteins and lipids produces advanced glycation end products (AGEs). These modified AGEs are triggered to bind the receptor for AGE (RAGE), thereby activating its downstream signaling pathways, such as nuclear factor (NF)-κB and phosphoinositide 3-kinase (PI3K)/Akt, ultimate...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.07.003
更新日期：2020-09-01 00:00:00
abstract：:Multiplexed protein analysis using planar microarrays or microbeads is growing in popularity for simultaneous assays of antibodies, cytokines, allergens, drugs and hormones. However, this new assay format presents several new operational issues for the clinical laboratory, such as the quality control of protein-microa...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.09.010
更新日期：2006-11-01 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：:DNA-nanorobot-guided thrombin-inducing tumor infarction (DNA NanorobotTh-ITI) is emerging as a powerful therapeutic strategy for treatment of solid cancers. The technology represents a major advance in the application of DNA nanotechnology for anticancer therapy. More importantly, the technology is being translated fr...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2020.03.005
更新日期：2020-06-01 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：:Depending on the timing of market entry, radical innovations can be distinguished from incremental innovations. Whereas a radical innovation typically is the first available derivative of a drug class, incremental innovations are launched later and show a certain benefit compared with the radical innovation. Here, we ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.09.009
更新日期：2018-02-01 00:00:00
abstract：:Biomedical scientists tend to focus on only a small fraction of the proteins encoded by the human genome despite overwhelming genetic evidence that many understudied proteins are important for human disease. One of the best ways to interrogate the function of a protein and to determine its relevance as a drug target i...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2019.06.020
更新日期：2019-11-01 00:00:00
abstract：:For drug discovery, historical experience is always of significance. Through examining the history of traditional medicines, we find that these medicines have more implications for drug discovery than just providing new chemical entities. The history of traditional medicines indicates that they depended more on the co...
journal_title：Drug discovery today
pub_type： 历史文章,杂志文章
doi：10.1016/j.drudis.2008.07.002
更新日期：2009-02-01 00:00:00
abstract：:Glycosaminoglycans (GAGs) are charged polysaccharides ubiquitously present at the cell surface and in the extracellular matrix. GAGs are crucial for cellular homeostasis, and their metabolism is altered during pathological processes. However, little consideration has been given to the regulation of the GAG milieu thro...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.05.010
更新日期：2016-07-01 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：:Intravitreal injection is one of the major administration routes for the treatment of posterior ocular diseases. Intravitreal therapeutics usually suffer from unsatisfactory efficacy owing to fast clearance from the vitreous humour and insufficient distribution into the retina. Engineered nanoparticles have been appli...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.05.005
更新日期：2019-08-01 00:00:00
abstract：:Gastrointestinal patch systems with integrated multifunctions could surmount the challenges associated with conventional drug delivery. Several gastrointestinal patch systems provide bioadhesion, drug protection and unidirectional release. This combination of function could improve the overall oral bioavailability of ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03489-6
更新日期：2005-07-01 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
更新日期：2001-11-15 00:00:00
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
更新日期：2015-01-01 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：:The Polo-like kinases (PLKs) have been investigated as oncology targets for several years; however, only recently have potent inhibitors been described. Here, we report on progress in the clinical validation of the PLKs as antitumor drug targets as well as recent understanding gained regarding their synergistic roles ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.05.002
更新日期：2011-07-01 00:00:00
abstract：:The popularity of machine learning (ML) across drug discovery continues to grow, yielding impressive results. As their use increases, so do their limitations become apparent. Such limitations include their need for big data, sparsity in data, and their lack of interpretability. It has also become apparent that the tec...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.12.003
更新日期：2020-12-05 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：:Neurodegenerative diseases (NDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), threaten the health of an ever-growing number of older people worldwide; so far, there are no effective cures. Significant efforts have been devoted to developing new drugs for NDs in recent years, and some small molecul...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.11.001
更新日期：2019-02-01 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：: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：:Identifying the right target for drug development is a critical bottleneck in the pharmaceutical and biotech industries. The genomics revolution has shifted the problem from a scarcity of targets to a surplus of putative drug targets. As the validity of a target cannot be simply inferred from correlative data, the key...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(02)02429-7
更新日期：2002-09-15 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：:Current multiparameter optimization (MPO) strategies make use of few experimental physicochemical descriptors (i.e., solubility at physiological pH and lipophilicity in the octanol/water system). Here, we show how new trends in drug discovery (i.e., large and flexible molecules for 'difficult' targets) call for the in...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2016.11.017
更新日期：2017-06-01 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：:The choroid plexus (CP) is a highly vascularized organ located in the brain ventricles and contains a single epithelial cell layer forming the blood-cerebrospinal fluid barrier (BCSFB). This barrier is crucial for immune surveillance in health and is an underestimated gate for entry of immune cells during numerous inf...
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：:One of the most challenging problems, if not the most challenging, in drug development is not to develop drugs to treat diseases of the central nervous system (CNS), but to manage to distribute them to the CNS across the blood-brain barrier (BBB) using transvascular routes following intravenous administration. The dev...
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
