Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA.
ApconiX Ltd, Alderley Park, Alderley Edge, SK10 4TG, UK; University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Drug Discov Today. 2020 Jan;25(1):201-208. doi: 10.1016/j.drudis.2019.09.022. Epub 2019 Nov 1.
Drug-induced liver injury (DILI) is of significant concern to drug development and regulatory review because of the limited success with existing preclinical models. For developing alternative methods, a large drug list is needed with known DILI severity and toxicity. We augmented the DILIrank data set [annotated using US Food and Drug Administration (FDA) drug labeling)] with four literature datasets (N >350 drugs) to generate the largest drug list with DILI classification, called DILIst (DILI severity and toxicity). DILIst comprises 1279 drugs, of which 768 were DILI positives (increase of 65% from DILIrank), whereas 511 were DILI negatives (increase of 65%). The investigation of DILI positive-negative distribution across various therapeutic categories revealed the most and least frequent DILI categories. Thus, we consider DILIst to be an invaluable resource for the community to improve DILI research.
药物性肝损伤(DILI)是药物开发和监管审查的一个重要关注点,因为现有的临床前模型成功率有限。为了开发替代方法,需要有一个包含已知 DILI 严重程度和毒性的大型药物清单。我们用四个文献数据集(N>350 种药物)扩充了 DILIrank 数据集(使用美国食品和药物管理局(FDA)药物标签进行注释),生成了一个最大的带有 DILI 分类的药物清单,称为 DILIst(DILI 严重程度和毒性)。DILIst 包含 1279 种药物,其中 768 种是 DILI 阳性(比 DILIrank 增加了 65%),而 511 种是 DILI 阴性(比 DILIrank 增加了 65%)。对不同治疗类别中 DILI 阳性和阴性分布的研究揭示了最常见和最不常见的 DILI 类别。因此,我们认为 DILIst 是一个宝贵的资源,可供社区用于改进 DILI 研究。