Safety Data Mining Based on Chemical Structures

描述（由申请人提供）：预测和了解药物在人体中的毒性仍然是新药开发项目的主要障碍。对于应对这一挑战，已上市药物自发不良事件报告的药物警戒数据库是人类毒性信息的重要来源，特别是如果这些数据库中确定的各种不良事件（毒性类型）与特定药物之间的关联可以根据不良事件与药物潜在化学结构的关系来理解。在第一阶段，重点是将结构化学信息整合到申请人现有的“‘WEBVDME ’安全性数据挖掘系统中，以支持对药物毒性谱（以自发不良事件数据表示）与潜在化学结构和子结构（2d片段）之间关系的初步调查。第二阶段还将研究整合其他类型信息（3-D分子描述符、药代动力学和代谢参数）的可行性和价值，以进一步阐明药物毒性的模式和问题。该项目对公共卫生的主要好处是提高了预测药物毒性的能力，从而大大减少了药物开发的财务和人力成本，并改善了进入市场的药物的安全性。

DESCRIPTION (provided by applicant): Predicting and understanding drug toxicity in humans remains a major obstacle to new drug development programs. Pharmacovigilance databases of spontaneous adverse event reports from marketed drugs represent an important source of human toxicity information for addressing this challenge, especially if the associations identified in these databases between various adverse events (types of toxicity) and specific drugs can be understood in terms of the relationship of the adverse events to the underlying chemical structure of the drugs. In Phase I, the focus is on the integration of structural chemistry information into the applicant's existing "'WEBVDME" safety data mining system to support initial investigation of relationships between drug toxicity Profiles (as expressed in spontaneous adverse event data) and underlying chemical structures and substructures (2-D fragments). Phase II will also investigate the feasibility and value of incorporating other types of information (3-D molecular descriptors, pharmacokinetic and metabolic parameters) for further elucidation of patterns and issues in drug toxicity. The key benefit of the project to public health is an improved ability to predict drug toxicity, leading to significant reductions in the financial and human costs of drug development and to improved safety profiles for the drugs that reach the market.