Quantifying, Visualizing, and Monitoring Lead Optimization

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• 作者：Andrew T. Maynard ; Christopher D. Roberts
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：May 12, 2016
• 年：2016
• 卷：59
• 期：9
• 页码：4189-4201
• 全文大小：892K
• 年卷期：0
• ISSN：1520-4804

文摘

Although lead optimization (LO) is by definition a process, process-centric analysis and visualization of this important phase of pharmaceutical R&D has been lacking. Here we describe a simple statistical framework to quantify and visualize the progression of LO projects so that the vital signs of LO convergence can be monitored. We refer to the resulting visualizations generated by our methodology as the “LO telemetry” of a project. These visualizations can be automated to provide objective, holistic, and instantaneous analysis and communication of LO progression. This enhances the ability of project teams to more effectively drive LO process, while enabling management to better coordinate and prioritize LO projects. We present the telemetry of five LO projects comprising different biological targets and different project outcomes, including clinical compound selection, termination due to preclinical safety/tox, and termination due to lack of tractability. We demonstrate that LO progression is accurately captured by the telemetry. We also present metrics to quantify LO efficiency and tractability.