{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T12:29:44Z","timestamp":1774441784528,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,22]]},"group-title":"Pharmacology and Toxicology","reference-count":35,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T00:00:00Z","timestamp":1774137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["UID\/04138\/2025 (doi: 10.54499\/UID\/04138\/2025)"],"award-info":[{"award-number":["UID\/04138\/2025 (doi: 10.54499\/UID\/04138\/2025)"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2022.07857.PTDC"],"award-info":[{"award-number":["2022.07857.PTDC"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"award":["SFRH\/BD\/137459\/2018"],"award-info":[{"award-number":["SFRH\/BD\/137459\/2018"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"award":["COVID\/BD\/153228\/2023"],"award-info":[{"award-number":["COVID\/BD\/153228\/2023"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"award":["European Union\u2019s Horizon Europe Programme under grant agreement No 101132028, project IMPULSE"],"award-info":[{"award-number":["European Union\u2019s Horizon Europe Programme under grant agreement No 101132028, project IMPULSE"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Human Neutrophil Elastase (HNE) plays a vital role in several inflammatory diseases, however its role in the tumour microenvironment and the potential in cancer treatment is still unrevealed. Considering the potential of\n                  <jats:italic>\u03b2<\/jats:italic>\n                  -lactams as HNE inhibitors, the present work describes the development of a synthetic strategy to obtain two different types (Type I and Type II) of quenched activity-based probes (qABPs), using a\n                  <jats:italic>\u03b2<\/jats:italic>\n                  -lactam ring as a warhead and BODIPY-FL as a fluorophore. The two types differ in mechanism and relative position between the fluorophore and the quencher moiety. The qABPs synthesized presented IC\n                  <jats:sub>50<\/jats:sub>\n                  values against HNE lower than 0.5\n                  <jats:italic>\u00b5<\/jats:italic>\n                  M, and high selectivity compared with homologous serine hydrolases. Type II qABPs showed a more efficient turn-on mechanism, and selectively targeted HNE in different cell lysates. The qABP\n                  <jats:bold>22<\/jats:bold>\n                  was internalized in U937 cells and in human neutrophils and successfully targeted HNE in both.\n                <\/jats:p>","DOI":"10.64898\/2026.03.19.712884","type":"posted-content","created":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T23:45:14Z","timestamp":1774223114000},"source":"Crossref","is-referenced-by-count":0,"title":["BODIPY-Tagged\n                  <i>\u03b2<\/i>\n                  -Lactams as Selective Quenched Activity-Based Probes to Target Human Neutrophil Elastase"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7192-0822","authenticated-orcid":false,"given":"Rita","family":"F\u00e9lix","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa. Lisboa, Portugal"},{"name":"Faculty of Pharmacy, Universidade de Lisboa. Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5257-7301","authenticated-orcid":false,"given":"Lu\u00eds A. R.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, 1 Midland Road, London NW1 1AT, United Kingdom"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5790-9181","authenticated-orcid":false,"given":"Rita","family":"Guedes","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa. Lisboa, Portugal"},{"name":"Faculty of Pharmacy, Universidade de Lisboa. Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5973-2183","authenticated-orcid":false,"given":"Ana Margarida","family":"Madureira","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa. Lisboa, Portugal"},{"name":"Faculty of Pharmacy, Universidade de Lisboa. Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5092-3538","authenticated-orcid":false,"given":"Ana","family":"Mallo-Abreu","sequence":"additional","affiliation":[{"name":"Centro Singular de Investigaci\u00f3n en Qu\u00edmica Biol\u00f3xica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultade de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6799-2740","authenticated-orcid":false,"given":"L\u00eddia","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa. Lisboa, Portugal"},{"name":"Faculty of Pharmacy, Universidade de Lisboa. Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4202-1219","authenticated-orcid":false,"given":"Olga","family":"Genilloud","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n MEDINA, Av. Conocimiento 34, Health Sciences Technology Park, 18016 Granada, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8831-7189","authenticated-orcid":false,"given":"Rosario","family":"Fernandez-Godino","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n MEDINA, Av. Conocimiento 34, Health Sciences Technology Park, 18016 Granada, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3674-615X","authenticated-orcid":false,"given":"Maria C","family":"Ramos","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n MEDINA, Av. Conocimiento 34, Health Sciences Technology Park, 18016 Granada, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0727-9852","authenticated-orcid":false,"given":"Rui","family":"Moreira","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa. Lisboa, Portugal"},{"name":"Faculty of Pharmacy, Universidade de Lisboa. Lisboa, Portugal"}]}],"member":"54368","reference":[{"issue":"3-4","key":"2026032502400994000_2026.03.19.712884v1.1","doi-asserted-by":"crossref","first-page":"e202300016","DOI":"10.1002\/ijch.202300016","article-title":"Serine Hydrolase Activity-Based Probes for Use in Chemical Proteomics","volume":"63","year":"2023","journal-title":"Israel Journal of Chemistry"},{"key":"2026032502400994000_2026.03.19.712884v1.2","doi-asserted-by":"crossref","unstructured":"Jin Q , Song L-L , Ding L-L , Zhang J , Wang D-D , Song Y-Q , et al. 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