2026-06-17 パデュー大学
＜関連情報＞
- https://www.purdue.edu/newsroom/2026/Q2/purdue-researchers-work-to-accelerate-cancer-drug-discovery-with-next-gen-tech-platform/
- https://www.pnas.org/doi/10.1073/pnas.2536552123
新世代超高スループット質量分析プラットフォームを用いた初期段階の創薬 Early-stage drug discovery in a new-generation ultrahigh-throughput mass spectrometry platform
Nicolás M. Morato, Yunfei Feng, Kitmin Chen, +17 , and R. Graham Cooks
Proceedings of the National Academy of Sciences Published:June 2, 2026
DOI;https://doi.org/10.1073/pnas.2536552123
Significance
Drug discovery requires both synthesis and bioactivity testing of a vast number of compounds. However, the scale and speed at which these two operations have been carried out historically are significantly mismatched, with efforts toward making new molecules typically running way behind those focused on testing them. Here we describe an automated system that addresses this bottleneck by combining reaction screening, small-scale synthesis, and bioactivity assessment with matched throughputs. This consolidation is achieved by leveraging accelerated microdroplet reactions and ambient mass spectrometry together with automated robotics and data analysis. In this work, we provide an overview of the design and construction of this system, illustrate its capabilities across the drug discovery pipeline, and present a perspective on its wider applicability.
Abstract
Early-stage drug discovery involves a complex set of processes that typically requires iterative exploration of a vast chemical-biological search space. Over the past few decades, these processes have been facilitated using automated experimentation in the form of high-throughput screening technologies for hit discovery via large-scale biochemical assays of candidate libraries. However, optimized generation of small-molecule candidates is still largely limited to traditional synthetic chemistry workflows, thus representing a bottleneck in the discovery endeavor. Here we describe and demonstrate the capabilities of a next-generation automated ultrahigh-throughput system based on desorption electrospray ionization (DESI) mass spectrometry (MS), which consolidates key activities of early drug discovery: i) organic reaction screening for routes to new candidates, ii) small-scale synthesis following optimized reactions, and iii) bioactivity assessment of the newly generated compounds in a direct-to-biology (i.e., product purification-free) fashion. Importantly, the first two synthetic steps leverage accelerated reactions in microdroplets for on-the-fly synthesis followed by in operando MS analysis or small-scale collection, whereas the later bioanalytical application relies on the label-free nature of MS as well as the contactless and complex-matrix-tolerant nature of DESI. Altogether, this fully automated technology, which has a combined synthetic/analytical throughput of up to ~3 Hz using (sub)nanogram sample amounts (and ca. 6 mHz at the milligram-level synthetic scale), has the potential to accelerate translational efforts via a single-platform closed-loop discovery cycle whose main aspects are illustrated herein, including the demonstration of increases in the biological activity of drug-substance analogs generated in the course of a complete DESI-based direct-to-biology campaign.
