Design,Synthesis And Biological Activity For Small Molecular Inhibitor Of SENP1

In this paper,we used the computational chemistry,medicinal chemistry and chemical biology,virtual screening,molecular docking,chemical systhesis and biological activity to design and systhesis novel small molecule inhibitor of SENP1 and we also studied the anti-prostate activity of them in vitro.This paper was mainly focused on the design,synthesis and biological activity of small molecule inhibitors of SENP1.As an important posttranslational protein modification,SUMO modification has many biological functions such as involved in transcription factor process regulation,development,growth,and differentiation of the cells due to the diversity of the modified substrate proteins.At the same time,SUMO was a dynamic and reversible process and de-SUMOylation was completed by SUMO-specific protease(SENPs).SENPs were one of the specific of cysteine protease and the SENP1 was very important in this family.SENP1 was able to remove the SUMO modification of protein so as to mediate the physiological function of the cell,and we also found that the abnormal expression of the SENP1 was related to many diseases especially in prostate cancer.Hence,we wanted to treat the prostate cancer by inhibiting the SENP1 protein so that this could become a new durg target for cancer treatment.By docking,virtual screening and testing the compound in vitro,we found the novel SENP1 leading compound.Then we systhesize the new compounds according to the structure of the leading compound and found a series of novel SENP1 small mocecule inhibitors.These could provide a good reference value for design of the SENP1 small molecule.