Abstract：
:Understanding skin metabolism is important when considering drug discovery and safety assessment. This review compares xenobiotic skin metabolism in ex vivo skin to reconstructed human skin and reconstructed human epidermis models, concentrating on phase I and phase II enzymes. Reports on phase I enzymes are more abundant than for phase II enzymes with mRNA and protein expression far more reported than enzyme activity. Almost all of the xenobiotic metabolizing enzymes detected in human skin are also present in liver. However, in general the relative levels are lower in skin than in liver and fewer enzymes are reported.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Kazem S,Linssen EC,Gibbs Sdoi
10.1016/j.drudis.2019.06.002subject
Has Abstractpub_date
2019-09-01 00:00:00pages
1899-1910issue
9eissn
1359-6446issn
1878-5832pii
S1359-6446(18)30219-8journal_volume
24pub_type
杂志文章,评审abstract：:Senescence forms a universal block to tumorigenesis which impacts on all hallmarks of cancer, making it an attractive target for drug discovery. Therefore a strategy must be devised to focus this broad potential into a manageable drug discovery programme. Several issues remain to be addressed including the lack of rob...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.01.019
更新日期：2012-03-01 00:00:00
abstract：:Outnumbering our own cells over ten times, gut microbes can even be considered an additional organ. Several studies have explored the association between microbiomes and antitumor drug response. It has been reported that the presence of specific bacteria might modulate cancer progression and the efficacy of anticancer...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.02.009
更新日期：2019-04-01 00:00:00
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
更新日期：2011-05-01 00:00:00
abstract：:The Science for Life Laboratory Drug Discovery and Development (SciLifeLab DDD) platform reaches out to Swedish academia with an industry-standard infrastructure for academic drug discovery, supported by earmarked funds from the Swedish government. In this review, we describe the build-up and operation of the platform...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.06.026
更新日期：2016-10-01 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：: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：:We analyzed a list of the top 100 bestselling drugs as a struggling market for new FDA approvals. Using the time from drug approval by the FDA as a measure of drug age, our analysis showed that the top 100 bestselling drugs are getting older. This reflects the stalled launch of new drugs into the market during recent ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2015.06.015
更新日期：2015-11-01 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：:Atomic force microscopy is being used ever more widely in biological imaging, because of its unique ability to provide structural information at the single molecule level and under near-physiological conditions. Detailed topographic images of potential drug targets, such as proteins and DNA, have been produced, and th...
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：: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：:The clinical advancement of HIV-1 attachment inhibitors was hindered initially by poor bioavailability. Attempts to identify improved candidates revealed that solubility and dissolution-rate-limited absorption are barriers to achieving adequate antiviral plasma levels. This was mitigated by forming nanosized drugs or ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2014.03.025
更新日期：2014-09-01 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：: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：:For several decades, the pharmaceutical industry has suffered due to major issues such as reductions of the number of FDA approved drugs and biologics. Several analyses have been highlighted that the 'druglikeness' is one of the strategies to improve succeed rates of screening such as, for instance, high-throughput sc...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.01.005
更新日期：2016-04-01 00:00:00
abstract：:In the last ten years, public online databases have rapidly become trusted valuable resources upon which researchers rely for their chemical structures and data for use in cheminformatics, bioinformatics, systems biology, translational medicine and now drug repositioning or repurposing efforts. Their utility depends o...
journal_title：Drug discovery today
pub_type： 社论
doi：10.1016/j.drudis.2011.07.007
更新日期：2011-09-01 00:00:00
abstract：:There is a continuous demand for preclinical modeling of the interaction of dendritic cells with the immune system and cancer cells. Recent progress in gene expression profiling with nucleic acid microarrays, in silico modeling and in vivo cell and animal approaches for non-clinical proof of safety and efficacy of the...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.07.010
更新日期：2013-01-01 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：: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：:Atrial fibrillation (AF) is the most common cardiac arrhythmia facing physicians, afflicting 13% of men and 11% of women over 85 years of age. Epidemiological studies estimate that there are ≥ 11 million AF sufferers in the seven major economies and that its prevalence will increase two- to threefold over the next 50 ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.02.007
更新日期：2012-07-01 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：:Indacaterol/glycopyrronium (IND/GLY) 110/50mcg was the first once-daily, long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combination (FDC) approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD). Development of IND/GLY was driven by the need to improve the...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.10.015
更新日期：2018-01-01 00:00:00
abstract：:Over the past decade, together with the improvement of traditional cancer treatments, conveniently designed (with respect to their size, shape, main material, and coating) and specifically targeted nanovehicles have been developed. Nano-sized carriers can be functionalized to recognize key structures expressed in canc...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.06.020
更新日期：2014-10-01 00:00:00
abstract：:Translating academic medical research into new therapies is an important challenge for the biopharmaceutical industry and investment communities, which have historically favored later-stage assets with lower risk and clearer commercial value. The Stanford SPARK program is an innovative model for addressing this challe...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.03.015
更新日期：2017-07-01 00:00:00
abstract：:The development of any stem-cell-based therapy (and a potential one for deafness is no exception) relies on the generation of the necessary tools: 'cell drugs' that can be safely manufactured for their clinical application. An increasing body of work has focussed on the identification, in animal models, of potential s...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2010.02.006
更新日期：2010-04-01 00:00:00
abstract：:Our understanding of the detailed recognition and processing of clinically useful therapeutic agents has grown rapidly in recent years, and we are now able to begin to apply this knowledge to the rational treatment of disease. Mammalian carboxylesterases (CEs) are enzymes with broad substrate specificities that have k...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03383-0
更新日期：2005-03-01 00:00:00
abstract：:Magnetic nanoparticles (MNPs) play a vital role for improved imaging applications. Recently, a number of studies demonstrate MNPs can be applied for targeted delivery, sustained release of therapeutics, and hyperthermia. Based on stable particle size and shape, biocompatibility, and inherent contrast enhancement chara...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.04.018
更新日期：2017-08-01 00:00:00
abstract：:Nonclinical safety testing of new biotherapeutic entities represents its own challenges and opportunities in drug development. Hot topics in this field have been discussed recently at the 2nd Annual BioSafe European General Membership Meeting. In this feature article, discussions on the challenges surrounding the use ...
journal_title：Drug discovery today
pub_type：
doi：10.1016/j.drudis.2013.08.003
更新日期：2013-12-01 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：:Medicinal chemistry makes a vital contribution to small molecule drug discovery, and the quality of it contributes directly to research effectiveness as well as to downstream costs, speed and survival in development. In recent years, the discipline of medicinal chemistry has evolved and witnessed many noteworthy contr...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2012.01.010
更新日期：2012-06-01 00:00:00
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 ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.06.005
更新日期：2007-08-01 00:00:00
