Abstract：
:Patients can mount sustained immune responses to protein therapeutics with the production of neutralizing antibodies (NAbs) that can compromise efficacy or safety of these drugs. Dendritic cells (DCs) are required for immunoglobulin (Ig) isotype switching and the production of IgG, a process involving presentation of MHC class II binding epitopes to helper T cells (CD4+ T cells) and subsequent B cell activation. DCs, CD4+ T cells and MHC class II binding epitopes are also involved in self-tolerance. While many assay formats are available for reliable antibody detection, the complex in vivo interplay between immunogenicity and tolerance hinders accurate pre-clinical predictions of protein drug immunogenicity to humans.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Barbosa MD,Celis Edoi
10.1016/j.drudis.2007.06.005subject
Has Abstractpub_date
2007-08-01 00:00:00pages
674-81issue
15-16eissn
1359-6446issn
1878-5832pii
S1359-6446(07)00252-8journal_volume
12pub_type
杂志文章,评审abstract：:Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation. In moderate-to-severe COPD, long-acting bronchodilators are the basis of therapy. Inhaled long-acting β(2)-agonists (LABAs) are used for the treatment of COPD. LABAs have been in use since the 1990s enabling persistent bro...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.11.002
更新日期：2012-05-01 00:00:00
abstract：:The consensus hypothesis on coronary atherosclerosis suggests high LDL-C levels as the major cause and pursues it as the therapeutic target, explicitly assuming: (i) tunica intima of human coronaries consists of only one cell layer - endothelium, situated on a thin layer of scarcely cellular matrix; and (ii) subendoth...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.05.017
更新日期：2016-10-01 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：:Chemokine receptors control and mediate a diverse array of physiological and pathogenic processes. Many seven transmembrane (TM) G-protein-coupled receptors (GPCRs), including chemokine receptors, exist as homo- or heterodimers. Growing evidence indicates that the dimeric form is the basic functional structure of thes...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.04.004
更新日期：2008-07-01 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：:Compelling new evidence supports the idea that regulatory T cells play a major role in our immune system. Several subsets of these regulators have been identified recently. Differences in the phenotypical and functional characteristics of these subsets have immunological implications. From our growing knowledge of the...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(03)03021-6
更新日期：2004-04-01 00:00:00
abstract：:There is an urgent need for fresh approaches to the treatment of bacterial infections because of the changing patterns of infectious disease and the emergence of bacterial strains resistant to current antibiotics. Modification of the cell phenotype to sensitize bacteria to components of the hosts' immune system or to ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(02)02498-4
更新日期：2002-11-01 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：:Drug discovery and development is a highly complex process requiring the generation of very large amounts of data and information. Currently this is a largely unmet informatics challenge. The current approaches to building information and knowledge from large amounts of data has been addressed in cases where the types...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(02)02433-9
更新日期：2002-09-15 00:00:00
abstract：:The global burden of herpes simplex virus (HSV) legitimates the critical need to develop new prevention strategies, such as drugs and vaccines that are able to fight either primary HSV infections or reactivations. Moreover, the ever-growing number of patients receiving transplants increases the number of severe HSV in...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.03.003
更新日期：2016-04-01 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：:The occurrence of drug resistance in oncology accounts for treatment failure and relapse of diverse tumor types. Cancers contain cells at various stages of differentiation together with a limited number of 'cancer-initiating cells' able to self-renew and divide asymmetrically, driving tumorigenesis. Cancer-initiating ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.02.005
更新日期：2012-05-01 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：: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：: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：:The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologi...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.02.006
更新日期：2008-07-01 00:00:00
abstract：:Concerns emanating from the medical community about the safety and efficacy of biosimilars indicate an increasing distrust of the outcome of the drug regulatory process. To illustrate this, we analysed the creation of the European biosimilar regulatory framework, specifically focussing on the guidelines outlining appr...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2011.09.018
更新日期：2012-02-01 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：: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：:Lipidomics is a rapidly growing technology that can be used in biomedical research to study disease mechanisms, identify novel disease biomarkers and drug efficacy biomarkers, and reveal off-target effects. Lipidomics can also be used to elucidate the mechanism of action of different drug compounds or as readouts in M...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.09.008
更新日期：2014-02-01 00:00:00
abstract：:The cachexia syndrome, characterized by a marked weight loss, anorexia, asthenia and anaemia, is invariably associated with the growth of a tumour and leads to a malnutrition status caused by the induction of anorexia or decreased food intake. In addition, the competition for nutrients between the tumour and the host ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(03)02826-5
更新日期：2003-09-15 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(99)01410-5
更新日期：1999-11-01 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：:Quercetin is reported to have numerous pharmacological actions, including antidiabetic, anti-inflammatory and anticancer activities. The main mechanism responsible for its pharmacological activities is its ability to quench reactive oxygen species (ROS) and, hence, decrease the oxidative stress responsible for the dev...
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
abstract：:RNAs, particularly noncoding RNAs (ncRNAs), are becoming increasingly important therapeutic targets, because they are causative and antagonists of human disease. Indeed, aberrant RNA structural elements and expression deregulate biological processes. In this review, we describe methodologies to discover and optimize s...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.06.019
更新日期：2019-10-01 00:00:00
abstract：:Allosteric modulators have the potential to fine-tune protein functional activity. Therefore, the targeting of allosteric sites, as a strategy in drug design, is gaining increasing attention. Currently, it is not trivial to find and characterize new allosteric sites by experimental approaches. Alternatively, computati...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.07.012
更新日期：2014-10-01 00:00:00
abstract：:Sudden cardiac death, secondary to ventricular fibrillation (VF), remains the leading cause of death in the USA. Recent experimental and theoretical studies suggest that VF could be caused by spiral wave re-entry. The initiation and subsequent break-up of spiral waves has been linked to electrical alternans, a phenome...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(02)02567-9
更新日期：2003-02-15 00:00:00
abstract：:A rapid expansion in precision medicine founded on the potential for durable clinical benefit through matching a drug to a predictive marker used to select patients has driven the development of targeted drugs with accompanied companion diagnostics for patient selection. Oncology has been at the forefront, with the im...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.10.005
更新日期：2015-12-01 00:00:00
abstract：:Over the past three decades, statins have become the cornerstone of prevention and treatment of atherosclerotic cardiovascular and metabolic diseases. Albeit generally well tolerated, these drugs can elicit a variety of muscle-associated symptoms that represent the most important reason for treatment discontinuation. ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.09.001
更新日期：2017-01-01 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
