Abstract:
:Statins are an established therapeutic modality for the treatment of hypercholesterolemia. Although they generally exhibit a good efficacy and tolerability profile, their reputation has been tarnished as a result of reports of myotoxicity and, more recently, observations of proteinuria. The increased incidence of proteinuria with rosuvastatin was of particular concern, and raised questions about the renoprotective actions of statins. Different hypotheses have been put forward to explain the mechanisms of statin-induced proteinuria. The multifarious effects of statins, independent of their effects on cholesterol-lowering, form the basis of such hypotheses. However, rosuvastatin-associated proteinuria is transient and reversible and even at the highest dose did not affect renal function after prolonged treatment. It would appear that clinically relevant proteinuria is not associated solely with rosuvastatin and might represent a minor class effect of statins with a fairly low incidence. However, definitive proof of this assertion will need to be provided by rigorous testing.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Tiwari Adoi
10.1016/j.drudis.2006.03.017subject
Has Abstractpub_date
2006-05-01 00:00:00pages
458-64issue
9-10eissn
1359-6446issn
1878-5832pii
S1359-6446(06)00061-4journal_volume
11pub_type
杂志文章,评审abstract::Advanced chemotherapy fails to treat liver cancer but recent progress in understanding epigenetic modifications have witnessed promising clinical outcomes. Epigenetic alteration is the alteration of epigenomes (surrounding histone proteins) without changing the DNA sequence. Such epigenetic mechanisms include histone ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.07.008
更新日期:2017-11-01 00:00:00
abstract::Since the introduction of cisplatin in cancer therapy, metal complexes and organometallic compounds have been gaining growing importance in oncology. The impressive clinical effectiveness of cisplatin is limited by significant side effects and the emergence of drug resistance. Thus, novel classic and unconventional Pt...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.02.002
更新日期:2009-05-01 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::The energy substrate preference of the human heart is well regulated and is modified upon aging, in that the fetal heart uses glucose, whereas the adult heart utilizes fatty acids. Various human and animal studies suggest a shift in myocardial substrate utilization and decreased rate of myocardial fatty acid uptake an...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.02.010
更新日期:2016-06-01 00:00:00
abstract::In recent years there has been a dramatic increase in the number of freely accessible online databases serving the chemistry community. The internet provides chemistry data that can be used for data-mining, for computer models, and integration into systems to aid drug discovery. There is however a responsibility to en...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.02.013
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(00)01619-6
更新日期:2001-02-01 00:00:00
abstract::This review illustrates notable recent progress in the field of medicinal bioinorganic chemistry as many new approaches to the design of innovative metal-based anticancer drugs are emerging. Current research addressing the problems associated with platinum drugs has focused on other metal-based therapeutics that have ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.09.003
更新日期:2009-12-01 00:00:00
abstract::Tuberculosis drug discovery has shifted in recent years from a primarily target-based approach to one that uses phenotypic high-throughput screens. As examples of this, through our EU-funded FP7 collaborations, New Medicines for Tuberculosis was target-based and our more-recent More Medicines for Tuberculosis project ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.09.025
更新日期:2017-03-01 00:00:00
abstract::The US Food and Drug Administration (FDA) Expanded Access (EA) Program, which allows for compassionate uses of unapproved therapeutics and diagnostics outside of clinical trials, has gained significant traction during the Coronavirus 2019 (COVID-19) pandemic. While development of vaccines has been the major focus, unc...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.11.025
更新日期:2020-11-27 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::A fierce dispute has arisen between the supporters of phenotypic and target-focused screening regarding which path grants the higher probability of successful drug development. A chance to reconcile these two approaches lies in successful target deconvolution (TD) after phenotypic screens. But, despite the panoply of ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.10.009
更新日期:2019-02-01 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::Bispecific antibodies (bsAbs) combine specificities of two antibodies and simultaneously address different antigens or epitopes. BsAbs with 'two-target' functionality can interfere with multiple surface receptors or ligands associated, for example with cancer, proliferation or inflammatory processes. BsAbs can also pl...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2015.02.008
更新日期:2015-07-01 00:00:00
abstract::Drug therapy for the treatment of tumors is often limited by a narrow therapeutic index. One approach that overcomes this limitation is the active targeting of tumors with particulate drug carriers. The derivatization of particulate drug carriers with a ligand leads to the selective targeting of the particulate to sel...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(03)02988-X
更新日期:2004-03-01 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::Effective cancer treatment remains a significant challenge in human healthcare. Although many different types of cancer therapy have been tested, scientists have now concluded that combinations of drugs, or drugs plus gene therapy, can target multiple pathways to fight cancer. Nanovehicles can increase drug uptake ins...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.06.027
更新日期:2020-08-01 00:00:00
abstract::Although the oral route is the most popular and acceptable way of drug administration owing to good patient compliance and safety, oral drug delivery is faced with continuous challenges regarding poorly soluble, poorly permeable or gastrointestinally unstable drugs such as proteins and polypeptides. The overall bioava...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.03.001
更新日期:2014-07-01 00:00:00
abstract::Oral delivery of peptides and proteins remains an attractive alternative to parenteral delivery and has challenged various attempts at delivery development. Incorporation of new tools into the delivery systems that can raise membrane permeability of macromolecules is essential to attain high oral bioavailability that ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2006.08.005
更新日期:2006-10-01 00:00:00
abstract::The development of tissue-engineering (TE) solutions for osteochondral (OC) regeneration has been slowed by technical hurdles related to the recapitulation of their complex and hierarchical architecture. OC defects refer to damage of both the articular cartilage and the underlying subchondral bone. To repair an OC tis...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.01.008
更新日期:2018-03-01 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::Drug discovery is shifting focus from industry to outside partners and, in the process, creating new bottlenecks. Technologies like high throughput screening (HTS) have moved to a larger number of academic and institutional laboratories in the USA, with little coordination or consideration of the outputs and creating ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2012.10.007
更新日期:2013-03-01 00:00:00
abstract::During the past 10 years, substantial progress has been made in the discovery and development of small molecule glutamate carboxypeptidase II (GCP II) inhibitors. These inhibitors have provided the necessary tools to investigate the physiological role of GCP II as well as the potential therapeutic benefits of its inhi...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2007.07.010
更新日期:2007-09-01 00:00:00
abstract::Total-body exposure to ionizing radiation (TBI) results in life-threatening acute radiation syndrome (ARS), which encompasses hematopoietic and gastrointestinal (GI) injuries and results in dose-dependent morbidity and mortality. Management of ARS warrants the deployment of effective medical countermeasure agents (MCM...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.02.004
更新日期:2020-04-01 00:00:00
abstract::Opinions about the therapeutic efficacy of medicinal herbs differ significantly. Some reported herbal efficacies at low doses of active ingredients suggest a need for investigating whether these are because of placebo or multi-ingredient synergistic effects. This review discusses the opinions, methods and outcomes of ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.03.012
更新日期:2009-06-01 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::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::Adverse environmental conditions faced by an individual early during its life, such as gestational hypoxia, can have a profound influence on the risk of diseases, such as neurological disorders, in later life. Clinical and preclinical studies suggest that epigenetic programming of gene expression patterns in response ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.09.010
更新日期:2014-12-01 00:00:00
abstract::Identifying new indications for existing drugs creates new therapeutic options while bypassing much of the costs and time involved with bringing a new drug to market. The rediscovery of a generic drug, however, is a challenging pursuit because there is no formal regulatory approach and a lack of economic interest by p...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2017.08.008
更新日期:2018-01-01 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::Drug delivery systems are undergoing technology changes to enhance patient comfort and compliance. Electronic drug delivery (E-drug delivery) systems are being developed to regulate drug dose delivery by easy monitoring of doses, especially in chronic and age-related diseases. E-drug delivery can monitor the correct d...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.02.005
更新日期:2019-04-01 00:00:00