A high-throughput screening assay for mutant isocitrate dehydrogenase 1 using acoustic droplet ejection mass spectrometry

• DOI: 10.1016/j.slasd.2022.04.002
• Publication Date: 2022-04-20T21:40:15Z
• Authors: Elisabeth Speckmeier; Antje Pommereau; Kay-Christoph Gro...; Hartmut Mors; Thomas C. Maier; Thomas Licher; Felix Bärenz
• Keywords: Isocitrate dehydrogenase; High-Throughput Screening

Acoustic droplet ejection mass spectrometry (ADE-MS) has recently emerged as a promising label-free, MS-based readout method for high throughput screening (HTS) campaigns in early pharmaceutical drug discovery, since it enables high-speed analysis directly from 384- or 1536-well plates. In this manuscript we describe our characterization of an ADE-MS based sample content enzymatic assay mutant isocitrate dehydrogenase 1 (IDH1) R132H with strong focus on development. IDH1 become very attractive therapeutic target the field antitumor and several companies have attempted to develop novel small molecule inhibitors against IDH1. With development mIDH1 HTS detailed comparison new technique commonly used fluorescence intensity assay, demonstrated good correlation both methods were able identify potent mIDH1.