Probing the Histamine H₁ Receptor Binding Site to Explore Ligand Binding Kinetics.

ABSTRACT: Analysis of structure-kinetic relationships (SKR) can contribute to an improved understanding of receptor-ligand interactions. Here, fragment 1 (4-(2-benzylphenoxy)-1-methylpiperidine) was used in different fragment growing approaches to mimic the putative binding mode of the long residence time (RT) ligands olopatadine, acrivastine, and levocetirizine at the histamine H₁ receptor (H₁R). SKR analyses reveal that introduction of a carboxylic acid moiety can increase RT at H₁R up to 11-fold. Ligand efficiency (LE) decreases upon the introduction of the negatively charged group, whereas kinetic efficiency (KE) increases up to 8.5-fold. The olopatadine/acrivastine mimics give up to 15-fold differences in the RT, while the levocetirizine mimics afford sim

SUBMITTER: Kuhne S 

PROVIDER: S-EPMC11726634 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature