Small Molecule Libraries
The discovery of bioactive small molecules is generally driven via iterative design-make-purify-test cycles. Automation is nowadays routinely used at the purify and test stage of these cycles but still very rarely at the design and make stage. However, recent advances in areas such as microfluidics-assisted and batch chemical synthesis as well as AI systems that improve a design hypothesis through feedback analysis, are now providing a basis for the introduction of greater automation into all aspects of this process.
Here, we describe recent progress we have made with the build of a fully automated synthesis platform comprising all aspects of the make-purify workflow. A variety of chemistry transformations have been established on the platform allowing not only the rapid synthesis of compound libraries but also complex molecules via multistep sequences. The value and impact of our platform is illustrated in the context of specific case studies from the early phase drug discovery.
We also consider the longer-term goal of realizing the fully autonomous discovery of bioactive small molecules through the integration of our automated synthesis platform with automated design and testing.