Design of dual-target inhibitors of DPP-4 and SGLT-2 based on BiRNN model
Objective To design a dual-target inhibitor of DPP-4 and SGLT-2.Methods The BiRNN model was trained according to the existing DPP-4 and SGLT-2 active compounds to generate new dual-target molecules with potential activity,and the HipHop pharmacophore model was constructed using the reported active compounds,and the new molecules were pre-screened through the pharmacophore model,and then the small molecules were further screened by molecular docking,molecular dynamics simulation and combined free energy calculation,and the candidate compounds were finally obtained.Results A total of 7 494 new molecules were generated by the BiRNN model,and the compounds NM186,NM21,NM249,and NM107 were found to be relatively ideal dual-target inhibitors of DPP-4 and SGLT-2.Conclusion NM186,NM21,NM249 and NM107 may be dual-target inhibitors of DPP-4/SGLT-2 with novel structures,which enriches the diversity of DPP-4 and SGLT-2 dual-target inhibitors and provides new design ideas for their development.
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