Molecular interaction between AMD-070 with human serum albumin: insights from network pharmacology, multispectral technology and computer simulation.

AMD-070 (also known as Xolremdi, Mavorixafor) is an immunotherapeutic agent approved in 2024 for the treatment of WHIM syndrome. This study integrates network pharmacology, multispectral spectroscopy, and computational simulations to investigate the interaction between AMD-070 and human serum albumin (HSA). Network pharmacological screening identified six candidate proteins that may bind AMD-070, among which HSA was predicted to have the strongest binding affinity. The binding mechanism demonstrates that the ligand spontaneously associates with HSA site I, driven mainly by hydrophobic forces and van der Waals interactions. Energy decomposition analysis identified ARG257 and LEU238 within site I as the key residues. Spectroscopic analyses using synchronous fluorescence (SF), Fourier-transform infrared (FT-IR), and circular dichroism (CD) suggest that AMD-070 binding causes modest conformational perturbations in HSA and alters the local microenvironment of aromatic amino acid residues. An increase in the radius of gyration (Rg) and an enrichment of favorable conformations within the free energy landscape (FEL) corroborate this conclusion. Additionally, AMD-070 inhibits HSA esterase-like activity in a dose-dependent manner, likely via interaction with ARG257. These findings provide a biophysical characterization of the HSA-AMD-070 interaction, offering a molecular basis for understanding its plasma protein binding behavior.