http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Valente, Sergio,Liu, Yiwei,Schnekenburger, Michael,Zwergel, Clemens,Cosconati, Sandro,Gros, Christina,Tardugno, Maria,Labella, Donatella,Florean, Cristina,Minden, Steven,Hashimoto, Hideharu,Chang, Yan American Chemical Society 2014 Journal of medicinal chemistry Vol.57 No.3
<P/><P>DNA methyltransferases (DNMTs) are important enzymes involved in epigenetic control of gene expression and represent valuable targets in cancer chemotherapy. A number of nucleoside DNMT inhibitors (DNMTi) have been studied in cancer, including in cancer stem cells, and two of them (azacytidine and decitabine) have been approved for treatment of myelodysplastic syndromes. However, only a few non-nucleoside DNMTi have been identified so far, and even fewer have been validated in cancer. Through a process of hit-to-lead optimization, we report here the discovery of compound <B>5</B> as a potent non-nucleoside DNMTi that is also selective toward other AdoMet-dependent protein methyltransferases. Compound <B>5</B> was potent at single-digit micromolar concentrations against a panel of cancer cells and was less toxic in peripheral blood mononuclear cells than two other compounds tested. In mouse medulloblastoma stem cells, <B>5</B> inhibited cell growth, whereas related compound <B>2</B> showed high cell differentiation. To the best of our knowledge, <B>2</B> and <B>5</B> are the first non-nucleoside DNMTi tested in a cancer stem cell line.</P>