The Microphysiology Systems Database for Analyzing and Modeling Compound Interactions with Human and Animal Organ Models.
The Microphysiology Systems Database for Analyzing and Modeling Compound Interactions with Human and Animal Organ Models.
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DOI：
10.1089/aivt.2016.0011
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发表时间：
2016-06-01
影响因子：
--
通讯作者：
Taylor, D Lansing
中科院分区：
文献类型：
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作者：
Gough, Albert;Vernetti, Lawrence;Taylor, D Lansing
微流体人体器官模型，微生理学系统（MPS），目前正在开发的药物安全性和有效性在人类的预测模型。为了设计和验证MPS作为人体安全性责任的预测，需要参考化合物集的安全性数据，以及来自人体器官模型的体外数据。为了满足这一需求，我们开发了一个互联网数据库，MPS数据库（MPS-Db），作为一个强大的平台，实验设计，数据管理和分析，并结合联合收割机的实验数据与参考数据，使计算建模。本研究证明了MPS-Db在使用人肝MPS的早期安全性测试中将托卡朋和恩他卡朋在体外模型中的作用与人体内作用相关联的能力。选择这两种化合物作为一对代表性的上市药物进行评价，因为它们结构相似，具有相同的靶点，并且在临床前和临床试验中发现安全或具有可接受的风险，但托卡朋诱导了不可接受的肝毒性水平，而恩他卡朋被发现是安全的。结果表明，实用程序的MPS-Db作为一个重要的资源，在体外器官模型数据的多个生物化学，临床前和临床数据源在体内药物作用。
Microfluidic human organ models, microphysiology systems (MPS), are currently being developed as predictive models of drug safety and efficacy in humans. To design and validate MPS as predictive of human safety liabilities requires safety data for a reference set of compounds, combined with in vitro data from the human organ models. To address this need, we have developed an internet database, the MPS database (MPS-Db), as a powerful platform for experimental design, data management, and analysis, and to combine experimental data with reference data, to enable computational modeling. The present study demonstrates the capability of the MPS-Db in early safety testing using a human liver MPS to relate the effects of tolcapone and entacapone in the in vitro model to human in vivo effects. These two compounds were chosen to be evaluated as a representative pair of marketed drugs because they are structurally similar, have the same target, and were found safe or had an acceptable risk in preclinical and clinical trials, yet tolcapone induced unacceptable levels of hepatotoxicity while entacapone was found to be safe. Results demonstrate the utility of the MPS-Db as an essential resource for relating in vitro organ model data to the multiple biochemical, preclinical, and clinical data sources on in vivo drug effects.