• Our CiPA Instruments

    Patchliner & SyncroPatch 384PE (CiPA ion channel working group); CardioExcyte 96 (CiPA myocyte working group)

  • CiPA hERG Protocol

    This protocol was used for hERG studies on the Patchliner and SyncroPatch 384PE.

  • HTS CiPA hERG Assay

    Effects of Cisapride using the CiPA hERG protocol on the SyncroPatch 384PE

  • Myocyte & Ion Channel Effects

    Arrhythmic Field potentials in iPSC-derived Cardiomyocytes (CardioExcyte 96) and hERG current inhibition (SyncroPatch 384PE)

  • Gigaseal HTS patch clamp

    CiPA-specified cardiac ion channels recorded at high throughput

  • Gigaseal HTS patch clamp

    High throughput recordings of cardiac ion channels at physiological temperature

  • CardioExcyte 96 screening tool

    CardioExcyte 96 with integrated liquid handling for cardiac safety screening

2017 - An impedance-based approach using human iPSC-derived cardiomyocytes significantly improves in vitro prediction of in vivo cardiotox liabilities

Icon CE  CardioExcyte 96 publication in Toxicology and Applied Pharmacology (2017)

Authors: 
Koci B., Luerman G., Duenbostell A., Kettenhofen R., Bohlen H., Coyle L., Knight B., Ku W., Volberg W., Woska Jr. J.R., Brown M.P.

 

Journal: 
Toxicology and Applied Pharmacology (2017) 329:121-127


Highlights: 

  • Assessment of the impedance platform to predict both chronic and acute in vivo cardiotoxicity.
  • Cardiac functional and structural cardiotoxicity was evaluated.
  • The impedance assay predicted > 80% of known in vivo cardiotoxicity.
  • Data supports utilization of this assay for early drug discovery cardiac safety profiling

Abstract:

Current in vitro approaches to cardiac safety testing typically focus on mechanistic ion channel testing to predict in vivo proarrhythmic potential. Outside of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, structural and functional cardiotoxicity related to chronic dosing effects are of great concern as these effects can impact compound attrition. Development and implementation of an in vitro cardiotoxicity screening platform that effectively identifies these liabilities early in the discovery process should reduce costly attrition and decrease preclinical development time. Impedence platforms have the potential to accurately identify structural and functional cardiotoxicity and have sufficient throughput to be included in a multi-parametric optimization approach. Human induced pluripotent stem cell cardiomyocytes (hIPSC-CMs) have demonstrated utility in cardiac safety and toxicity screening. The work described here leverages these advantages to assess the predictive value of data generated by two impedance platforms. The response of hIPSC-CMs to compounds with known or predicted cardiac functional or structural toxicity was determined. The compounds elicited cardiac activities and/or effects on “macro” impedance often associated with overt structural or cellular toxicity, detachment, or hypertrophy. These assays correctly predicted in vivo cardiotox findings for 81% of the compounds tested and did not identify false positives. In addition, internal or literature Cmax values from in vivo studies correlated within 4 fold of the in vitro observations. The work presented here demonstrates the predictive power of impedance platforms with hIPSC-CMs and provides a means toward accelerating lead candidate selection by assessing preclinical cardiac safety earlier in the drug discovery process.


Download here

Back to Overview

Cookies make it easier for us to provide you with our services. With the usage of our services you permit us to use cookies.
More information Ok