"Network leaning" as a mechanism of insurmountable antagonism of the angiotensin II type 1 receptor by non-peptide antagonists.

@article{Takezako2004NetworkLA,
  title={"Network leaning" as a mechanism of insurmountable antagonism of the angiotensin II type 1 receptor by non-peptide antagonists.},
  author={Takanobu Takezako and Camelia Baleanu Gogonea and Yasser Saad and Keita Noda and Sadashiva S Karnik},
  journal={The Journal of biological chemistry},
  year={2004},
  volume={279 15},
  pages={15248-57}
}
A mechanistic understanding of the insurmountable antagonism of the angiotensin II type 1 (AT(1)) receptor could be fundamental in the quest for discovery and improvement of drugs. Candesartan and EXP3174 are competitive, reversible insurmountable antagonists of the AT(1) receptor. They contain di-acidic substitutions, whereas the surmountable antagonist, losartan, contains only one acidic group. We tested the hypothesis that these two classes of ligands interact with the AT(1) receptor through… CONTINUE READING