BI 639667, a compound belonging to the azaindazole class, functions as a potent inhibitor of CCR1 activity, a property quantitatively demonstrated by its half-maximal inhibitory concentration (IC50) of 1.8 nM in standardized calcium flux assays.

CCR1:1.8 nM

Methods: Venlafaxine and paroxetine, which are marketed for the treatment of depression, were selected as positive drugs for affinity comparison. Molecular docking studies were performed using IL1R1 (PDB ID: 4gaf) and CCR1 antagonist 8 (BI 639667) to evaluate their binding energy with IL1R1, and further visualization was achieved through docking simulation with ILIRI.
Results: BI 639667 exhibited the lowest binding energy; the root mean square deviation (RMSD) Results showed that the fluctuation of the system was within 0.1 nm, indicating that the system had strong stability. The solvent accessible surface area (SASA) showed that the binding of BI 639667 had little effect on the structure of IL1R1. Further calculations of the hydrogen bond contacts between BI 639667 and IL1R1 were consistent with the docking Results, and the complex was able to form stable hydrogen bonds. [2]