Increased Molecular Flexibility Widens the Gap between K _i and K _d values in Screening for Retinoid X Receptor Modulators.

ABSTRACT: Screening for small-molecule modulators targeting a particular receptor is frequently based on measurement of K _d, i.e., the binding constant between the receptor and the compound of interest. However, K _d values also reflect binding at receptor protein sites other than the modulatory site. We designed derivatives of retinoid X receptor (RXR) antagonist CBTF-EE (1) with modifications that altered their conformational flexibility. Compounds 6a,b and 7a,b showed quite similar K _d values, but 7a,b exhibited 10-fold higher K _i values than those of 6a,b. Further, 6a,b showed potent RXR-antagonistic activity, while 7a,b were inactive.

SUBMITTER: Watanabe M 

PROVIDER: S-EPMC8842113 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature