Abstract：
:Retinal photoreceptors continually endure stresses associated with prolonged light exposure and the metabolic demands of dark adaptation. Although healthy photoreceptors are able to withstand these stresses for several decades, the disease-affected retina functions at a reduced capacity and is at an increased risk for dysfunction. To alleviate cellular and metabolic stressors in degenerative retinal diseases, a new class of drugs that modulate the metabolic activity of the retina have been developed. A clinical candidate in this class (emixustat) has been shown to reduce retinal pathology in various animal models of human retinal disease and is currently under clinical study. Here, we describe the pharmacological properties of emixustat, its mechanisms of action, and potential for use in the treatment of specific retinal diseases.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Kubota R,Gregory J,Henry S,Mata NLdoi
10.1016/j.drudis.2019.11.013subject
Has Abstractpub_date
2020-02-01 00:00:00pages
292-304issue
2eissn
1359-6446issn
1878-5832pii
S1359-6446(19)30455-6journal_volume
25pub_type
杂志文章,评审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：: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：:In recent years, advances in tissue engineering and microfabrication technologies have enabled rapid growth in the areas of in vitro organoid development as well as organoid-on-a-chip platforms. These 3D model systems often are able to mimic human physiology more accurately than traditional 2D cultures and animal mode...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.07.003
更新日期：2016-09-01 00:00:00
abstract：:To successfully research and develop an animal pharmaceutical dosage form, a diverse array of issues covering basic medicine, pharmacology and technology must be addressed. Societal concerns regarding animal and public health, as well as the rapidly changing farming and economic environments, provide additional challe...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(02)02362-0
更新日期：2002-08-01 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：:We have broken old surviving dogmas and concepts used in computational chemistry and created an efficient in silico ADME-T pharmacological properties modeling and prediction toolbox for any xenobiotic. With the help of an innovative and pragmatic approach combining various in silico techniques, like molecular modeling...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.01.013
更新日期：2009-04-01 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：:New precompetitive ways of working in the pharmaceutical industry are driving the development of new informatics systems to enable their execution and management. The European Lead Factory (ELF) is a precompetitive, 30-partner collaboration between academic groups, small-medium enterprises and pharmaceutical companies...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.11.005
更新日期：2016-01-01 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：:There is a continuing need to hasten and improve protein-ligand docking to facilitate the next generation of drug discovery. As the drug-like chemical space reaches into the billions of molecules, increasingly powerful computer systems are required to probe, as well as tackle, the software engineering challenges neede...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.06.023
更新日期：2016-10-01 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：:With a productivity gap in pharmaceutical research and development, and increased industrialization in both areas, an increased need for precise indicators of productivity has emerged. Measuring scientists' performance can impact the way the tasks are performed and the level of motivation of an individual. This is a c...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2008.06.015
更新日期：2008-11-01 00:00:00
abstract：:Metabolic determinations are an integral part of every drug-discovery and drug-development program. Recent emphasis has been to increase sample throughput while, at the same time, increase information content within assays. To this end, screening for potential drug-drug interactions, overall metabolic stability and me...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.01.007
更新日期：2007-03-01 00:00:00
abstract：:Some enzymes catalyze the modification of an ensemble of substrates in vivo and, as a consequence, are not ideal targets for active-site-directed drugs. One solution to inhibiting such multisubstrate enzymes would be a drug that binds tightly to only one substrate, which prevents the binding of that substrate to the e...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.07.011
更新日期：2006-09-01 00:00:00
abstract：:Although the 5-hydroxytryptamine(6) (5-HT(6)) receptor was discovered only recently, its almost exclusive distribution in the brain makes it a promising, novel, target for central nervous system (CNS)-mediated diseases such as Alzheimer's disease (cognitive function), schizophrenia, anxiety and obesity. In the past fe...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.02.004
更新日期：2006-04-01 00:00:00
abstract：:The fact that pharmacokinetic (PK) properties of drugs influence their interaction with protein targets is a principle known for decades. The same cannot be said for the opposite, namely that targets influence the PK properties of drugs. Evidence confirming this possibility is introduced here for the first time, as we...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.09.021
更新日期：2019-12-01 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：: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：: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：:DNA methylation is an epigenetic change that results in the addition of a methyl group at the carbon-5 position of cytosine residues. The process is mediated by DNA methyltransferases (DNMTs), a family of enzymes for which inhibition is a promising strategy for the treatment of cancer and other diseases. Here, we revi...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.02.003
更新日期：2011-05-01 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：:The growing application of nanomaterials in healthcare products (i.e., cosmetics, medical devices, and medicinal products) has encouraged the upgrade of the regulatory framework within the European Community to better control their use and manage the risk of negative effects on human health and environment. Unfortunat...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.01.016
更新日期：2017-06-01 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：: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：:Immunoinformatics has recently emerged as a critical field for accelerating immunology research. Although still an evolving process, computational models now play instrumental roles, not only in directing the selection of key experiments, but also in the formulation of new testable hypotheses through detailed analysis...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.04.001
更新日期：2009-07-01 00:00:00
abstract：:A quantitative analysis has cast doubt over the limited advantages provided by particles for nose-to-brain (NTB) drug delivery. Thus, it is imperative to identify the role of nanovehicles in NTB drug delivery. If nanocarriers are used merely as an option to improve various properties of the drugs or the formulations, ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.01.005
更新日期：2018-05-01 00:00:00
abstract：:This review provides an update on the promises and pitfalls when using in vitro bioassays to evaluate beneficial and adverse health effects of botanicals and botanical preparations. Important issues addressed in the paper are: (i) the type of assays and biological effects available; (ii) false-positives, false-negativ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.05.002
更新日期：2017-08-01 00:00:00
abstract：:Stimulation of bone regeneration using growth factors is a promising approach for musculoskeletal regenerative engineering. However, common limitations with protein growth factors, such as high manufacturing costs, protein instability, contamination issues, and unwanted immunogenic responses of the host reduce potenti...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.01.012
更新日期：2014-06-01 00:00:00
abstract：:The lack of structural information on hepatitis C virus (HCV) surface proteins has so far hampered the development of effective vaccines. Recently, two crystallographic structures have described the core portion (E2c) of E2 surface glycoprotein, the primary mediator of HCV entry. Despite the importance of these studie...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.08.011
更新日期：2014-12-01 00:00:00
abstract：:'The climate is perfect for a proactive search for partners between industry and academia.' ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(00)01543-9
更新日期：2000-09-01 00:00:00
