Abstract:
:Kidneys have a major role in normal physiology and metabolic homeostasis. Loss or impairment of kidney function is a common occurrence in several metabolic disorders, including hypertension and diabetes. Chronic kidney disease (CKD) affect nearly 10% of the population worldwide; ranks 18th in the list of causes of death; and contributes to a significant proportion of healthcare costs. The tissue repair and regenerative potential of kidneys are limited and they decline during aging. Recent studies have demonstrated a key role for epigenetic processes and players, such as DNA methylation, histone modifications, noncoding (nc)RNA, and so on, in both kidney development and disease. In this review, we highlight these recent findings with an emphasis on aberrant epigenetic changes that accompany renal diseases, key targets, and their therapeutic value.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Kota SK,Kota SBdoi
10.1016/j.drudis.2017.04.020subject
Has Abstractpub_date
2017-07-01 00:00:00pages
1112-1122issue
7eissn
1359-6446issn
1878-5832pii
S1359-6446(17)30239-8journal_volume
22pub_type
杂志文章,评审abstract::Drug-delivery technologies for modified drug release have been in existence for decades, but their utilization has been largely limited to post-launch efforts improving therapeutic outcomes. Recently, they have gained renewed importance because the pharmaceutical industry is steadily shifting to a more integrated disc...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.12.008
更新日期:2020-12-14 00:00:00
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...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.11.013
更新日期:2020-02-01 00:00:00
abstract::Neuropathic pain research remains a challenging undertaking owing to: (i) the lack of understanding about the underlying disease processes; and (ii) poor predictive validity of the current models of evoked pain used for the screening of novel compounds. Common consensus is that experimental models replicate symptoms (...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.02.010
更新日期:2012-08-01 00:00:00
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...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.09.020
更新日期:2019-02-01 00:00:00
abstract::The pharmacological and adverse effect profiles of the two approved therapies for IPF make the development of new therapies challenging. Considering the similarity of the characteristics of drug candidates to Standard of Care is important in defining positioning and development strategies for this disease. ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.09.019
更新日期:2020-12-01 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::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::Drug-induced liver injury (DILI) is a leading cause of drugs failing during clinical trials and being withdrawn from the market. Comparative analysis of drugs based on their DILI potential is an effective approach to discover key DILI mechanisms and risk factors. However, assessing the DILI potential of a drug is a ch...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2011.05.007
更新日期:2011-08-01 00:00:00
abstract::The tumor vasculature transports oxygen, nutrients and drugs for crucial roles in tumor therapy. Antivascular therapy directly targets existing tumor vessels to reduce blood perfusion and then inhibit tumor growth. Vascular disrupting agents and ultrasound-stimulated microbubble destruction use chemical toxicity and p...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.06.001
更新日期:2017-10-01 00:00:00
abstract::One of the world's fastest growing cities, Atlanta is the business center of the Southeast U.S. and is rapidly becoming a leader for biotechnology innovation. ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/S1359-6446(05)03374-X
更新日期:2005-02-15 00:00:00
abstract::In this paper, we review the key solutions that enabled evolution of the lead optimization screening support process at Bristol-Myers Squibb (BMS) between 2004 and 2009. During this time, technology infrastructure investment and scientific expertise integration laid the foundations to build and tailor lead optimizatio...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.02.012
更新日期:2012-07-01 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 recent years, there have been significant developments made in the way new drugs are being discovered and developed. Such changes are driven by new technologies that have expanded the opportunities to prepare and screen large libraries of compounds in a rapid time frame by the use of high-throughput synthesis and s...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(04)03298-2
更新日期:2005-01-15 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::Here, we detail the major developments in methods and techniques that are applicable to high-throughput synthesis that have evolved over the past five years, with an emphasis on the combination of microwave-based synthesis with techniques such as polymer-assisted purification and immobilized reagents and catalysts. Ot...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2007.04.004
更新日期:2007-06-01 00:00:00
abstract::Proline-rich Akt substrate 40kDa (PRAS40) bridges cell signaling between protein kinase B (Akt) and the mammalian target of rapamycin complex 1 (mTORC1). Both Akt and mTORC1 can phosphorylate PRAS40. As a negative regulator of mTORC1, PRAS40 prevents the binding of mTOR to its substrates. The phosphorylation of PRAS40...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.04.005
更新日期:2016-08-01 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::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::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::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::Application of humanized xenotransplantation disease models and experimental clinical studies in the context of translational research in drug discovery in dermatology is an opportunity to reduce failure due to lack of efficacy in clinical development stage. ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2007.10.009
更新日期:2008-03-01 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::The function of many key proteins and transcription factors involved in cell growth can be regulated by their cellular localization. Such proteins include the tumor suppressor p53 and the nuclear factor kappaB. Although the idea of trapping such proteins in either the nucleus or cytoplasm has been introduced as a pote...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(02)02562-x
更新日期:2003-01-15 00:00:00
abstract::For many years, there has been spirited debate as to the relative importance of environmental and genetic factors in the pathogenesis of cancer. Current efforts to annotate the human genome for germ-line genetic variants should establish the foundation for dissecting the contribution of genetics to the risk for cancer...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(04)03179-4
更新日期:2004-07-15 00:00:00
abstract::Long-acting drug nanosuspension formulations are coming to the fore as controlled release strategies for several medical conditions and as a preventative measure against HIV infection. However, such delivery systems must, by necessity, be given by hypodermic injection, typically into muscle. This poses problems for pa...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.10.013
更新日期:2018-05-01 00:00:00
abstract::SNPs can alter protein function and phenotype, leading to altered pharmacogenomic drug profiles. The exponential number of SNPs makes it impossible to perform wet laboratory experiments to determine the biological significance of each one. However, bioinformatics tools can be used to screen for potentially deleterious...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2011.07.005
更新日期:2011-09-01 00:00:00
abstract::Here, we describe a novel workflow combining informatic and experimental approaches to enable evidence-based prioritising of targets from large sets in parallel. High-throughput protein production and biophysical fragment screening is used to identify those targets that are tractable and ligandable. As proof of concep...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.09.003
更新日期:2020-09-10 00:00:00
abstract::The proces of piecemeal microautophagy of the nucleus describes the way in which autophagy occurs in the nucleus, a realm of the cell once considered to be off limits for autophagy. ...
journal_title:Drug discovery today
pub_type: 新闻
doi:10.1016/s1359-6446(03)02636-9
更新日期:2003-03-15 00:00:00
abstract::There is currently a marketed drug for nearly every nuclear receptor for which the natural ligand has been identified. However, because of the complexity of signal transduction by this class of ligand-regulated transcription factors, few of these drugs have been optimized for pharmaceutical effectiveness. Over the pas...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(04)03201-5
更新日期:2004-09-01 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