{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T18:51:15Z","timestamp":1780685475600,"version":"3.54.1"},"reference-count":32,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"am","delay-in-days":300,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009917","name":"U.S. Naval Research Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["1-DA1101"],"award-info":[{"award-number":["1-DA1101"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic & Medicinal Chemistry"],"published-print":{"date-parts":[[2022,9]]},"DOI":"10.1016\/j.bmc.2022.116890","type":"journal-article","created":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T12:19:31Z","timestamp":1655727571000},"page":"116890","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Improving the solubility and antileukemia activity of Wnt\/\u03b2-catenin signaling inhibitors by disrupting molecular planarity"],"prefix":"10.1016","volume":"69","author":[{"given":"Yong","family":"Ai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srilatha","family":"Sakamuru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Imler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghang","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengtian","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmc.2022.116890_b0005","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1002\/jcp.1041210421","article-title":"The human c-abl oncogene in the Philadelphia translocation","volume":"3","author":"Groffen","year":"1984","journal-title":"J Cell Physiol Suppl."},{"key":"10.1016\/j.bmc.2022.116890_b0010","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nrclinonc.2016.139","article-title":"Tyrosine kinase inhibitors in chronic myeloid leukaemia: which, when, for whom?","volume":"14","author":"Rosti","year":"2017","journal-title":"Nat Rev Clin Oncol."},{"key":"10.1016\/j.bmc.2022.116890_b0015","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1182\/blood.V99.1.319","article-title":"Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro","volume":"99","author":"Graham","year":"2002","journal-title":"Blood"},{"key":"10.1016\/j.bmc.2022.116890_b0020","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/nrc1567","article-title":"Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia","volume":"5","author":"Ren","year":"2005","journal-title":"Nat Rev Cancer."},{"key":"10.1016\/j.bmc.2022.116890_b0025","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1056\/NEJMoa040258","article-title":"Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML","volume":"351","author":"Jamieson","year":"2004","journal-title":"N Engl J Med."},{"key":"10.1016\/j.bmc.2022.116890_b0030","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0092-8674(00)81333-1","article-title":"Lessons from hereditary colorectal cancer","volume":"87","author":"Kinzler","year":"1996","journal-title":"Cell"},{"key":"10.1016\/j.bmc.2022.116890_b0035","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.cell.2012.05.012","article-title":"Wnt\/beta-catenin signaling and disease","volume":"149","author":"Clevers","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.bmc.2022.116890_b0040","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1086\/382196","article-title":"Homozygous WNT3 mutation causes tetra-amelia in a large consanguineous family","volume":"74","author":"Niemann","year":"2004","journal-title":"Am J Hum Genet."},{"key":"10.1016\/j.bmc.2022.116890_b0045","doi-asserted-by":"crossref","first-page":"29577","DOI":"10.1074\/jbc.M203570200","article-title":"The polycystic kidney disease-1 promoter is a target of the beta-catenin\/T-cell factor pathway","volume":"277","author":"Rodova","year":"2002","journal-title":"J Biol Chem."},{"key":"10.1016\/j.bmc.2022.116890_b0050","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1111\/exd.12255","article-title":"Canonical Wnt signalling as a key regulator of fibrogenesis - implications for targeted therapies?","volume":"22","author":"Dees","year":"2013","journal-title":"Exp Dermatol."},{"key":"10.1016\/j.bmc.2022.116890_b0055","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/S0002-9440(10)64282-4","article-title":"Aberrant Wnt\/beta-catenin pathway activation in idiopathic pulmonary fibrosis","volume":"162","author":"Chilosi","year":"2003","journal-title":"Am J Pathol."},{"key":"10.1016\/j.bmc.2022.116890_b0060","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0920-9964(98)00179-0","article-title":"Increased expression of Wnt-1 in schizophrenic brains","volume":"38","author":"Miyaoka","year":"1999","journal-title":"Schizophr Res."},{"key":"10.1016\/j.bmc.2022.116890_b0065","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.neulet.2003.09.017","article-title":"The human frizzled-3 (FZD3) gene on chromosome 8p21, a receptor gene for Wnt ligands, is associated with the susceptibility to schizophrenia","volume":"353","author":"Katsu","year":"2003","journal-title":"Neurosci Lett."},{"key":"10.1016\/j.bmc.2022.116890_b0070","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0924-977X(01)00131-6","article-title":"GSK-3 and the neurodevelopmental hypothesis of schizophrenia","volume":"12","author":"Kozlovsky","year":"2002","journal-title":"Eur Neuropsychopharmacol."},{"key":"10.1016\/j.bmc.2022.116890_b0075","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S0166-2236(00)02031-2","article-title":"Alzheimer's disease-do tauists and baptists finally shake hands?","volume":"25","author":"Mudher","year":"2002","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.bmc.2022.116890_b0080","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0165-6147(03)00100-7","article-title":"The Wnt pathway, cell-cycle activation and beta-amyloid: novel therapeutic strategies in Alzheimer's disease?","volume":"24","author":"Caricasole","year":"2003","journal-title":"Trends Pharmacol Sci."},{"key":"10.1016\/j.bmc.2022.116890_b0085","doi-asserted-by":"crossref","unstructured":"Oh DY, Olefsky JM, Medicine. Wnt fans the flames in obesity. Science. 2010;329: 397-398. 10.1126\/science.1193404.","DOI":"10.1126\/science.1193404"},{"key":"10.1016\/j.bmc.2022.116890_b0090","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/S0083-6729(08)00619-5","article-title":"Role of Wnt signaling in the development of type 2 diabetes","volume":"80","author":"Bordonaro","year":"2009","journal-title":"Vitam Horm."},{"key":"10.1016\/j.bmc.2022.116890_b0095","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1055\/s-0028-1119408","article-title":"Wnt-signalling and the metabolic syndrome","volume":"41","author":"Schinner","year":"2009","journal-title":"Horm Metab Res."},{"key":"10.1016\/j.bmc.2022.116890_b0100","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0959-437X(02)00013-8","article-title":"Tumor suppression by Ink4a-Arf: progress and puzzles","volume":"13","author":"Lowe","year":"2003","journal-title":"Curr Opin Genet Dev."},{"key":"10.1016\/j.bmc.2022.116890_b0105","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1073\/pnas.0510423103","article-title":"Gene expression changes associated with progression and response in chronic myeloid leukemia","volume":"103","author":"Radich","year":"2006","journal-title":"Proc Natl Acad Sci U S A."},{"key":"10.1016\/j.bmc.2022.116890_b0110","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/35102167","article-title":"Stem cells, cancer, and cancer stem cells","volume":"414","author":"Reya","year":"2001","journal-title":"Nature"},{"key":"10.1016\/j.bmc.2022.116890_b0115","doi-asserted-by":"crossref","unstructured":"Xiang W, Cheong JK, Ang SH, Teo B, Xu P, Asari K, Sun WT, Than H, Bunte RM, Virshup DM, Chuah C. Pyrvinium selectively targets blast phase-chronic myeloid leukemia through inhibition of mitochondrial respiration. Oncotarget. 2015;6:33769\u201333780. 10.18632\/oncotarget.5615.","DOI":"10.18632\/oncotarget.5615"},{"key":"10.1016\/j.bmc.2022.116890_b0120","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1021\/acs.jmedchem.8b01408","article-title":"Triazole-based inhibitors of the wnt\/beta-catenin signaling pathway improve glucose and lipid metabolisms in diet-induced obese mice","volume":"62","author":"Obianom","year":"2019","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmc.2022.116890_b0125","doi-asserted-by":"crossref","first-page":"11151","DOI":"10.1021\/acs.jmedchem.9b01252","article-title":"Pyrazole-4-carboxamide (YW2065): a therapeutic candidate for colorectal cancer via dual activities of wnt\/beta-catenin signaling inhibition and AMP-activated protein kinase (AMPK) activation","volume":"62","author":"Yang","year":"2019","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmc.2022.116890_b0130","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1021\/jm101356p","article-title":"Improvement in aqueous solubility in small molecule drug discovery programs by disruption of molecular planarity and symmetry","volume":"54","author":"Ishikawa","year":"2011","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmc.2022.116890_b0135","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1021\/jm801586s","article-title":"Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily","volume":"52","author":"Schroeder","year":"2009","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmc.2022.116890_b0140","doi-asserted-by":"crossref","first-page":"6672","DOI":"10.1021\/jm0605233","article-title":"Matched molecular pairs as a guide in the optimization of pharmaceutical properties; a study of aqueous solubility, plasma protein binding and oral exposure","volume":"49","author":"Leach","year":"2006","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmc.2022.116890_b0145","doi-asserted-by":"crossref","first-page":"5365","DOI":"10.1021\/acs.jmedchem.0c02036","article-title":"Modulation of the passive permeability of semipeptidic macrocycles: N- and C-methylations fine-tune conformation and properties","volume":"64","author":"Comeau","year":"2021","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmc.2022.116890_b0150","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1038\/nchembio.2203","article-title":"Structural and conformational determinants of macrocycle cell permeability","volume":"12","author":"Over","year":"2016","journal-title":"Nat Chem Biol."},{"key":"10.1016\/j.bmc.2022.116890_b0155","doi-asserted-by":"crossref","first-page":"7409","DOI":"10.1021\/acs.jmedchem.5b00919","article-title":"Going out on a limb: delineating the effects of beta-branching, N-methylation, and side chain size on the passive permeability, solubility, and flexibility of sanguinamide A analogues","volume":"58","author":"Bockus","year":"2015","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmc.2022.116890_b0160","doi-asserted-by":"crossref","first-page":"6774","DOI":"10.1021\/acs.jmedchem.0c00013","article-title":"Structure-permeability relationship of semipeptidic macrocycles-understanding and optimizing passive permeability and efflux ratio","volume":"63","author":"Le Roux","year":"2020","journal-title":"J Med Chem."}],"container-title":["Bioorganic & Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089622002826?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089622002826?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T01:20:25Z","timestamp":1760836825000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0968089622002826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9]]},"references-count":32,"alternative-id":["S0968089622002826"],"URL":"https:\/\/doi.org\/10.1016\/j.bmc.2022.116890","relation":{},"ISSN":["0968-0896"],"issn-type":[{"value":"0968-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2022,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Improving the solubility and antileukemia activity of Wnt\/\u03b2-catenin signaling inhibitors by disrupting molecular planarity","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmc.2022.116890","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"116890"}}