二芳基甲酮化合物抑制SHP2生物活性研究
Biological Evaluation of Diaryl Ketones against SHP2
DOI: 10.12677/HJMCe.2019.72004, PDF,    国家自然科学基金支持
作者: 范秋玥, 张传涛, 王文龙*：江南大学药学院，江苏 无锡
关键词: 二芳基甲酮；SHP2PTP；抑制剂；构效关系；Diaryl Ketones； SHP2； Inhibitors； Structure-Activity Relationships (SARs)
摘要: 蛋白酪氨酸磷酸酶SHP2在细胞信号转导过程中起着重要的作用，参与细胞的生长、分化、代谢、运动和凋亡，作为潜在的抗肿瘤治疗靶点备受关注。二芳基甲酮化合物在生物活性分子中广泛存在，是基于片段的药物发现策略(fragment-based drug discovery, FBDD)的理想结构模块。本试验研究了二芳基甲酮化合物在SHP2PTP模型上的构效关系，结果表明4-甲氧基二苯甲酮(1l)、(2-氟苯基)-(2-噻吩基)甲酮(1u)以及(2,4-二甲氧基苯基)-(2-氟苯基)甲酮(1v)在20 μg/mL的浓度下，对SHP2PTP分别表现了53.90% ± 8.35%、47.03% ± 4.85%和50.08% ± 3.90%的抑制率，为后续基于片段的SHP2抑制剂研究工作奠定了一定的基础。
Abstract: SHP2 is of importance for the regulation of essential cellular processes that control growth, diffe-rentiation, metabolism, motility and apoptosis and has potential as a drug target. Diaryl ketones are frequently used as core motifs for fragment-based drug discovery (FBDD). A series of diarylketones was evaluated as a new class of inhibitors against Scr homology-2 domain containing protein tyrosine phosphatase-2 (SHP2). Among them, (4-methoxyphenyl) (phenyl) methanone (1l), (2-fluorophenyl) (thiophen-2-yl) methanone (1u), (2,4-dimethoxyphenyl) (2-fluorophenyl) methanone (1v) exhibited enzyme inhibitory ratio at the dose of 20 μg/mL with 53.90% ± 8.35%, 47.03% ± 4.85% and 50.08% ± 3.90% respectively and these results would be highly advantageous for fragment-based drug discovery to obtain selective SHP2 inhibitors.
文章引用：范秋玥, 张传涛, 王文龙. 二芳基甲酮化合物抑制SHP2生物活性研究[J]. 药物化学, 2019, 7(2): 19-24. https://doi.org/10.12677/HJMCe.2019.72004

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