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The CK2 inhibitor CX-4945 is in clinical trials for cancer treatment, but it has many off-target proteins. Therefore, the development of a bioavailable and specific CK2 inhibitor has been awaited. We previously discovered a specific CK2 inhibitor, GO289, from cell-based phenotypic screening of circadian clock modulators. However, the low water solubility and metabolic stability of GO289 have limited in vivo applications. Here, we developed GO289 derivatives with higher water solubility and metabolic stability. A derivative, GO847, changed the period length of cellular circadian rhythms similar to GO289 and inhibited the growth of acute myeloid leukemia (AML) cells. A proteomic profiling suggested the effects of GO847 and GO289 on pathways related to mitochondrial function, in addition to well-known CK2 targets: cell cycle, apoptosis, RNA metabolism, and protein synthesis. Consistent with this observation, both compounds impaired the metabolic flexibility of mitochondria in AML cells. After oral administration to mice, GO847 was detected in the plasma, liver, spleen, and bone marrow but not in the brain. Together, the findings show that GO847 is a promising candidate for targeting AML, a malignant blood cancer that requires effective treatment.<\/jats:p>","DOI":"10.1021\/prechem.5c00288","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T06:05:21Z","timestamp":1776233121000},"page":"1171-1179","source":"Crossref","is-referenced-by-count":0,"title":["An Orally Available\nDerivative of a Specific CK2 Inhibitor\nfor Regulating Circadian Rhythms and Acute Myeloid Leukemia"],"prefix":"10.1021","volume":"4","author":[{"given":"Tsuyoshi","family":"Oshima","sequence":"first","affiliation":[{"name":"Nagoya University , , Chikusa, ,","place":["Nagoya, Japan, 464-8601"]},{"name":"Nagoya University , , Chikusa, ,","place":["Nagoya, Japan, 464-8601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Setoyama","sequence":"additional","affiliation":[{"name":"Kyushu University Hospital Fukuoka , , ,","place":["Fukuoka, Japan, 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, , ,","place":["Gandhinagar, Gujarat, India, 382355"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mui","family":"Iida","sequence":"additional","affiliation":[{"name":"Nagoya University , , Chikusa, ,","place":["Nagoya, Japan, 464-8601"]},{"name":"Nagoya University , , Chikusa, ,","place":["Nagoya, Japan, 464-8601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhito","family":"Gotoh","sequence":"additional","affiliation":[{"name":"Tokai University School of Medicine , , , ,","place":["Isehara, Kanagawa, Japan, 259-1193"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangzhong","family":"Lin","sequence":"additional","affiliation":[{"name":"The University of Osaka , , , ,","place":["Suita, Osaka, Japan, 565-0871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikio","family":"Morita","sequence":"additional","affiliation":[{"name":"RaQualia Pharma Inc. , , Nakamura, ,","place":["Nagoya, Japan, 450-0003"]},{"name":"Nagoya University , , Chikusa, ,","place":["Nagoya, Japan, 464-8601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Ohmi","sequence":"additional","affiliation":[{"name":"RaQualia Pharma Inc. , , Nakamura, ,","place":["Nagoya, Japan, 450-0003"]},{"name":"Nagoya University , , Chikusa, ,","place":["Nagoya, Japan, 464-8601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Uchiumi","sequence":"additional","affiliation":[{"name":"Kyushu University Fukuoka , , ,","place":["Fukuoka, Japan, 812-8582"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumio","family":"Arai","sequence":"additional","affiliation":[{"name":"Kyushu University Fukuoka , , ,","place":["Fukuoka, Japan, 812-8582"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Haruta","sequence":"additional","affiliation":[{"name":"The University of Osaka , , , ,","place":["Suita, Osaka, Japan, 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812-8582"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5227-7894","authenticated-orcid":true,"given":"Kenichiro","family":"Itami","sequence":"additional","affiliation":[{"name":"Nagoya University , , Chikusa, ,","place":["Nagoya, Japan, 464-8601"]},{"name":"Nagoya University , , Chikusa, ,","place":["Nagoya, Japan, 464-8601"]},{"name":"RIKEN , , , ,","place":["Wako, Saitama, Japan, 351-0198"]},{"name":"RIKEN , , , ,","place":["Wako, Saitama, Japan, 351-0198"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4876-3608","authenticated-orcid":true,"given":"Tsuyoshi","family":"Hirota","sequence":"additional","affiliation":[{"name":"Nagoya University , , Chikusa, ,","place":["Nagoya, Japan, 464-8601"]},{"name":"Nagoya University , , Chikusa, ,","place":["Nagoya, Japan, 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Cancer"},{"key":"2026083104361363900_cit5","doi-asserted-by":"publisher","first-page":"2186","DOI":"10.1016\/j.chempr.2020.08.011","article-title":"Small Molecules Modulating\nMammalian Biological Clocks: Exciting\nNew Opportunities for Synthetic Chemistry","volume":"6","author":"Amaike","year":"2020","journal-title":"Chem-Us"},{"key":"2026083104361363900_cit6","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/s41573-020-00109-w","article-title":"Circadian\nrhythm as a therapeutic\ntarget","volume":"20","author":"Ruan","year":"2021","journal-title":"Nat. Rev. Drug Discov"},{"key":"2026083104361363900_cit7","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/j.chembiol.2023.08.014","article-title":"Metabolic\nand chemical architecture of the mammalian circadian clock","volume":"30","author":"Laothamatas","year":"2023","journal-title":"Cell Chem. Biol."},{"key":"2026083104361363900_cit8","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau9060","article-title":"Cell-based\nscreen identifies\na new potent and highly selective CK2 inhibitor for modulation of\ncircadian rhythms and cancer cell growth","volume":"5","author":"Oshima","year":"2019","journal-title":"Sci.\nAdv."},{"key":"2026083104361363900_cit9","first-page":"38","article-title":"Acute Myeloid Leukemia: A Review","volume":"103","author":"Pelcovits","year":"2020","journal-title":"R. I. Med. J."},{"key":"2026083104361363900_cit10","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.cell.2016.03.015","article-title":"Core Circadian Clock\nGenes Regulate Leukemia Stem Cells in AML","volume":"165","author":"Puram","year":"2016","journal-title":"Cell"},{"key":"2026083104361363900_cit11","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.ejmech.2019.03.063","article-title":"Synthetic\napproaches\nand pharmaceutical applications of chloro-containing molecules for\ndrug discovery: A critical review","volume":"173","author":"Fang","year":"2019","journal-title":"Eur. J. Med.\nChem."},{"key":"2026083104361363900_cit12","doi-asserted-by":"publisher","first-page":"3116","DOI":"10.2174\/092986711796391714","article-title":"Managing the liabilities arising from structural alerts:\na safe philosophy for medicinal chemists","volume":"18","author":"Edwards","year":"2011","journal-title":"Curr.\nMed. Chem."},{"key":"2026083104361363900_cit13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2022.116614","article-title":"Structural\nmodification aimed for improving solubility of lead compounds in early\nphase drug discovery","volume":"56","author":"Das","year":"2022","journal-title":"Bioorg. Med. Chem."},{"key":"2026083104361363900_cit14","doi-asserted-by":"publisher","first-page":"3071","DOI":"10.1021\/acs.orglett.5c00747","article-title":"Thioether Oxidation\nChemistry in\nReactive Oxygen Species (ROS)-Sensitive Trigger Design: A Kinetic\nAnalysis","volume":"27","author":"Abdelfattah","year":"2025","journal-title":"Org. Lett."},{"key":"2026083104361363900_cit15","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","article-title":"Genomic\nClassification and Prognosis\nin Acute Myeloid Leukemia","volume":"374","author":"Papaemmanuil","year":"2016","journal-title":"N Engl J. Med."},{"key":"2026083104361363900_cit16","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1042\/BJ20080309","article-title":"The selectivity\nof inhibitors of\nprotein kinase CK2: an update","volume":"415","author":"Pagano","year":"2008","journal-title":"Biochem. J."},{"key":"2026083104361363900_cit17","doi-asserted-by":"publisher","first-page":"10288","DOI":"10.1158\/0008-5472.CAN-10-1893","article-title":"CX-4945, an orally bioavailable selective inhibitor\nof protein kinase CK2, inhibits prosurvival and angiogenic signaling\nand exhibits antitumor efficacy","volume":"70","author":"Siddiqui-Jain","year":"2010","journal-title":"Cancer Res."},{"key":"2026083104361363900_cit18","doi-asserted-by":"publisher","first-page":"8478","DOI":"10.1021\/bi2008382","article-title":"Unprecedented selectivity and structural\ndeterminants of a new class of protein kinase CK2 inhibitors in clinical\ntrials for the treatment of cancer","volume":"50","author":"Battistutta","year":"2011","journal-title":"Biochemistry"},{"key":"2026083104361363900_cit19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094978","article-title":"Identification of a novel function\nof CX-4945 as a splicing regulator","volume":"9","author":"Kim","year":"2014","journal-title":"PLoS One"},{"key":"2026083104361363900_cit20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000559","article-title":"High-throughput\nchemical screen identifies a novel potent modulator of cellular circadian\nrhythms and reveals CKIalpha as a clock regulatory kinase","volume":"8","author":"Hirota","year":"2010","journal-title":"PLoS Biol."},{"key":"2026083104361363900_cit21","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1096\/fj.02-0473rev","article-title":"One-thousand-and-one substrates of\nprotein kinase CK2?","volume":"17","author":"Meggio","year":"2003","journal-title":"FASEB J."},{"key":"2026083104361363900_cit22","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.bbapap.2009.07.018","article-title":"Addiction to protein\nkinase CK2: a common denominator\nof diverse cancer cells?","volume":"1804","author":"Ruzzene","year":"2010","journal-title":"Biochim. Biophys.\nActa"},{"key":"2026083104361363900_cit23","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1016\/j.chembiol.2020.12.013","article-title":"Development of a potent and selective\nchemical probe for the pleiotropic kinase CK2","volume":"28","author":"Wells","year":"2021","journal-title":"Cell Chem. Biol."},{"key":"2026083104361363900_cit24","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.1021\/acs.jmedchem.2c01523","article-title":"Strategies of Targeting\nCK2 in Drug Discovery: Challenges, Opportunities,\nand Emerging Prospects","volume":"66","author":"Chen","year":"2023","journal-title":"J. Med. Chem."},{"key":"2026083104361363900_cit25","doi-asserted-by":"publisher","first-page":"20702","DOI":"10.1021\/acsomega.3c10478","article-title":"Recent\nAdvances in the Discovery\nof CK2 Inhibitors","volume":"9","author":"Al-Qadhi","year":"2024","journal-title":"ACS Omega"},{"key":"2026083104361363900_cit26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.117048","article-title":"Discovery of a novel,\nselective CK2 inhibitor class with an unusual\nbasic scaffold","volume":"282","author":"Khalifa","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"2026083104361363900_cit27","doi-asserted-by":"publisher","first-page":"12819","DOI":"10.1021\/acs.jmedchem.5c00695","article-title":"Discovery\nof KDX1381, a Bivalent CK2alpha Inhibitor for the Treatment of Solid\nTumors as a Single Agent or in Combination","volume":"68","author":"Marlhoux","year":"2025","journal-title":"J. Med. Chem."},{"key":"2026083104361363900_cit28","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1021\/jm101251q","article-title":"Discovery and SAR of 5-(3-chlorophenylamino)benzo[c][2,6]naphthyridine-8-carboxylic\nacid (CX-4945), the first clinical stage inhibitor of protein kinase\nCK2 for the treatment of cancer","volume":"54","author":"Pierre","year":"2011","journal-title":"J. Med. Chem."},{"key":"2026083104361363900_cit29","doi-asserted-by":"publisher","first-page":"21587","DOI":"10.1021\/acs.jmedchem.5c01807","article-title":"Exploiting the Cryptic\nalphaD Pocket of Casein Kinase\n2alpha (CK2alpha) to Deliver Highly Potent and Selective Type 1 Inhibitors","volume":"68","author":"Glossop","year":"2025","journal-title":"J. Med. Chem."},{"key":"2026083104361363900_cit30","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1007\/s13402-020-00566-w","article-title":"Role of CK2\ninhibitor\nCX-4945 in anti-cancer combination therapy - potential clinical relevance","volume":"43","author":"D\u2019Amore","year":"2020","journal-title":"Cell Oncol (Dordr)"}],"container-title":["Precision Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/prechem.5c00288","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/pcrhej\/article-pdf\/4\/8\/1171\/66264343\/prechem.5c00288.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/pcrhej\/article-pdf\/4\/8\/1171\/66264343\/prechem.5c00288.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T08:37:08Z","timestamp":1788165428000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/pcrhej\/article\/4\/8\/1171\/5233037\/An-Orally-Available-Derivative-of-a-Specific-CK2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":30,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4,15]]},"published-print":{"date-parts":[[2026,8,24]]}},"URL":"https:\/\/doi.org\/10.1021\/prechem.5c00288","relation":{},"ISSN":["2771-9316"],"issn-type":[{"value":"2771-9316","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]}}}