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Therefore, cancer cells are sensitive to drugs capable of further enhancing ER stress. Examples of such drugs include the clinically approved proteosome inhibitors bortezomib and carfilzomib. Unfortunately, the known ER stress inducers exhibit dose-limiting side effects that justify the search for better, more cancer-specific drugs of this type. Herein, we report on FeC 2, which binds to unfolded proteins prevents their further processing, thereby leading to ER stress and ROS increase in cancer cells, but not in normal cells. FeC 2 exhibits low micromolar toxicity toward human acute promyelocytic leukemia HL-60, Burkitt\u2019s lymphoma BL-2, T-cell leukemia Jurkat, ovarian carcinoma A2780, lung cancer SK-MES-1, and murine lung cancer LLC1 cells. Due to the cancer-specific mode of action, 2 is not toxic in vivo up to the dose of 147 mg\/kg, does not affect normal blood and bone marrow cells at the therapeutically active dose, but strongly suppresses both primary tumor growth (confirmed in Nemeth-Kellner lymphoma and LLC1 lung cancer models of murine tumor) and spreading of metastases (LLC1).<\/jats:p>","DOI":"10.1021\/jacs.3c08827","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T11:06:20Z","timestamp":1695985580000},"page":"22252-22264","source":"Crossref","is-referenced-by-count":17,"title":["3D-Shaped\nBinders of Unfolded Proteins Inducing Cancer\nCell-Specific Endoplasmic Reticulum Stress In Vitro and In Vivo"],"prefix":"10.1021","volume":"145","author":[{"given":"Insa","family":"Klemt","sequence":"first","affiliation":[{"name":"Friedrich-Alexander-University of Erlangen-Nu\u0308rnberg (FAU) , , ,","place":["Erlangen, Germany, 91058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Varzatskii","sequence":"additional","affiliation":[{"name":"Princeton Biomolecular Research Laboratories , 26A Saperne Pole Street , ,","place":["Kyiv, Ukraine, 01042"]},{"name":"NASU , , 32\/34 Palladin Av. , ,","place":["Kyiv, Ukraine, 03142"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Selin","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University of Erlangen-Nu\u0308rnberg (FAU) , , ,","place":["Erlangen, Germany, 91058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serhii","family":"Vakarov","sequence":"additional","affiliation":[{"name":"Princeton Biomolecular Research Laboratories , 26A Saperne Pole Street , ,","place":["Kyiv, Ukraine, 01042"]},{"name":"NASU , , 32\/34 Palladin Av. , ,","place":["Kyiv, Ukraine, 03142"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladyslava","family":"Kovalska","sequence":"additional","affiliation":[{"name":"Princeton Biomolecular Research Laboratories , 26A Saperne Pole Street , ,","place":["Kyiv, Ukraine, 01042"]},{"name":"Institute of Molecular Biology and Genetics, NASU , 150 Zabolotnogo Street , ,","place":["Kyiv, Ukraine, 03143"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galyna","family":"Bila","sequence":"additional","affiliation":[{"name":"Danylo Halytsky Lviv National Medical University , , Pekarska Street 69 , ,","place":["Lviv, Ukraine, 79010"]},{"name":"Lectinotest R&D , Mechanichna Street 2 , ,","place":["Lviv, Ukraine, 79024"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2344-1349","authenticated-orcid":true,"given":"Rostyslav","family":"Bilyy","sequence":"additional","affiliation":[{"name":"Danylo Halytsky Lviv National Medical University , , Pekarska Street 69 , ,","place":["Lviv, Ukraine, 79010"]},{"name":"Lectinotest R&D , Mechanichna Street 2 , ,","place":["Lviv, Ukraine, 79024"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2823-6560","authenticated-orcid":true,"given":"Yan","family":"Voloshin","sequence":"additional","affiliation":[{"name":"RAS , , 28 Vavilova Street , ,","place":["Moscow, Russia, 119334"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itziar Cossi\u0301o","family":"Cuartero","sequence":"additional","affiliation":[{"name":"Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) , , C. 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