Discovery of novel chemical scaffolds as RhoA inhibitors using virtual screening, synthesis, and bioactivity evaluation
Discovery of novel chemical scaffolds as RhoA inhibitors using virtual screening, synthesis, and bioactivity evaluation
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使用虚拟筛选、合成和生物活性评估发现新型化学支架作为 RhoA 抑制剂
DOI：
10.1039/c6ra11398b
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发表时间：
2016-06
期刊：
影响因子：
3.9
通讯作者：
Xu Xiao-Li
中科院分区：
文献类型：
--
作者：
Zhang Chao;Wang Hui-Jie;Bao Qi-Chao;Bian Jin-Lei;Yang Ying-Rui;You Qi-Dong;Xu Xiao-Li
RhoA has been implicated in diverse cellular functions and is a potential cancer therapeutic target. Through virtual screening, we have identified a RhoA inhibitor, DDO-5701. DDO-5701 has an affinity to RhoA at the micromolar level in vitro. By structural modifications, considering the binding activity and synthesis ease of DDO-5701, 17 compounds were designed and synthesized accordingly. Among these compounds, 4 compounds (DDO-5713, DDO-5714, DDO-5715, DDO-5716) exhibited higher RhoA inhibition activities than DDO-5701, while DDO-5716 can effectively reverse the functions of breast cancer cells regulated by RhoA. Thus, the rationally designed small molecule inhibitor of RhoA (DDO-5716) is useful for studying the physiological and pathological roles of Rho GTPase. However, DDO-5701 is an approved drug – proglumide, which makes it and its derived compound DDO-5716 more likely to be well tolerated in humans and could quickly lead to further clinical development.
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影响因子：
--
作者：
Evelyn CR;Ferng T;Rojas RJ;Larsen MJ;Sondek J;Neubig RR
通讯作者：
Neubig RR
DOI：
10.1007/978-94-015-9460-8_17
发表时间：
2000
期刊：
--
影响因子：
--
作者：
Hai Li;Zhenbiao Yang
通讯作者：
Hai Li;Zhenbiao Yang
DOI：
--
发表时间：
1999-06
期刊：
Zhonghua wai ke za zhi [Chinese journal of surgery]
影响因子：
--
作者：
H. Wang;Q. Ni;Y. Zhang;Z. Yue;Q. Zhang;L. Hou
通讯作者：
H. Wang;Q. Ni;Y. Zhang;Z. Yue;Q. Zhang;L. Hou
影响因子：
64.8
作者：
Pertz, O;Hodgson, L;Hahn, KM
通讯作者：
Hahn, KM
影响因子：
4.8
作者：
Amano, M;Ito, M;Kaibuchi, K
通讯作者：
Kaibuchi, K