PKIDB: A Curated, Annotated and Updated Database of Protein Kinase Inhibitors in Clinical Trials.
PKIDB: A Curated, Annotated and Updated Database of Protein Kinase Inhibitors in Clinical Trials.
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DOI：
10.3390/molecules23040908
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发表时间：
2018-04-15
期刊：
影响因子：
--
通讯作者：
Bonnet P
中科院分区：
文献类型：
--
作者：
Carles F;Bourg S;Meyer C;Bonnet P
全球批准的蛋白激酶抑制剂（PKIs）数量继续稳步增长，2001年至2018年1月期间批准了39种药物。市场上的PKIs已经成为许多评论的主题，并且已经推断出这类药物特有的结构-性质关系。然而，正在开发的大量公用钥匙基础设施往往被忽视。在本文中，我们介绍了PKIDB（蛋白激酶抑制剂数据库），一个每月更新的数据库，收集批准的PKIs以及目前在临床试验中的PKIs。该数据库目前汇编了180种抑制剂，范围从0期到4期临床试验，沿着的是从7个公共资源中提取的注释。给出了标准物理化学性质的分布和性质范围。它们可以用作过滤器，以更好地优先考虑未来筛选活动的化合物选择。有趣的是，超过三分之一的激酶抑制剂违反至少一个Lipinski规则。主成分分析（PCA）表明，II型抑制剂被映射到一个不同的化学空间相比，口服药物以及其他类型的激酶抑制剂。使用主惯性矩（PMI）分析，我们表明，PKIs开发中倾向于探索新的形状领土相比，批准PKIs。为了便于蛋白质空间的分析，激酶组树已经用PKI靶向的所有蛋白激酶进行了注释。最后，我们分析了在市场上或仍在开发中的PKI的制药公司的管道。我们希望这项工作将有助于激酶领域的研究人员识别和设计下一代激酶抑制剂，用于仍然非靶向的激酶。公共部门工业发展数据库可从网址免费进入，并可通过方便用户的电子表格式界面轻松浏览。
The number of protein kinase inhibitors (PKIs) approved worldwide continues to grow steadily, with 39 drugs approved in the period between 2001 and January 2018. PKIs on the market have been the subject of many reviews, and structure-property relationships specific to this class of drugs have been inferred. However, the large number of PKIs under development is often overlooked. In this paper, we present PKIDB (Protein Kinase Inhibitor Database), a monthly-updated database gathering approved PKIs as well as PKIs currently in clinical trials. The database compiles currently 180 inhibitors ranging from phase 0 to 4 clinical trials along with annotations extracted from seven public resources. The distribution and property ranges of standard physicochemical properties are presented. They can be used as filters to better prioritize compound selection for future screening campaigns. Interestingly, more than one-third of the kinase inhibitors violate at least one Lipinski’s rule. A Principal Component Analysis (PCA) reveals that Type-II inhibitors are mapped to a distinct chemical space as compared to orally administrated drugs as well as to other types of kinase inhibitors. Using a Principal Moment of Inertia (PMI) analysis, we show that PKIs under development tend to explore new shape territories as compared to approved PKIs. In order to facilitate the analysis of the protein space, the kinome tree has been annotated with all protein kinases being targeted by PKIs. Finally, we analyzed the pipeline of the pharmaceutical companies having PKIs on the market or still under development. We hope that this work will assist researchers in the kinase field in identifying and designing the next generation of kinase inhibitors for still untargeted kinases. The PKIDB database is freely accessible from a website at and can be easily browsed through a user-friendly spreadsheet-like interface.
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作者：
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