Abstract:
:The human ether-a-go-go-related gene (hERG) encodes the pore-forming alpha-subunit of a voltage-gated potassium (K(+)) channel. A variety of unrelated compounds reduce K(+ )current in the heart by blocking the pore or disrupting trafficking of the hERG channel to the membrane surface. This induces a syndrome known as long QT, which arises from abnormalities in action potential repolarisation and can degenerate into lethal cardiac arrhythmias. As a result, this undesirable side effect has severely hindered safe drug development. This review describes progress in understanding the molecular basis for drug binding to hERG, outlines the characteristics of hERG ligands and discusses experimental and in silico approaches for identifying compounds with QT liabilities. Recent developments should enable recognition of hERG-positive compounds at the early stages of their development.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Stansfeld PJ,Sutcliffe MJ,Mitcheson JSdoi
10.1517/17425255.2.1.81subject
Has Abstractpub_date
2006-02-01 00:00:00pages
81-94issue
1eissn
1742-5255issn
1744-7607journal_volume
2pub_type
杂志文章,评审abstract::Acute kidney injury is a common condition and is associated with a high mortality rate. It has been recognised that routinely used measures of renal function, such as levels of blood urea nitrogen and serum creatinine, increase significantly only after substantial kidney injury occurs and then with a time delay. Insen...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2.5.697
更新日期:2006-10-01 00:00:00
abstract:INTRODUCTION:Small molecule tyrosine and serine-threonine kinase inhibitors (TKIs and STKIs) are emerging drugs that interfere with downstream signaling pathways involved in cancer proliferation, invasion, metastasis and angiogenesis. The understanding of their pharmacokinetics, the identification of their transporters...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1006626
更新日期:2015-05-01 00:00:00
abstract:INTRODUCTION:Therapeutic hypothermia is being employed clinically due to its neuro-protective benefits. Both critical illness and therapeutic hypothermia significantly affect drug disposition, potentially contributing to drug-therapy and drug-disease interactions. Currently, there is limited information on the known al...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.574127
更新日期:2011-07-01 00:00:00
abstract:INTRODUCTION:Chronic constipation is a frequent condition often treated pharmacologically. The laxatives available belong to very different pharmacologic groups. AREAS COVERED:This is a short but comprehensive review of the pharmacology, efficacy and safety of currently available laxatives for chronic constipation. Pe...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.773972
更新日期:2013-04-01 00:00:00
abstract:INTRODUCTION:Enzalutamide is the first approved second-generation androgen receptor (AR) antagonist in the treatment of metastatic castration-resistant prostate cancer (mCRPC) with or without docetaxel-based chemotherapy. Over the past 5 years, a number of attempts were made to determine the efficacy of enzalutamide in...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2018.1440288
更新日期:2018-03-01 00:00:00
abstract::Toxicogenomics is the application of gene expression profiling technology to toxicology. This results in the generation of very large and complex gene expression data sets associated with the development of toxicities. It is widely assumed that this data can be deconvoluted to reveal novel insights into toxicological ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.1.2.247
更新日期:2005-08-01 00:00:00
abstract:INTRODUCTION:Whereas in the past, (Q)SAR methods have been largely used to support the design of new drugs, in the last few decades, there has been a new interest in its applications for the assessment of drug safety. In particular, the ICH M7 guideline has introduced the concept that (Q)SAR predictions for the Ames mu...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2020.1785428
更新日期:2020-08-01 00:00:00
abstract:INTRODUCTION:Oral mucositis, one of the major side effects of chemotherapy and irradiation, is still a burden of modern oncology. The keratinocyte growth factor (KGF) palifermin has been approved as a new, targeted therapy for the prevention of severe oral mucositis. AREAS COVERED:The authors review the literature on ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.566556
更新日期:2011-04-01 00:00:00
abstract::Luminogenic cytochrome P450 (CYP) assays couple CYP enzyme activity to firefly luciferase luminescence in a technology called P450-Glo(TM) (Promega). Luminogenic substrates are used in assays of human CYP1A1, -1A2, -1B1, -2C8, -2C9, -2C19, -2D6, -2J2, -3A4, -3A7, -4A11, -4F3B, -4F12 and -19. The assays detect dose-dep...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2.4.629
更新日期:2006-08-01 00:00:00
abstract:INTRODUCTION:Chronic hepatitis C virus (HCV) infection has recently become a curable disease with antiviral therapy. The knowledge of drug interactions using direct-acting antivirals (DAA) may permit maximizing antiviral efficacy and avoiding drug-related toxicities. Ageing in the chronic hepatitis C population, along ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.998997
更新日期:2015-03-01 00:00:00
abstract::Introduction: Although the hepatotoxicity of acetaminophen is a well-known problem, the search for reliable biomarker of toxicity is still a current issue as clinical tools are missing to assess patients intoxicated following chronic use, sequential ingestion, use of modified release formulations or in case of delayed...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2019.1642323
更新日期:2019-08-01 00:00:00
abstract:INTRODUCTION:Variations in the human genome sequence sometimes play an important role in pharmacokinetics and/or pharmacodynamics. Previous studies have demonstrated a high degree of variation both between and within different ethnic populations. Areas covered: This review sought to summarize key SNPs in CYP2B6, CYP3A ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1391214
更新日期:2017-11-01 00:00:00
abstract:OBJECTIVES:A medical need remains for a once-daily insulin with 24-h basal coverage in all patients. We characterize the steady-state (SS) pharmacokinetic/pharmacodynamic properties of insulin degludec (IDeg) versus insulin glargine (IGlar). RESEARCH DESIGN AND METHODS:In this controlled, single-center study, 66 type ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,随机对照试验
doi:10.1517/17425255.2015.1058779
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Testosterone replacement therapy in hypogonadal men has been used for > 60 years. The use of testosterone substitution is continuously growing and is given to aging men to improve the quality of life. Because testosterone use is associated with muscle strength enhancing effects, it has become a popular drug ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250902976862
更新日期:2009-07-01 00:00:00
abstract:INTRODUCTION:Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of T-cell neoplasms. Most patients with PTCL have a poor outcome with conventional therapies and are not cured without stem-cell transplantation. Pralatrexate, a novel antifolate chemotherapeutic agent, was rationally designed to impede folate m...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.595404
更新日期:2011-09-01 00:00:00
abstract:INTRODUCTION:It is widely accepted that current practice of polypharmacy inevitably increases the incidence of drug-drug interactions (DDIs). Serious DDIs are a major liability for new molecular entities entering the pharmaceutical market. Various strategies are employed to avoid problematic compounds for clinical deve...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1013095
更新日期:2015-04-01 00:00:00
abstract:INTRODUCTION:DNA damaging drugs are widely used for the chemotherapeutic treatment of high-grade osteosarcoma (HGOS). In HGOS patients, several germline polymorphisms have been reported to impact on the development of adverse toxic events related to DNA damaging drugs treatment. Some of these polymorphisms, when presen...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2019.1588885
更新日期:2019-04-01 00:00:00
abstract::Introduction: In quantitative modeling, the resolving of underpredictions and overpredictions of hepatic clearance (CLh) makes a top priority for pharmacokinetic modelers. Clearly, the 'protein-mediated hepatic uptake' is a violation of 'the free drug hypothesis', but the lack of its consideration in CLh-predictive ap...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2019.1640679
更新日期:2019-08-01 00:00:00
abstract:INTRODUCTION:Hemophilia A is a bleeding disorder resulting from a lack of clotting factor VIII (FVIII), and treatment typically consists of prophylactic replacement of the deficient factor. However, high between subject variability precludes the development of a 'one size fits all' dosing strategy and necessitates an i...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2016.1214711
更新日期:2016-11-01 00:00:00
abstract:INTRODUCTION:Lenalidomide is an oral immunomodulatory drug, which was recently introduced for the treatment of multiple myeloma (MM). It has been used for the treatment of newly diagnosed and relapsed MM patients, as both maintenance and preventive therapy. Available data show a progression-free survival and overall su...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.712685
更新日期:2012-09-01 00:00:00
abstract::Introduction: The target concentration strategy uses PKPD information for dose determination. Models have also quantified exposure-response relationships, improved understanding of developmental pharmacokinetics, rationalized dose prescription, provided insight into the importance of covariate information, explained d...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2020.1739648
更新日期:2020-04-01 00:00:00
abstract:INTRODUCTION:Obesity is an epidemic associated with significant morbidity. Lorcaserin , a novel serotonin 2C receptor antagonist, was recently approved as an adjunct to lifestyle modification for long-term weight loss and maintenance. Clinical studies in patients without diabetes demonstrated 5.8% mean weight loss from...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.798643
更新日期:2013-08-01 00:00:00
abstract:INTRODUCTION:Extensive within-population variability is the essence of neonatal pharmacology. Despite this, infants remain one of the last therapeutic orphans. Together with additional legal initiatives, tailoring of already available tools (modeling, covariates, pharmacovigilance) may significantly improve pharmacothe...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.931937
更新日期:2014-08-01 00:00:00
abstract:INTRODUCTION:The elucidation of the toxicological mechanisms of herbal medicines is becoming more and more important with the increasing application of herbal medicines, for treatment of various diseases and the promotion of health. Furthermore, it is widely recognized that as herbal components undergo bioactivation, t...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.586335
更新日期:2011-08-01 00:00:00
abstract:INTRODUCTION:Mortality from invasive fungal disease involving the central nervous system (CNS) is excessive. Achieving therapeutic drug concentrations at the site of infection within the CNS is always difficult and its evaluation is complex due to anatomical barriers and variable pathophysiological lesions. Areas cover...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2018.1492551
更新日期:2018-08-01 00:00:00
abstract:INTRODUCTION:Sumatriptan was developed more than 20 years ago as a 5-HT1B/1D receptor agonist, the first drug in a new class of specific anti-migraine drugs, the triptans. A large amount of information and experience has been gained from the clinical trials undertaken as well the various formulations of sumatriptan use...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.744394
更新日期:2013-01-01 00:00:00
abstract:INTRODUCTION:The absorption, distribution, metabolism, excretion and toxicity (ADME-tox) processes of drugs are of importance and require preclinical investigation intestine in addition to the liver. Various models have been developed for prediction of ADME-tox in the intestine. In this review, precision-cut intestinal...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2016.1125882
更新日期:2016-01-01 00:00:00
abstract:INTRODUCTION:The key feature of the newborn is its fast age-dependent maturation, resulting in extensive variability in pharmacokinetics and -dynamics, further aggravated by newly emerging covariates like treatment modalities, environmental issues or pharmacogenetics. This makes clinical research in neonates relevant a...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1046433
更新日期:2015-07-01 00:00:00
abstract:INTRODUCTION:The second-line treatment of endometriosis-related pain symptoms includes injectable depot formulations of gonadotropin-releasing hormone analogs (GnRH-as). These drugs improve the symptomatology by inducing a hypoestrogenic status and a consequent regression of endometriotic implants. However, GnRH-a may ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2020.1789591
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:The importance of transporters in drug disposition and response has led to increasing interest in genetic variations and expression differences of their genes. OBJECTIVE:This review summarizes: i) genetic variations in transporters and associated drug response; and ii) a pharmacogenomic approach to correlat...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.3.237
更新日期:2008-03-01 00:00:00