hERG Channel Electrophysiology Services

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

• Addexbio 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.

• Addexbio 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 AddexBio 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.

Related References to hERG Service:

1. Berglund, S., Egner, B. J., Graden, H., Graden, J., Morgan, D. G., Inghardt, T., and Giordanetto, F. Optimization of piperidin-4-yl-urea-containing melanin-concentrating hormone receptor 1 (MCH-R1) antagonists: Reducing hERG-associated liabilities. Bioorg Med Chem Lett, 19: 4274-4279, 2009.
2. Bowlby, M. R., Peri, R., Zhang, H., and Dunlop, J. hERG (KCNH2 or Kv11.1) K+ channels: screening for cardiac arrhythmia risk. Curr Drug Metab, 9: 965-970, 2008.
3. Gu, D. F., Li, X. L., Qi, Z. P., Shi, S. S., Hu, M. Q., Liu, D. M., She, C. B., Lv, Y. J., Li, B. X., and Yang, B. F. Blockade of HERG K+ channel by isoquinoline alkaloid neferine in the stable transfected HEK293 cells. Naunyn Schmiedebergs Arch Pharmacol, 380: 143-151, 2009.
4. Irie, O., Kosaka, T., Kishida, M., Sakaki, J., Masuya, K., Konishi, K., Yokokawa, F., Ehara, T., Iwasaki, A., Iwaki, Y., Hitomi, Y., Toyao, A., Gunji, H., Teno, N., Iwasaki, G., Hirao, H., Kanazawa, T., Tanabe, K., Hiestand, P. C., Malcangio, M., Fox, A. J., Bevan, S. J., Yaqoob, M., Culshaw, A. J., Hart, T. W., and Hallett, A. Overcoming hERG issues for brain-penetrating cathepsin S inhibitors: 2-cyanopyrimidines. Part 2. Bioorg Med Chem Lett, 18: 5280-5284, 2008.
5. Nakamura, Y., Takahara, A., and Sugiyama, A. Famotidine neither affects action potential parameters nor inhibits human ether-a-go-go-related gene (hERG) K+ current. J Toxicol Sci, 34: 563-567, 2009.
6. Raschi, E., Ceccarini, L., De Ponti, F., and Recanatini, M. hERG-related drug toxicity and models for predicting hERG liability and QT prolongation. Expert Opin Drug Metab Toxicol, 5: 1005-1021, 2009.
7. Wisniowska, B. and Polak, S. hERG in vitro interchange factors--development and verification. Toxicol Mech Methods, 19: 278-284, 2009.