Development and application of a customized online affinity selection mass spectrometry screening platform
With the evolving landscape of small molecule modalities and drug target portfolios, affinity selection mass spectrometry (ASMS) has emerged as a preferred high-throughput screening approach, driven by the growing chemical space capable of regulating historically undruggable targets. To meet the eve...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-08-01
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| Series: | SLAS Technology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2472630325000871 |
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| author | Jun Zhang Jerry Barney Qingqing Shen Anthony Paiva Wilson Shou Chris Barbieri Nancy Huynh Heidi L. Perez Andrew F. Donnell Cullen L. Cavallaro |
| author_facet | Jun Zhang Jerry Barney Qingqing Shen Anthony Paiva Wilson Shou Chris Barbieri Nancy Huynh Heidi L. Perez Andrew F. Donnell Cullen L. Cavallaro |
| author_sort | Jun Zhang |
| collection | DOAJ |
| description | With the evolving landscape of small molecule modalities and drug target portfolios, affinity selection mass spectrometry (ASMS) has emerged as a preferred high-throughput screening approach, driven by the growing chemical space capable of regulating historically undruggable targets. To meet the ever-increasing demand for binding screens, the ASMS platform requires continuous enhancements in efficiency and scalability. In this study, we developed a customized online ASMS platform, featuring multiplexed two-dimensional LC/MS for sample analysis, ultrafast acoustic ejection mass spectrometry for reaction product scouting of high-throughput chemistry before subjecting them to direct ASMS screens, and an integrated tool for real-time data processing and cross-hit evaluation. With the quality controls we implemented to ensure operational robustness and quality, the multiplexed system has demonstrated significantly enhanced analytical speed, efficiency, and overall capacity. The integrated data processing tool enhanced data quality by incorporating advanced cross-hit assessments to reduce false positives, and streamlined the screening workflow through real-time data analysis, effectively eliminating the traditional bottleneck in ASMS screening. The established ASMS platform has been utilized for our internal screening campaigns generating tractable binding hits, and providing direct affinity ranking of hits from nanoscale synthesis, enabling hit optimization and chemotype expansion with demonstrated high platform performance. |
| format | Article |
| id | doaj-art-4ad257b272b94b0bbac49df44aaf044b |
| institution | Kabale University |
| issn | 2472-6303 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | SLAS Technology |
| spelling | doaj-art-4ad257b272b94b0bbac49df44aaf044b2025-08-20T03:40:31ZengElsevierSLAS Technology2472-63032025-08-013310032910.1016/j.slast.2025.100329Development and application of a customized online affinity selection mass spectrometry screening platformJun Zhang0Jerry Barney1Qingqing Shen2Anthony Paiva3Wilson Shou4Chris Barbieri5Nancy Huynh6Heidi L. Perez7Andrew F. Donnell8Cullen L. Cavallaro9Corresponding author.; Bristol Myers Squibb, Discovery & Development Sciences, 3551 Lawrenceville Princeton Rd, Princeton, NJ 08648, USABristol Myers Squibb, Discovery & Development Sciences, 3551 Lawrenceville Princeton Rd, Princeton, NJ 08648, USABristol Myers Squibb, Discovery & Development Sciences, 3551 Lawrenceville Princeton Rd, Princeton, NJ 08648, USABristol Myers Squibb, Discovery & Development Sciences, 3551 Lawrenceville Princeton Rd, Princeton, NJ 08648, USABristol Myers Squibb, Discovery & Development Sciences, 3551 Lawrenceville Princeton Rd, Princeton, NJ 08648, USABristol Myers Squibb, Discovery & Development Sciences, 3551 Lawrenceville Princeton Rd, Princeton, NJ 08648, USABristol Myers Squibb, Discovery & Development Sciences, 3551 Lawrenceville Princeton Rd, Princeton, NJ 08648, USABristol Myers Squibb, Discovery & Development Sciences, 3551 Lawrenceville Princeton Rd, Princeton, NJ 08648, USABristol Myers Squibb, Discovery & Development Sciences, 3551 Lawrenceville Princeton Rd, Princeton, NJ 08648, USABristol Myers Squibb, Discovery & Development Sciences, 3551 Lawrenceville Princeton Rd, Princeton, NJ 08648, USAWith the evolving landscape of small molecule modalities and drug target portfolios, affinity selection mass spectrometry (ASMS) has emerged as a preferred high-throughput screening approach, driven by the growing chemical space capable of regulating historically undruggable targets. To meet the ever-increasing demand for binding screens, the ASMS platform requires continuous enhancements in efficiency and scalability. In this study, we developed a customized online ASMS platform, featuring multiplexed two-dimensional LC/MS for sample analysis, ultrafast acoustic ejection mass spectrometry for reaction product scouting of high-throughput chemistry before subjecting them to direct ASMS screens, and an integrated tool for real-time data processing and cross-hit evaluation. With the quality controls we implemented to ensure operational robustness and quality, the multiplexed system has demonstrated significantly enhanced analytical speed, efficiency, and overall capacity. The integrated data processing tool enhanced data quality by incorporating advanced cross-hit assessments to reduce false positives, and streamlined the screening workflow through real-time data analysis, effectively eliminating the traditional bottleneck in ASMS screening. The established ASMS platform has been utilized for our internal screening campaigns generating tractable binding hits, and providing direct affinity ranking of hits from nanoscale synthesis, enabling hit optimization and chemotype expansion with demonstrated high platform performance.http://www.sciencedirect.com/science/article/pii/S2472630325000871Affinity selection mass spectrometryHigh throughput screeningBinding screeningHit discoveryAffinity ranking |
| spellingShingle | Jun Zhang Jerry Barney Qingqing Shen Anthony Paiva Wilson Shou Chris Barbieri Nancy Huynh Heidi L. Perez Andrew F. Donnell Cullen L. Cavallaro Development and application of a customized online affinity selection mass spectrometry screening platform SLAS Technology Affinity selection mass spectrometry High throughput screening Binding screening Hit discovery Affinity ranking |
| title | Development and application of a customized online affinity selection mass spectrometry screening platform |
| title_full | Development and application of a customized online affinity selection mass spectrometry screening platform |
| title_fullStr | Development and application of a customized online affinity selection mass spectrometry screening platform |
| title_full_unstemmed | Development and application of a customized online affinity selection mass spectrometry screening platform |
| title_short | Development and application of a customized online affinity selection mass spectrometry screening platform |
| title_sort | development and application of a customized online affinity selection mass spectrometry screening platform |
| topic | Affinity selection mass spectrometry High throughput screening Binding screening Hit discovery Affinity ranking |
| url | http://www.sciencedirect.com/science/article/pii/S2472630325000871 |
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