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您的检索式：作者名="Taoqian Zhao"
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| 1 | Development of the triazole-fused pyrimidine derivatives as highly potent and reversible inhibitors of histone lysine specific demethylase1(LSD1/KDM1A)显示文摘Histone lysine specific demethylase 1(LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound 8 a(IC50=3.93 μmol/L) and further medicinal chemistry efforts, leading to the generation of compound 15 u(IC50=49 nmol/L, and Ki= 16 nmol/L), which inhibited LSD1 reversibly and competitively with H3 K4 me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency ofcompound 15 u. Compound 15 u also showed strong antiproliferative activity against four leukemia cell lines(OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC50 values of 1.79, 1.30, 0.45, 1.22 and 1.40 μmol/L, respectively. In THP-1 cell line, 15 u significantly inhibited colony formation and caused remarkable morphological changes. Compound 15 u induced expression of CD86 and CD11 b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation.The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazolefused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1 A inhibitors. | Zhonghua Li Lina Ding Zhongrui Li Zhizheng Wang Fengzhi Suo Dandan Shen Taoqian Zhao Xudong Sun Junwei Wang Ying Liu Liying Ma Bing Zhao Pengfei Geng Bin Yu Yichao Zheng Hongmin Liu | 2019 | Acta Pharmaceutica Sinica B2019，9，4： | 6 |
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