Approximately one third of compounds in pre-clinical development exhibit some levels of cardiac risks. Unfortunately, many of these compounds are not identified until they are in clinical trials after millions of dollars and years of effort have been invested. As a result, the vast majority of investigational products that enter clinical trials fail. Therefore, for the sake of saving time and money, it is critical to assess the preclinical cardiac safety of these investigational products before they enter clinical trials.

The hERG channel plays a significant role in cardiac repolarization and acute hERG block alone will prolong QT and induce Torsades de Pointes. Compounds routinely affect The hERG channel influencing the effect of hERG block. BioMaxLab provides a fast, comprehensive preclinical cardiac safety assessment for full resolution of potential cardiac risk prior to IND submission. Multiple assays are employed to assess a compound's effect on preclinical cardiac safety at molecular, cellular, tissue and system levels. We enable you to achieve nearly 100% predictivity of cardiac risk with our preclinical cardiac safety assessment. BioMaxLab provides the most complete preclinical cardiac safety package presently available.

 

Molecular structure of hERG

hERG Channel Electrophysiology Overview

Drug-induced delayed cardiac repolarization has associated with block of hERG (a functionally prominent ventricular repolarizing potassium current) and is linked to cardiac proarrhythmia (Torsades-de-Pointes). However, hERG current block is not always associated with delayed repolarization, and preclinical cardiac safety studies evaluating only hERG current provide a focused but narrow perspective. Additional cardiac ion channels represent numerous potential off-target effects that may modulate the effects of hERG current block, affect impulse initiation (chronotropic effects), conduction (dromotropic effects), or contractility (inotropic effects). Routine hERG screening in early discovery efforts should be supplemented with additional studies to avoid unduly discarding hERG blocking drugs not affecting delayed repolarization and to ensure overall cardiac safety.

Assessing hERG Channel Inhibition

  • BioMaxLab uses manual patch clamp (a gold standard) to assess hERG channel inhibition on HEK293 cells or CHO cells stably transfected with the hERG ion channel.
  • BioMaxLab uses manual patch clamp (a gold standard) to assess hERG channel inhibition on HEK293 cells or CHO cells stably transfected with the hERG ion channel.
  • Protocols include exploratory non-GLP screening of single high concentration or IC50.
  • Validated with a number of agents known to affect the hERG current, including terfenadine, cisapride and E-4031.

The BioMaxLab Difference

  • A customer focused approach, delivering beyond your expectations.
  • Scientific excellence with over 20 years combined experience in in vitro pharmacology and a technical team with the same high standards as yours.
  • A quality service.
  • A flexible service; we support a cross-section of global clients, from small biotech to large pharmaceutical companies, and academia, providing both validated assays and tailored protocols.
If your drug has a positive effect on hERG channel, does it have a QT risk? The follow-up studies to the heart models in vitro can provide greater depth of understanding or additional knowledge regarding the potential of test substance for delayed ventricular repolarization and QT interval prolongation in humans. BioMaxLab offers a heart model in vitro QT service to characterize a drug's potential to affect ventricular repolarization and contractility. Early testing for multiple effects on key cardiac ion channels fully resolves discordances and prevents advancement of cardiotoxic drug candidates. Using isolated rat or rabbit hearts, BioMaxLab offers Langendorff perfused heart ECG and contractility assessment so that drugs can be tested on isolated animal hearts. We can identify effects of your compounds on the ECG (QT interval, QRS), heart contractility (LVDP, dP/dt) and coronary flow. Three hearts will be used per concentration. Final reports of the in vitro QT service include drug effects on the study parameters including a summary of the results, description of methods used, statement of quality standard, and any amendments or deviations included as an appendix
The in vivo QT Service is a component of BioMaxLabs preclinical cardiac safety assessment, a comprehensive cardiac safety assessment package for full resolution of potential cardiac risk prior to IND submission. Using rat, rabbit or dog, BioMaxLab can determine the effects of drugs on ECG in vivo, such as QT/QTc interval, QRS duration, RR interval, PR interval. Three animals will be used per concentration. Final reports of the in vivo QT service include drug effects on the study parameters including a summary of the results, description of methods used, statement of quality standard, and any amendments or deviations included as an appendix.
Cardiac hemodynamic assessment is another component of BioMaxLabs preclinical cardiac safety assessment. Using rat, rabbit or dog, BioMaxLab can determine the effects of drugs on cardiac hemodynamic parameters, such as heart rate, arterial blood pressure (including systolic, diastolic and mean arterial blood pressure), heart contractility (LVDP, dP/dt) and coronary flow. Three animals will be used per concentration. Final reports of the cardiac hemodynamic assessment include drug effects on the study parameters including a summary of the results, description of methods used, statement of quality standard, and any amendments or deviations included as an appendix.
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