A5046484964- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Analytical Methods in Pharmaceuticals
- Computational Drug Discovery Methods
- Electrochemical Analysis and Applications
- ECG Monitoring and Analysis
- Receptor Mechanisms and Signaling
- Semiconductor materials and devices
- Phytochemicals and Medicinal Plants
Universitat Politècnica de València
2018-2020
Preclinical assessment of drug-induced proarrhythmicity is typically evaluated by the potency drug to block potassium human ether-à-go-go-related gene (hERG) channels, which currently quantified IC50. However, channel depends on experimental conditions. Our aim improve evaluation blocking drugs designing stimulation protocols measure IC50 that will help decide whether representative enough. We used state-of-the-art mathematical models cardiac electrophysiological activity design three...
Drug-induced proarrhythmicity is a major concern for regulators and pharmaceutical companies. For novel drug candidates, the standard assessment involves evaluation of potassium hERG channels block in vivo prolongation QT interval. However, this method known to be too restrictive stop development potentially valuable therapeutic drugs. The aim work create an silico tool early detection drug-induced proarrhythmic risk. system based on simulations how different compounds affect action...
Drug-induced torsade de pointes (TdP) is a life-threatening ventricular arrhythmia responsible for the withdrawal of many drugs from market. Although currently used TdP risk-assessment methods are effective, they expensive and prone to produce false positives. In recent years, in silico cardiac simulations have proven be valuable tool prediction drug effects. The objective this work evaluate different biomarkers drug-induced proarrhythmic risk develop an classifier. Cellular were performed...
The prolongation of the QT interval represents main feature long syndrome (LQTS), a life-threatening genetic disease. heterozygous SCN5A V411M mutation human sodium channel leads to LQTS type 3 with severe proarrhythmic effects due an increase in late component current (INaL). two blockers flecainide and ranolazine are equally recommended by 2015 ESC guidelines treat patients persistently prolonged intervals. However, awareness pro-arrhythmic arose upon study E1784K mutation. Regarding...
Companies and regulators evaluate compounds' cardiac safety commonly through in-vitro assays involving cells. Rabbit cardiacPurkinje Cells (RPCs) are very sensitive to drug effects such as Action Potential Duration (APD) alteration by ion channel block.Our objective is create a novel RPC model calibrated with the latest experimental data.We developed new using Pan-Rudy's Canine Purkinje cell framework.We adapted important parameters, namely, size, fluxes conductances.We also included sodium...
Abstract Introduction It is well recognized that early identification of drug-induced proarrhythmic safety risks crucial to drug development for ethical, animal sparing and costs reduction considerations. The availability, however, easily accessible, user-friendly tools real time assessments the potential chemical compounds has been lacking. novel Tx index, implemented in presented web-based tool, was applied a dataset 84 compounds. Materials methods tool based on 206,766 cellular...