{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:51:12Z","timestamp":1790351472910,"version":"4.1.0"},"reference-count":24,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bristol-Myers-Squibb","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017517","name":"Ohara Pharmaceuticals","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100017517","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients with chronic myeloid leukemia (CML) respond to tyrosine kinase inhibitors (TKIs); however, CML leukemic stem cells (LSCs) exhibit BCR::ABL kinase-independent growth and are insensitive to TKIs, leading to disease relapse. To prevent this, new therapies targeting CML-LSCs are needed. Rates of mitochondria-mediated oxidative phosphorylation (OXPHOS) in CD34+CML cells within the primitive CML cell population are higher than those in normal undifferentiated hematopoietic cells; therefore, the inhibition of OXPHOS in CML-LSCs may be a potential cure for CML. NK-128 (C33H61NO5S) is a structurally simplified analog of JCI-20679, the design of which was based on annonaceous acetogenins. NK-128 exhibits antitumor activity against glioblastoma and human colon cancer cells by inhibiting OXPHOS and activating AMP-activated protein kinase (AMPK). Here, we demonstrate that NK-128 effectively suppresses the growth of CML cell lines and that the combination of imatinib and NK-128 is more potent than either alone in a CML xenograft mouse model. We also found that NK-128 inhibits colony formation by CD34+ CML cells isolated from the bone marrow of untreated CML patients. Taken together, these findings suggest that targeting OXPHOS is a beneficial approach to eliminating CML-LSCs, and may improve the treatment of CML.<\/jats:p>","DOI":"10.3390\/ijms252011093","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T09:14:48Z","timestamp":1729242888000},"page":"11093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting Oxidative Phosphorylation with a Novel Thiophene Carboxamide Increases the Efficacy of Imatinib against Leukemic Stem Cells in Chronic Myeloid Leukemia"],"prefix":"10.3390","volume":"25","author":[{"given":"Kana","family":"Kusaba","sequence":"first","affiliation":[{"name":"Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, Faculty of Medicine, Saga University, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Kidoguchi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan"},{"name":"Department of Drug Discovery and Biomedical Sciences, Faculty of Medicine, Saga University, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, Faculty of Medicine, Saga University, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Tomoda","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, Faculty of Medicine, Saga University, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimi","family":"Hoshiko","sequence":"additional","affiliation":[{"name":"Clinical Research Center, Saga Medical School Hospital, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4544-4583","authenticated-orcid":false,"given":"Naoto","family":"Kojima","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Nakata","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Oncology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Kimura","sequence":"additional","affiliation":[{"name":"Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan"},{"name":"Department of Drug Discovery and Biomedical Sciences, Faculty of Medicine, Saga University, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3138","DOI":"10.1182\/blood.2021011722","article-title":"How I treat chronic-phase chronic myelogenous leukemia","volume":"139","author":"Berman","year":"2022","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chen, Y., Zou, J., Cheng, F., and Li, W. 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