News Releases & Research Results Elucidation of the protein-drug complex structure of the hERG channel responsible for adverse effects - Usefulness of cryo-electron microscopy in avoiding serious adverse effects -

News Releases & Research Results

Outline

The results of the collaborative research project conducted by Chiba University, Institute of Material Structure Science, High Energy Accelerator Research Organization (KEK), and five companies (Axcelead Drug Discovery Partners, Inc., Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd., Daiichi Sankyo RD Novare Co., Ltd., and Takeda Pharmaceutical Company Limited).

The key results of this research project are as follows:

  • The complex structure of the “hERG (human ether-à-go-go related gene) channel” responsible for drug adverse effects and a drug (astemizole) that inhibits the hERG functions was elucidated at a resolution of 3.5 angstroms (Å, 1Å equals to 10-10 meters) by single-particle cryo-electron microscopy.
  • The results of this research project revealed the protein-drug complex structure responsible for serious adverse effects. Single-particle cryo-electron microscopy for drug development should facilitate the prediction of adverse effects and serve as a basic technology for their prevention.

This project was conducted with the support of the Platform Project for Supporting Drug Discovery and Life Science Research (BINDS) by AMED.

The results were published online in the American scientific journal “Structure” on January 15.

Article

Asai T., et al. Cryo-EM structure of K+-bound hERG channel complexed with the blocker astemizole Structure
DOI: 10.1016/j.str.2020.12.007

2021.1.15

Last updated 2021.1.15