Chemical biology of compounds obtained from screening using disease models
Chemical biology of compounds obtained from screening using disease models
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使用疾病模型筛选获得的化合物的化学生物学
DOI：
10.1007/s12272-015-0633-4
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Imoto M.
中科院分区：
文献类型：
--
作者：
Tashiro E;Imoto M.
生物活性化合物是研究生物系统的非常强大的工具，因为它们可以快速，有条件地，经常可逆地和剂量依赖性地调节活细胞的生物功能。此外，它们有望成为多种疾病化疗的药物种子。发现和获得生物活性化合物有两种方法，即基于分子靶标的筛选和表型筛选。通过模拟肿瘤转移、多药耐药性和帕金森病的表型筛选，我们鉴定了几种抑制癌细胞迁移、Bcl-2/Bcl-xL的抗凋亡功能和神经元细胞死亡的化合物。通过靶向筛选开发的MEK抑制剂，我们发现MEK抑制剂选择性地诱导β-catenin突变的肿瘤细胞凋亡。利用靶向筛选，我们确定了arabilin，一种新的雄激素拮抗剂。本文介绍了近年来通过表型筛选和靶点筛选发现具有生物活性的化合物的研究进展。
Bioactive compounds are extremely powerful tools for studying biological systems because they can rapidly, conditionally, often reversibly, and dose-dependently modulate the biological function of living cells. Moreover, they are expected to be drug seeds for chemotherapy of several diseases. Two approaches are used to find and obtain bioactive compounds, namely, molecular-target-based screening and phenotypic screening. Through phenotypic screening that mimics tumor metastasis, multi-drug resistance, and Parkinson’s disease, we identified several compounds that inhibit cancer cell migration, anti-apoptotic function of Bcl-2/Bcl-xL, and neuronal cell death. By using MEK inhibitor that was developed by target-based screening, we discovered that MEK inhibitor selectively induces apoptosis in tumor cells with β-catenin mutation. Using target-based screening, we identified arabilin, a novel androgen antagonist. In this review, we introduce our recent studies on the identification of bioactive compounds by phenotypic screening and by target-based screening for drug-seed discovery.