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Drug Target Mining and Analysis of the Chinese Tree Shrew for Pharmacological Testing

机译:中国树Sh药理试验药物靶点的挖掘与分析

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摘要

The discovery of new drugs requires the development of improved animal models for drug testing. The Chinese tree shrew is considered to be a realistic candidate model. To assess the potential of the Chinese tree shrew for pharmacological testing, we performed drug target prediction and analysis on genomic and transcriptomic scales. Using our pipeline, 3,482 proteins were predicted to be drug targets. Of these predicted targets, 446 and 1,049 proteins with the highest rank and total scores, respectively, included homologs of targets for cancer chemotherapy, depression, age-related decline and cardiovascular disease. Based on comparative analyses, more than half of drug target proteins identified from the tree shrew genome were shown to be higher similarity to human targets than in the mouse. Target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets. We developed an effective pipeline and search strategy for drug target prediction and the evaluation of model-based target identification for drug testing. This work provides useful information for future studies of the Chinese tree shrew as a source of novel targets for drug discovery research.
机译:新药的发现需要开发用于药物测试的改良动物模型。中国树sh被认为是一种现实的候选模型。为了评估sh树进行药理测试的潜力,我们在基因组和转录组学规模上进行了药物靶标预测和分析。使用我们的产品线,预计3,482种蛋白质将成为药物靶标。在这些预测的靶标中,具有最高等级和总分的446和1,049蛋白分别包括癌症化学疗法,抑郁症,与年龄相关的衰弱和心血管疾病的靶标同源物。根据比较分析,从树sh基因组中鉴定出的一半以上的药物靶蛋白与人类靶标的相似性高于小鼠。目标验证还表明,树sh血小板的蛋白酶激活受体的组成性表达与人血小板相似,但与小鼠血小板不同。我们开发了有效的管道和搜索策略,用于药物靶标预测和评估基于模型的药物鉴定靶标。这项工作为今后对中国sh树的研究提供了有用的信息,作为药物发现研究的新靶标。

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