NGHIÊN CỨU SÀNG LỌC IN SILICO CÁC PHÂN TỬ NHỎ CÓ KHẢ NĂNG ỨC CHẾ PD-L1

Summary
Immunotherapy is a revolutionary in cancer treatment, especially in advanced stage, combined with radiotherapy and/or chemotherapy. PD-1/PD-L1 is an important checkpoint, has been applied in treatment and is being continued in clinical trial in the form of monoclonal antibodies in the recent years. However, the disadvantages of therapeutic antibodies may limit their applications due to immune-related adverse effects (irAEs), poor bioavailability and cost. Thus, inhibitors of the PD-1/PD-L1 by small molecules may be a promising alternative for cancer immunotherapy. We performed a five-point pharmacophore modeling to screen database libraries for substance targeting PD-L1. Then, an online ADME assessment on SwissADME helps to review physicochemical descriptors as well as to predict ADME parameters, pharmacokinetic properties, drug-likeness and medicinal chemistry friendliness of small molecules. Molecular docking study revealed that these 2668 substances have high binding affinity for the central cavity (docking scores ranged from -45.38 kJ/mol to -13.12 kJ/mol) All of them bind with residues Tyr56, Asp122 are the two most important roles in interaction between protein and ligand. The study recommended 7 potential substances conducting molecular dynamics simulation, free energy binding and invitro testing.

Keywords: PD-L1, immune checkpoint inhibitor, small-molecule inhibitors, cancer immunotherapy, virtual screening.

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