Predicting the Activation of the Androgen Receptor by Mixtures of Ligands Using Generalized Concentration Addition.

ABSTRACT: Concentration/dose addition is widely used for compounds that act by similar mechanisms. But it cannot make predictions for mixtures of full and partial agonists for effect levels above that of the least efficacious component. As partial agonists are common, we developed generalized concentration addition, which has been successfully applied to systems in which ligands compete for a single binding site. Here, we applied a pharmacodynamic model for a homodimer receptor system with 2 binding sites, the androgen receptor, that acts according to the classic homodimer activation model: Each cytoplasmic monomer protein binds ligand, undergoes a conformational change that relieves inhibition of dimerization, and binds to DNA response elements as a dimer. We generated individual dose-response data

SUBMITTER: Schlezinger JJ 

PROVIDER: S-EPMC7548291 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature