{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:31:11Z","timestamp":1791261071142,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T00:00:00Z","timestamp":1567555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>We identified novel dicarboximides that were selectively cytotoxic towards human leukemia cells. Using chemical and biological methods, we characterized the biological activity, identified cellular protein targets and defined the mechanism of action of the test dicarboximides. The reported IC50 values (concentration required to reduce cell survival fraction to 50% of control) of selected dicarboximides were similar or lower than IC50 of registered anticancer drugs, for example cytarabine, sorafenib, irinotecan. Test compounds induced apoptosis in chronic myelogenous (K562) and acute lymphoblastic (MOLT-4) leukemia cells by activation of receptor and mitochondrial apoptotic pathways and increased the expression of proapoptotic genes (BAX, NOXA, HTRA2, TNFRSF10B, ESRRBL1). Selected dicarboximides displayed immunomodulatory activity and downregulated IKZF1 and IKZF3 transcription factors in K562 and MOLT-4 leukemia cells. ATP-binding cassette protein 50 (ABC50) was identified as a target for dicarboximides. Cancer cells with knocked down ABC50 showed increased resistance to dicarboximides. Based on the structure of dicarboximides and thalidomide, novel proteolysis-targeting chimeras (PROTACs) were synthesized and used as tools to downregulate ABC50 in leukemia cells.<\/jats:p>","DOI":"10.3390\/biom9090446","type":"journal-article","created":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T03:22:36Z","timestamp":1567653756000},"page":"446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["New Thalidomide-Resembling Dicarboximides Target ABC50 Protein and Show Antileukemic and Immunomodulatory Activities"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9628-214X","authenticated-orcid":false,"given":"Marcin","family":"Cie\u015blak","sequence":"first","affiliation":[{"name":"Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, 112 Sienkiewicza Str., 90-363 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Ka\u017amierczak-Bara\u0144ska","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, 112 Sienkiewicza Str., 90-363 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Kr\u00f3lewska-Goli\u0144ska","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, 112 Sienkiewicza Str., 90-363 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1174-2208","authenticated-orcid":false,"given":"Mariola","family":"Napi\u00f3rkowska","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Medical University of Warsaw, 3 Oczki Str., 02-007 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iga","family":"Stukan","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urszula","family":"Wojda","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4084-4334","authenticated-orcid":false,"given":"Barbara","family":"Nawrot","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, 112 Sienkiewicza Str., 90-363 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,4]]},"reference":[{"key":"ref_1","first-page":"495","article-title":"Apoptosis: A review of programmed cell death","volume":"5","author":"Elmore","year":"2003","journal-title":"Toxicol Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.tcb.2008.08.001","article-title":"Apoptosis-induced compensatory proliferation. 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