* Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079;
Toxicol Sci. 2013 Oct;135(2):277-91. doi: 10.1093/toxsci/kft164. Epub 2013 Jul 28.
Endocrine-active chemicals can potentially have adverse effects on both humans and wildlife. They can interfere with the body's endocrine system through direct or indirect interactions with many protein targets. Estrogen receptors (ERs) are one of the major targets, and many endocrine disruptors are estrogenic and affect the normal estrogen signaling pathways. However, ERs can also serve as therapeutic targets for various medical conditions, such as menopausal symptoms, osteoporosis, and ER-positive breast cancer. Because of the decades-long interest in the safety and therapeutic utility of estrogenic chemicals, a large number of chemicals have been assayed for estrogenic activity, but these data exist in various sources and different formats that restrict the ability of regulatory and industry scientists to utilize them fully for assessing risk-benefit. To address this issue, we have developed an Estrogenic Activity Database (EADB; http://www.fda.gov/ScienceResearch/BioinformaticsTools/EstrogenicActivityDatabaseEADB/default.htm) and made it freely available to the public. EADB contains 18,114 estrogenic activity data points collected for 8212 chemicals tested in 1284 binding, reporter gene, cell proliferation, and in vivo assays in 11 different species. The chemicals cover a broad chemical structure space and the data span a wide range of activities. A set of tools allow users to access EADB and evaluate potential endocrine activity of chemicals. As a case study, a classification model was developed using EADB for predicting ER binding of chemicals.
内分泌活性化学物质可能对人类和野生动物都有不良影响。它们可以通过与许多蛋白质靶标直接或间接相互作用，干扰身体的内分泌系统。雌激素受体 (ER) 是主要靶标之一，许多内分泌干扰物具有雌激素特性，并影响正常的雌激素信号通路。然而，ER 也可以作为各种医学病症的治疗靶点，如更年期症状、骨质疏松症和 ER 阳性乳腺癌。由于数十年来人们一直关注雌激素类化学物质的安全性和治疗效用，因此已经对大量化学物质进行了雌激素活性检测，但这些数据存在于各种来源和不同格式中，限制了监管和行业科学家充分利用这些数据来评估风险-收益的能力。为了解决这个问题，我们开发了一个雌激素活性数据库 (EADB；http://www.fda.gov/ScienceResearch/BioinformaticsTools/EstrogenicActivityDatabaseEADB/default.htm)，并免费向公众开放。EADB 包含 18114 个雌激素活性数据点，这些数据是为 8212 种化学物质在 11 个不同物种的 1284 个结合、报告基因、细胞增殖和体内测定中收集的，这些化学物质涵盖了广泛的化学结构空间，数据涵盖了广泛的活性范围。一组工具允许用户访问 EADB 并评估化学物质的潜在内分泌活性。作为一个案例研究，使用 EADB 开发了一个用于预测化学物质与 ER 结合的分类模型。
