Abstract：
:Nonalcoholic steatohepatitis (NASH) is emerging as a major public health issue for the 21st century and is associated with significant liver-related morbidity and mortality. At present, there are no approved drug therapies for NASH. Consequently, NASH has become the focus of significant public and private research and development. In this review, we highlight the research and development (R&D) challenges and opportunities in this emerging therapeutic area. In particular, we consider the impact of the development of new biomarker strategies on clinical trial execution and design, and the positioning of single and combination therapies in future approaches to the treatment of NASH.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Black D,Brockbank S,Cruwys S,Goldenstein K,Hein P,Humphries Bdoi
10.1016/j.drudis.2018.09.020subject
Has Abstractpub_date
2019-02-01 00:00:00pages
560-566issue
2eissn
1359-6446issn
1878-5832pii
S1359-6446(18)30119-3journal_volume
24pub_type
杂志文章,评审abstract：:2018 was a remarkable year, both in terms of the number of new molecular entities (NMEs) approved and the organizations developing them. In total, 59 NMEs received a nod from the US Food and Drug Administration (FDA), most of which were approved using a priority or breakthrough designation. Orphan drugs accounted for ...
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
abstract：:With the aging of the general population, there is an increasing need for bone defect repair, prompting the development of reliable alternatives to autologous bone grafting, without the usually associated major drawbacks (i.e., limited volume and severe postoperative pain). Given the crucial role that miRNAs appear to...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.04.007
更新日期：2017-07-01 00:00:00
abstract：:The concept of drug-likeness helps to optimise pharmacokinetic and pharmaceutical properties, for example, solubility, chemical stability, bioavailability and distribution profile. A number of molecular descriptors have emerged as reasonably informative and predictive, for example, the Rule-of-Five. Here, we review so...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.11.007
更新日期：2008-04-01 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：:Of the three viral enzymes essential to HIV replication, HIV-1 integrase (IN) is gaining popularity as a target for the antiviral therapy of AIDS. Substantial work focusing on IN has been done over the past three decades, which has facilitated and led to the approval of three drugs. Here, we discuss in detail the deve...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.07.012
更新日期：2015-11-01 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：: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 f...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.01.012
更新日期：2012-06-01 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 endocannabinoid system is implicated in, and regulates, several physiological processes, ranging from food intake and energy balance to pain and inflammation. 2-Arachidonoylglycerol (2-AG) is a full agonist at the cannabinoid receptors which classically mediate its effects. The activity of this bioactive lipid is ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.07.009
更新日期：2014-03-01 00:00:00
abstract：:Immunotherapies have changed the treatment strategy of some types of tumor including melanoma and, more recently, non-small-cell lung cancer (NSCLC). Immune checkpoints are crucial for the maintenance of self-tolerance and it is known that some tumors use checkpoint systems to evade antitumor immune response. The trea...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.05.016
更新日期：2017-08-01 00:00:00
abstract：:'Many professional scientists over the years have expressed their thoughts and ideas in poetry.' ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(00)01556-7
更新日期：2000-10-01 00:00:00
abstract：:Micro RNAs (miRNAs) are a class of naturally occurring ∼ 22 nt long non-coding small RNA molecules that regulate the expression of a wide range of genes involved in development, growth, proliferation and apoptosis. miRNAs are evolutionarily conserved from plants to animals, and they regulate and fine-tune a diverse ar...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2010.07.003
更新日期：2010-09-01 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：:Proteomic-based techniques provide a powerful tool for identifying the full spectrum of protein targets of a drug, elucidating its mechanism(s) of action, and identifying biomarkers of its efficacy and safety. Herein, we outline the technological advancements in the field, and illustrate the contribution of proteomics...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.03.001
更新日期：2017-06-01 00:00:00
abstract：:Medical oncologists are increasingly using anti-angiogenic drugs, but identifying the best-suited drug and the optimal dosage and schedule for treatment of patients remain challenging issues. Circulating endothelial cells (CECs) and circulating endothelial progenitors (CEPs) are modulated in a variety of diseases incl...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.08.011
更新日期：2007-10-01 00:00:00
abstract：:The inhaled delivery of nanomedicines has attracted much attention in the treatment of lung diseases or systemic diseases. However, there is a lack of understanding about their fate upon lung delivery. Thus, the objective of this review is to summarize physicochemical properties affecting the fate of nanoparticles aft...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.09.023
更新日期：2020-01-01 00:00:00
abstract：:Inhibitors of epigenetic targets have entered clinical trials with some success, in particular for combined therapies. Like many other chemotherapeutics these new classes of molecules have dose-limiting toxicities and highly active metabolism in vivo resulting in lower efficacy than expected. This review presents drug...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.03.017
更新日期：2014-09-01 00:00:00
abstract：:Spinal cord infarction (SCI) is a rare but disabling disorder caused by a wide spectrum of conditions. Given the lack of randomized-controlled trials, contemporary treatment concepts are adapted from guidelines for cerebral ischemia, atherosclerotic vascular disease, and acute traumatic spinal cord injury. In addition...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.06.015
更新日期：2016-10-01 00:00:00
abstract：:The use of computational filters for excluding supposedly nonspecific and promiscuous compounds from chemical libraries is a controversial issue, because many drugs used in clinics today would never reach the market if these filters were applied. In part, this conflict could be caused by the paradigm: one-drug-one-tar...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2016.02.004
更新日期：2016-06-01 00:00:00
abstract：:The Discussion Forum provides a medium for airing your views on any issues related to the pharmaceutical industry and obtaining feedback and discussion on these views from others in the field. You can discuss issues that get you hot under the collar, practical problems at the bench, recently published literature, or j...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(01)01816-5
更新日期：2001-06-01 00:00:00
abstract：:Angiogenesis is an exquisitely regulated process that is required for physiological processes and is also important in numerous diseases. Tumors utilize angiogenesis to generate the vascular network needed to supply the cancer cells with nutrients and oxygen, and many cancer drugs aim to inhibit tumor angiogenesis. An...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.09.026
更新日期：2015-02-01 00:00:00
abstract：:Drug discovery has historically advanced by synergy and chance. These are proving insufficient to meet the needs of the marketplace and the demands of modern medicine. We describe our strategic approaches to building and employing flexible informatics tools to transform and improve the workflows and efficiencies of th...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(04)03277-5
更新日期：2005-01-01 00:00:00
abstract：:Novel starting points for drug discovery projects are generally found either by screening large collections of compounds or smaller more-focused libraries. Ideally, hundreds or even thousands of actives are initially found, and these need to be reduced to a handful of promising lead series. In several sequential steps...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03703-7
更新日期：2006-01-01 00:00:00
abstract：:When cross-reactivity of a lead antibody across species is limited, antibody development programs require the generation of surrogate molecules or surrogate animal models necessary for the conduct of preclinical pharmacology and safety studies. When surrogate approaches are employed, the complexities and challenges fo...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.09.014
更新日期：2009-12-01 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：:The biopharmaceutical industry is characterized by intense competition, high uncertainty, and strong dependence on scientific knowledge. We show that in order to succeed in this industry, firms need to be positioned along three strategic dimensions: the level of inter-firm R&D partnering, the level of diversification,...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2009.04.004
更新日期：2009-08-01 00:00:00
abstract：:The blood-brain barrier (BBB) hinders the accumulation of active compounds in the central nervous system, thus decreasing their therapeutic effectiveness. To overcome this obstacle, interesting supramolecular nanodevices are herein considered. These systems have many advantages over the conventional formulations, such...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.02.006
更新日期：2011-04-01 00:00:00
abstract：:Treatment of neurodegenerative diseases, such as Alzheimer's disease, multiple sclerosis, Parkinson's disease and amyotrophic lateral sclerosis (ALS), represents a major challenge for the pharmaceutical industry. These disorders have common and unique molecular pathological characteristics that result in serious reduc...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359644602025400
更新日期：2003-01-01 00:00:00
abstract：:Pancreatic cancer is one of the most aggressive and lethal human malignancies. Drug therapies and radiotherapy are used for treatment as adjuvants to surgery, but outcomes remain disappointing. Advances in tissue engineering suggest that 3D cultures can reflect the in vivo tumor microenvironment and can guarantee a ph...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.01.012
更新日期：2017-04-01 00:00:00
abstract：:Carcinomas overexpressing EGFR family receptors are of high clinical importance, because the receptors have prognostic value and are used as molecular targets for anticancer therapy. Insufficient drug efficacy necessitates further in-depth research of the receptor biology and improvement in preclinical stages of drug ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.09.003
更新日期：2019-01-01 00:00:00
