Abstract:
:There is currently a strong interest in using high-throughput in-vitro ion-channel screening data to make predictions regarding the cardiac toxicity potential of a new compound in both animal and human studies. A recent FDA think tank encourages the use of biophysical mathematical models of cardiac myocytes for this prediction task. However, it remains unclear whether this approach is the most appropriate. Here we examine five literature data-sets that have been used to support the use of four different biophysical models and one statistical model for predicting cardiac toxicity in numerous species using various endpoints. We propose a simple model that represents the balance between repolarisation and depolarisation forces and compare the predictive power of the model against the original results (leave-one-out cross-validation). Our model showed equivalent performance when compared to the four biophysical models and one statistical model. We therefore conclude that this approach should be further investigated in the context of early cardiac safety screening when in-vitro potency data is generated.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Mistry HB,Davies MR,Di Veroli GYdoi
10.3389/fphar.2015.00059subject
Has Abstractpub_date
2015-03-24 00:00:00pages
59issn
1663-9812journal_volume
6pub_type
杂志文章abstract::Liver fibrosis, a chronic damage process related to further progression of hepatic cirrhosis, has yet no truly effective treatment. Isochlorogenic acid A (ICQA), isolated from a traditional Chinese herbal medicine named Laggera alata (DC.) Sch.Bip. ex Oliv. (Asteraceae), is proved to exhibit anti-inflammatory, hepatop...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00582
更新日期:2020-05-01 00:00:00
abstract::The immune system is complex and pervasive as it functions to prevent or limit infections in the human body. In a healthy organism, the immune system and the redox balance of immune cells maintain homeostasis within the body. The failure to maintain the balance may lead to impaired immune response and either over acti...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2017.00022
更新日期:2017-01-30 00:00:00
abstract::The pentose phosphate pathway (PPP), which branches from glycolysis, is correlated with cancer cell proliferation, survival and senescence. In this study, differences in the metabolic profile of the PPP and the redox status of human lung carcinoma A549 cells and cisplatin-induced multidrug-resistant A549/DDP cells wer...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00043
更新日期:2018-01-31 00:00:00
abstract::This article highlights several refractory oral diseases, such as stomatitis, burning mouth syndrome (BMS), glossalgia, atypical facial pain (AFP), oral cancer, dry mouth, and Sjögren's syndrome (SJS), in which use of Japanese herbal medicines, Kampo medicines (KM), on the basis of Kampo theory could exert the maximum...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2015.00176
更新日期:2015-08-28 00:00:00
abstract::Background: Shexiang Baoxin Pill (SBP) is a well-known composite formula of traditional Chinese medicine (TCM), which is commonly used today in treating cardiovascular diseases. SBP consists of seven materials thereof, including Moschus, extract of Ginseng Radix et Rhizoma, Bovis Calculus Artifactus, Cinnamomi Cortex,...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01130
更新日期:2019-10-09 00:00:00
abstract::Wenxin Keli (WXKL) is a widely used Chinese botanical drug for the treatment of arrhythmia, which is consisted of four herbs and amber. In the present study, we analyzed the chemical composition of WXKL using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) to tentatively identify 71 comp...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01288
更新日期:2018-11-13 00:00:00
abstract::Intestinal barrier dysfunction is an important clinical problem in various acute and chronic pathological conditions. Ferulic acid (FA) can attenuate the intestinal epithelial barrier dysfunction, however, the underlying mechanism remains unclear. The present study aimed to uncover the protective effect of FA on intes...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00376
更新日期:2020-04-03 00:00:00
abstract::[This corrects the article DOI: 10.3389/fphar.2020.00512.]. ...
journal_title:Frontiers in pharmacology
pub_type: 已发布勘误
doi:10.3389/fphar.2020.00772
更新日期:2020-05-29 00:00:00
abstract::Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly under...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2015.00143
更新日期:2015-07-21 00:00:00
abstract::The development of compounds able to modify biological functions largely took advantage of parallel synthesis to generate a broad chemical variance of compounds to be tested for the desired effect(s). The budding yeast Saccharomyces cerevisiae is a model for pharmacological studies since a long time as it represents a...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00170
更新日期:2017-03-30 00:00:00
abstract::Thienorphine (TNP) is a novel partial opioid agonist that has completed phase II clinical evaluation as a promising drug candidate for the treatment of opioid dependence. Previous studies have shown that TNP and its glucuronide conjugate (TNP-G) undergo significant bile excretion. The purpose of this study was to inve...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00242
更新日期:2016-08-09 00:00:00
abstract::The dermis of human skin contains large numbers of fibroblasts that are responsible for the production of the extracellular matrix (ECM) that supporting skin integrity, elasticity and wound healing. Previously, an in vivo study demonstrated that dermal fibroblasts siting in the lower dermis are capable to convert into...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00155
更新日期:2018-03-06 00:00:00
abstract::ORY-1001, an inhibitor of covalent lysine (K)-specific demethylase 1A (KDM1A), has been used as a therapy for the treatment of acute leukemia. However, the underlying mechanisms of anticancer are still not fully elucidated. Here, we report that KDM1A is highly expressed in lung cancers, where it appears to drive aggre...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01411
更新日期:2018-12-04 00:00:00
abstract:Background and Aim:Platycodon grandiflorum (PG) has been widely used for treating chronic bronchitis (CB). However, the material basis and underlying mechanism of action of PG against CB have not yet been elucidated. Methods:To analyze the ingredients in PG, ultraperformance liquid chromatography-quadrupole-time-of-fl...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.564131
更新日期:2020-09-08 00:00:00
abstract::The melanocortin-4 receptor (MC4R) is a potential drug target for treatment of obesity, anxiety, depression, and sexual dysfunction. Crystal structures for MC4R are not yet available, which has hindered successful structure-based drug design. Using microsecond-scale molecular-dynamics simulations, we have investigated...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00560
更新日期:2018-06-01 00:00:00
abstract:Background:Salvianolate, a compound mainly composed of salvia magnesium acetate, is extracted from the Chinese herb Salvia miltiorrhiza. Because of its biological activity, easy quality control and certain efficacy, salvianolate is widely used in treating ischemic cardiocerebral vascular disease, liver damage, renal in...
journal_title:Frontiers in pharmacology
pub_type:
doi:10.3389/fphar.2020.00851
更新日期:2020-06-12 00:00:00
abstract:PURPOSE:The importance of a framework for a systematic structured assessment of the benefits and risks has been established, but in addition, it is necessary that the benefit-risk decisions and the processes to derive those decisions are documented and communicated to various stakeholders for accountability. Hence ther...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2015.00099
更新日期:2015-06-11 00:00:00
abstract::Purpose: The present study compared the risk of ischemic stroke in atrial fibrillation (AF) patients receiving digoxin and amiodarone. Methods: A retrospective cohort study was conducted using the longitudinal population-based database of Taiwan's National Health Insurance program. Patients with AF who received amioda...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00448
更新日期:2018-05-07 00:00:00
abstract::Coronavirus disease 2019 (COVID-19), an acute onset pneumonia caused by a novel Betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in the Wuhan City of China in December 2019 and evolved into a global pandemic. To date, there are no proven drugs or vaccines against this virus. Hence...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.585888
更新日期:2020-09-17 00:00:00
abstract::The aim of this experimental study was to assess whether 5 weeks of preoperative supplementation with vitamin D affects the intensity of pain and the level of inflammatory markers in patients undergoing posterior lumbar interbody fusion (PLIF) followed by rehabilitation. 42 patients were divided, by double-blind rando...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00527
更新日期:2019-05-22 00:00:00
abstract::Cisplatin, as the first-line anti-tumor agent, is widely used for treatment of a variety of malignancies including non-small cell lung cancer (NSCLC). However, the acquired resistance has been a major obstacle for the clinical application. Scutellarin is a active flavone extracted from Erigeron breviscapus Hand-Mazz t...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00092
更新日期:2018-02-13 00:00:00
abstract::Aging leads to changes in nearly all pharmacokinetic phases. Koumine (KM), an alkaloid derived from Gelsemium elegans Benth., is effective against age-associated chronic diseases, but its dose proportionality following oral administration in aged individuals remains unknown. Herein, we established and validated a simp...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.01113
更新日期:2020-07-21 00:00:00
abstract::Dizocilpine (MK-801) is a non-competitive NMDA antagonist that induces schizophreniclike effects. It is therefore widely used in experimental models of schizophrenia including prepulse inhibition (PPI) impairments in rodents. Nevertheless, MK-801 has never been tested in monkeys on a PPI paradigm. In order to evaluate...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2015.00204
更新日期:2015-09-22 00:00:00
abstract::The interaction between T cell and dendritic cells (DCs) that leads to T cell activation affects the progression of the immune response including autoimmune diseases. Antigen presentation on immune cell surface, formation of an immunological synapse (IS), and specific identification of complex by T cells including two...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2018.00642
更新日期:2018-06-26 00:00:00
abstract::P-Glycoprotein (P-gp, Abcb1) plays a crucial role in drug disposition and functions by hydrolyzing ATP. However, little is known about the regulatory elements governing the transcription of the porcine Abcb1 gene. In this study, the transcription start site of the pig Abcb1 gene was identified by 5'-RACE. A 1.9-kb fra...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00373
更新日期:2018-05-04 00:00:00
abstract::Impulse generation in supraventricular tissue is inhibited by adenosine and acetylcholine via the activation of A1 and M2 receptors coupled to inwardly rectifying GIRK/KIR3.1/3.4 channels, respectively. Unlike M2 receptors, bradycardia produced by A1 receptors activation predominates over negative inotropy. Such diffe...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00045
更新日期:2016-03-07 00:00:00
abstract::Background: The research into bioactive natural products of medicinal plants has a long tradition, but ethnopharmacology as a well-defined field of research has a relatively short history, only dating back 50 years. Aims: With the fast development of this field and its global importance especially in the fast developi...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00215
更新日期:2018-03-15 00:00:00
abstract::Gout is a type of arthritis that causes painful inflammation in one or more joints. In gout, elevation of uric acid in the blood triggers the formation of crystals, causing joint pain. Malaysia is a mega-biodiversity country that is rich in medicinal plants species. Therefore, its flora might offer promising therapies...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2018.00261
更新日期:2018-03-23 00:00:00
abstract::Lung cancer is one of main causes of cancer mortality and 83% of lung cancer cases are classified as non-small cell lung cancer (NSCLC). Patients with NSCLC usually have a poor prognosis and one of the leading causes is drug resistance. With the progress of drug therapy, the emergence and development of drug resistanc...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.01457
更新日期:2019-12-18 00:00:00
abstract::Vascular calcification is a major complication of cardiovascular disease and chronic renal failure. Autophagy help to maintain a stable internal and external environment that is important for modulating arteriosclerosis, but its pathogenic mechanism is far from clear. Here, we aimed to identify the bioactive compounds...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01427
更新日期:2019-12-19 00:00:00