The discovery of bioactive small molecules is generally driven via iterative design–make–purify–test cycles. Automation is routinely harnessed at individual stages of these cycles to increase the productivity of drug discovery. Here, we describe recent progress to automate and integrate two or more adjacent stages within discovery workflows. Examples of such technologies include microfluidics, liquid-handling robotics and affinity-selection mass spectrometry. The value of integrated technologies is illustrated in the context of specific case studies in which modulators of targets, such as protein kinases, nuclear hormone receptors and protein–protein interactions, were discovered. We note that to maximize impact on the productivity of discovery, each of the integrated stages would need to have both high and matched throughput. We also consider the longer-term goal of realizing the fully autonomous discovery of bioactive small molecules through the integration and automation of all stages of discovery.

生物活性小分子的发现通常是通过反复的设计，制造，纯化和测试循环来推动的。在这些周期的各个阶段，通常会利用自动化来提高药物发现的生产率。在这里，我们描述了在发现工作流程中自动化和集成两个或多个相邻阶段的最新进展。这种技术的例子包括微流体技术，液体处理机器人技术和亲和力选择质谱法。在特定案例研究的背景下说明了集成技术的价值，在该案例研究中发现了靶标调节剂，例如蛋白激酶，核激素受体和蛋白-蛋白相互作用。我们注意到，为了最大程度地提高发现效率，每个集成阶段都需要具有高吞吐量和匹配的吞吐量。