{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:45:45Z","timestamp":1792140345865,"version":"4.4.0"},"reference-count":72,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021821","name":"Oncode Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021821","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Oncode Accelerator","award":["NGFOP2201"],"award-info":[{"award-number":["NGFOP2201"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Activity-based protein profiling has established itself as a powerful technology with demonstrated use in on- and off-target profiling. However, determining the off-target profile of many drugs using the unbiased mass spectrometry-based chemoproteomics approach remains time- and cost-intensive. In this study, we implemented an SP3-based, high-throughput, plate-based chemoproteomic workflow compatible with liquid-handling robotics. We then profiled a library of 40 marketed drugs targeting the serine hydrolases or containing potentially reactive electrophiles against the human serine hydrolase proteome in HT29 cell lysate. We included two additional well-studied literature compounds as controls to benchmark our workflow. Our results validated 16 out of 20 intended human targets and found 5 previously described off-targets for the compounds tested. Additionally, we discovered six unknown off-targets that could warrant future follow-up research. In all, our approach demonstrates how automated chemoproteomics can be used to accelerate the identification of clinically relevant off-targets, providing a scalable blueprint for rational drug repurposing.<\/jats:p>","DOI":"10.1021\/acschembio.6c00557","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:01:28Z","timestamp":1789023688000},"page":"2683-2694","source":"Crossref","is-referenced-by-count":0,"title":["An Automated Scalable Chemoproteomics Workflow that Recovers Known Serine Hydrolase Target Profiles of Clinically Used Drugs"],"prefix":"10.1021","volume":"21","author":[{"given":"Franciscus H.G.","family":"ter Brake","sequence":"first","affiliation":[{"name":"Leiden University , , ,","place":["Leiden, The Netherlands, 2300 RA"]},{"name":"Oncode Institute , ,","place":["Utrecht, The Netherlands, 3521 AL"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berend","family":"Gagestein","sequence":"additional","affiliation":[{"name":"Leiden University , , ,","place":["Leiden, The Netherlands, 2300 RA"]},{"name":"Oncode Institute , ,","place":["Utrecht, The Netherlands, 3521 AL"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1029-5717","authenticated-orcid":true,"given":"Mario","family":"van der Stelt","sequence":"additional","affiliation":[{"name":"Leiden University , , ,","place":["Leiden, The Netherlands, 2300 RA"]},{"name":"Oncode Institute , ,","place":["Utrecht, The Netherlands, 3521 AL"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4203-261X","authenticated-orcid":true,"given":"Antonius P.A.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Leiden University , , ,","place":["Leiden, The Netherlands, 2300 RA"]},{"name":"Oncode Institute , ,","place":["Utrecht, The Netherlands, 3521 AL"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"issue":"7","key":"2026101523062966400_cit1","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/nrd4609","article-title":"An Analysis of the Attrition of Drug Candidates from Four Major Pharmaceutical Companies","volume":"14","author":"Waring","year":"2015","journal-title":"Nat. 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