InSilicoCARDIO - Model CiPA In Silico - Solution for Pharma
A new model that combines dynamic drug-hERG interactions and multichannel pharmacology to improve prediction of drugs’ torsadogenic risk
Broadly Validated
Developed by the Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Science at FDA
Display and Export
Results can be easily visualized and can be downloaded in JSON or CSV formats
Easy to Use
Well-designed wizard (user interface) that step by step guides the user through the setup and running of three different simulation workflows
CiPA In Silico can be used to set up three different simulation workflows: hERG fitting, Hill fitting, and AP simulation.
hERG fitting performs uncertainty characterization for drug binding kinetics of the human Ether-à-go-go-Related Gene (hERG) channel gating model. It requires the upload of a CSV file containing laboratory data on time of recording, fractional current recorded, drug concentration, cell, and sweep number.
Hill fitting performs uncertainty characterization of dose-response curves for up to six ionic currents (ICaL, INaL, INa, Ito, IKs, and IK1). It requires the upload of a CSV file containing pharmacology data on drug concentration, ion channel type and percentage of ion channel block.
AP simulation combines the results of the modules hERG fitting and Hill fitting to simulate for a compound at a given concentration its effects on the Action Potential (AP) of a population of ventricular cardiomyocyte cells and to estimate from them the population value of the safety marker qNet and its uncertainty interval. The module requires the upload of CSV files for hERG and Hill fitting as described before. In addition, it requires the expected maximal therapeutic concentration (Cmax) of the compound of interest and a few Cmax multipliers in the range 1 – 30.