One Kind Of Small Molecule Inhibitor Of The Computer-aided Screening,Design,Synthesis And Biological Activity Study Of EZH2

In the past few years, epigenetic modifications such as DNA methylation, histone methylation and histone acetylation has shown anti-tumor therapeutic effects optimistic. Currently, a number of effective drugs, such as 5-Azacytidine and GSK126 have been used as one new anticancer drug in clinical practice. Histone methylation can be regarded as a highly reversible process, which with a variety of tumor formation and deterioration is closely linked. Since GSK126 as the first histone methylation inhibitor for anti-cancer drug into the market, so many researchers and their EZH2 inhibitors for further study. For EZH2 inhibition activity is considered to be a completely effective way to treat cancer. It is widely believed EZH2 mutation closely related functions in tumorigenesis.In this thesis, computer-aided drug design methods, the SPECS database effective screening small molecule compounds screened in theory, it has an effective suppression of EZH2, and then conduct a preliminary screening of the compound of structural modification, access for EZH2 inhibition good structural fragment active and effective structural synthesis of these fragments, and through certain synthetic splicing technology, to obtain the target compound, and tested for their activity, which found that these compounds are effective structure and benefits group, then these small molecule further modified the structure reasonable, and a series of synthetic analogues, and then measuring the biological activity of these analogs. In the synthesis of these compounds, FELI₄2 and FELI₂54 of EZH2 have significant inhibitory activity. Further experimental studies have shown that these compounds on tumor cell proliferation are inhibited. In a word, through the further optimization of the structure of these compounds can provide some useful guidance ideas for the development of EZH2 inhibitors, thereby providing new help for the treatment of cancer.