靶向IgE重链Fc段潜在拮抗药物筛选及拮抗效果分析OA

Objective To screen potential antagonistic drugs targeting immunoglobulin E(IgE)heavy chain Fc fragment,and evaluate their antagonistic effects.Methods Surface plasmon resonance(SPR)technology was used to perform high-throughput screening for drugs from the U.S.Food and Drug Administration approved drug library that bind to the recombinant human IgE Fc fragment(rhIgE-Fc,500,250,125,62.5,and 31.3 nmol/L).Molecular docking models of candidate drugs with the rhIgE protein were simulated,and the antagonistic effects of the candidate drugs against rhIgE were evaluated by indirect competitive enzyme-linked immunosorbent assay.Results Three drugs with strong binding affinity to the rhIgE-Fc fragment protein were identified:potassium andrographolide succinate,pinaverium bromide,and lipoic acid.The binding affinities of these three drugs were positively correlated with the concentration of the rhIgE-Fc fragment protein.Molecular docking results showed that all three candidate drugs effectively occupied the Fc fragment binding pocket of the rhIgE fragment protein,with molecular docking binding energies of-6.0,-5.3,and-4.4 kcal/mol,respectively.Compared with the currently clinically used IgE monoclonal antibody omalizumab(which exhibited a 31.57% antagonistic effect against rhIgE at 120 µg/mL),the mass concentrations required for potassium andrographolide succinate,pinaverium bromide,and lipoic acid to achieve an equivalent antagonistic effect were 86.04,60.86,and 167.23 ng/mL,respectively.Conclusion Potassium andrographolide succinate,pinaverium bromide,and lipoic acid can be used as potential IgE antagonist drugs for the treatment of acute allergic and chronic inflammatory allergic diseases.