Watanabe, Masaki published the artcileIncreased Molecular Flexibility Widens the Gap between Ki and Kd values in Screening for Retinoid X Receptor Modulators, Quality Control of 638-45-9, the publication is ACS Medicinal Chemistry Letters (2022), 13(2), 211-217, database is CAplus and MEDLINE.
Screening for small-mol. modulators targeting a particular receptor is frequently based on measurement of Kd, i.e., the binding constant between the receptor and the compound of interest. However, Kd values also reflect binding at receptor protein sites other than the modulatory site. We designed derivatives of retinoid X receptor (RXR) antagonist CBTF-EE (I) with modifications that altered their conformational flexibility. Compounds 6a,b and 7a,b showed quite similar Kd values, but 7a,b exhibited 10-fold higher Ki values than those of 6a,b. Further, 6a,b showed potent RXR-antagonistic activity, while 7a,b were inactive. These results suggest that increased conformational flexibility promotes binding at nontarget receptor sites. In this situation, conventional determination of Kd is less effective for screening purposes than the determination of Ki using a ligand that binds specifically to the site regulating transcriptional activity. Thus, the use of Ki values for orthosteric ligands may increase the hit rate in screening active regulatory mols.
ACS Medicinal Chemistry Letters published new progress about 638-45-9. 638-45-9 belongs to iodides-buliding-blocks, auxiliary class Iodide,Aliphatic hydrocarbon chain, name is 1-Iodohexane, and the molecular formula is C19H18O2, Quality Control of 638-45-9.
Referemce:
https://en.wikipedia.org/wiki/Iodide,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com