Quantitative receptor model for responses that are left- or right-shifted versus occupancy (are more or less concentration sensitive): the SABRE approach.

ABSTRACT: Simple one-to three-parameter models routinely used to fit typical dose-response curves and calculate EC₅₀ values using the Hill or Clark equation cannot provide the full picture connecting measured response to receptor occupancy, which can be quite complex due to the interplay between partial agonism and (pathway-dependent) signal amplification. The recently introduced SABRE quantitative receptor model is the first one that explicitly includes a parameter for signal amplification (γ) in addition to those for binding affinity (K _d), receptor-activation efficacy (ε), constitutive activity (ε _R0), and steepness of response (Hill slope, n). It can provide a unified framework to fit complex cases, where fractional response and

SUBMITTER: Buchwald P 

PROVIDER: S-EPMC10755021 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature