De novo design of PD-1/PD-L1 small molecule inhibitors based on fragment growth technology
Objective To develop a variety of small molecule PD-L1 inhibitors based on fragment growth.Methods Based on the known structure of benzoyl aniline active fragment,the fragment growth was obtained via the FDA fragment library,and further screened with molecular docking and molecular dynamics.Finally,active compounds were obtained through the in vitro experiment.Results A series of molecular libraries containing benzoyl aniline fragment were obtained,including 8 highly rated molecules.Molecular dynamics simulations showed that molecule 776191 had the highest binding energy,and in vitro inhibition experiment showed that molecule 776191 had certain inhibition against PD-1/PD-L1 binding.Conclusion Molecule 776191 is a PD-1/PD-L1 inhibitor with a novel structure,which enriches the diversity of PD-1/PD-L1 inhibitors and provides new design ideas.
drug designPD-1/PD-L1small molecule inhibitormolecular dynamics simulationfragment growth technology
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