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However, no LY\u2010targeting drug is clinically approved yet. We describe in this paper a new therapeutic approach based on alkylation of lysosomal thiols in cancer cells by reversible thiol binder <jats:bold>11<\/jats:bold>. The treatment with <jats:bold>11<\/jats:bold> increases the level of lysosomal reactive oxygen species leading to their destabilization, disruption and immunogenic cancer cell death. These effects are not observed in healthy cells. In murine sarcoma Nemeth\u2010Kellner (NK)\/Ly\u2010RB model, <jats:bold>11<\/jats:bold> exhibits the spectacular therapeutic effect: it extends the lifespan of the treated mice from 21 to 85\u2005days and cures 40\u2009% of mice. The survived mice develop antibodies against tumor NK\/Ly\u2010RB cells. Their repeated challenge with the NK\/Ly\u2010RB cells results in 100\u2009% mice survival compared to 0\u2009% survival in the control group of na\u00efve mice. Ex vivo data indicate that neutrophils in spleen of the cured animals are also involved in targeting cancer cells and produce neutrophil extracellular traps. In summary, <jats:bold>11<\/jats:bold> induces the direct antitumor effect supported by humoral immune responses, as well as priming neutrophil's reaction against tumors.<\/jats:p>","DOI":"10.1002\/anie.202417509","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T15:43:59Z","timestamp":1730735039000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Targeting Lysosomal Thiols for Immunogenic Cancer Cell Death"],"prefix":"10.1002","volume":"64","author":[{"given":"Anton","family":"Arkhypov","sequence":"first","affiliation":[{"name":"Friedrich-Alexander-University of Erlangen-N\u00fcrnberg (FAU) Department of Chemistry and Pharmacy, Organic Chemistry II  91058 Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Insa","family":"Klemt","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University of Erlangen-N\u00fcrnberg (FAU) Department of Chemistry and Pharmacy, Organic Chemistry II  91058 Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galyna","family":"Bila","sequence":"additional","affiliation":[{"name":"Danylo Halytsky Lviv National Medical University Department of Histology, Cytology and Embryology  79010 Lviv Ukraine"},{"name":"Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d, 8 B.P.Hasdeu street, Sector 5  Bucharest Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Attia","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University of Erlangen-N\u00fcrnberg (FAU) Department of Chemistry and Pharmacy, Organic Chemistry II  91058 Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svitlana","family":"Chernii","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University of Erlangen-N\u00fcrnberg (FAU) Department of Chemistry and Pharmacy, Organic Chemistry II  91058 Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rostyslav","family":"Bilyy","sequence":"additional","affiliation":[{"name":"Danylo Halytsky Lviv National Medical University Department of Histology, Cytology and Embryology  79010 Lviv Ukraine"},{"name":"Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d, 8 B.P.Hasdeu street, Sector 5  Bucharest Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9079-5569","authenticated-orcid":false,"given":"Andriy","family":"Mokhir","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University of Erlangen-N\u00fcrnberg (FAU) Department of Chemistry and Pharmacy, Organic Chemistry II  91058 Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,19]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc749"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra043186"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1009-1149"},{"key":"e_1_2_9_4_1","unstructured":"\u00a0"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.08.009"},{"issue":"3","key":"e_1_2_9_6_2","first-page":"794","volume":"51","author":"Szatrowski T. 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