{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:50:35Z","timestamp":1786985435219,"version":"build-2736575974"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:00Z","timestamp":1714176000000},"content-version":"am","delay-in-days":362,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R15CA243109"],"award-info":[{"award-number":["1R15CA243109"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["SC2 GM130470"],"award-info":[{"award-number":["SC2 GM130470"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018306","name":"Museum of Natural Science, Louisiana State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018306","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic & Medicinal Chemistry Letters"],"published-print":{"date-parts":[[2023,5]]},"DOI":"10.1016\/j.bmcl.2023.129288","type":"journal-article","created":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T21:33:31Z","timestamp":1682199211000},"page":"129288","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["Identification of a novel spirocyclic Nek2 inhibitor using high throughput virtual screening"],"prefix":"10.1016","volume":"88","author":[{"given":"Ashif I.","family":"Bhuiyan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athena H.","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1089-084X","authenticated-orcid":false,"given":"Sarbani","family":"Ghoshal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugochi A.","family":"Adiele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dibyendu","family":"Dana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Yong","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6766-2530","authenticated-orcid":false,"given":"Karl R.","family":"Fath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanaji T.","family":"Talele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1799-9730","authenticated-orcid":false,"given":"Sanjai K.","family":"Pathak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmcl.2023.129288_b0005","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/35048096","article-title":"Mitotic kinases as regulators of cell division and its checkpoints","volume":"2","author":"Nigg","year":"2001","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.bmcl.2023.129288_b0010","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fcell.2018.00006","article-title":"Mechanisms of mitotic kinase regulation: a structural perspective","volume":"6","author":"Welburn","year":"2018","journal-title":"Front Cell Dev Biol"},{"key":"10.1016\/j.bmcl.2023.129288_b0015","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41576-019-0171-x","article-title":"Context is everything: aneuploidy in cancer","volume":"21","author":"Ben-David","year":"2020","journal-title":"Nat Rev Genet"},{"key":"10.1016\/j.bmcl.2023.129288_b0020","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/s41576-021-00411-2","article-title":"Aneuploidy in the driving seat","volume":"22","author":"Clyde","year":"2021","journal-title":"Nat Rev Genet"},{"key":"10.1016\/j.bmcl.2023.129288_b0025","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrc3995","article-title":"Centrosomes and cancer: revisiting a long-standing relationship","volume":"15","author":"Gonczy","year":"2015","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.bmcl.2023.129288_b0030","doi-asserted-by":"crossref","first-page":"102","DOI":"10.3389\/fcell.2017.00102","article-title":"Mitotic Regulation by NEK Kinase Networks","volume":"5","author":"Fry","year":"2017","journal-title":"Front Cell Dev Biol"},{"key":"10.1016\/j.bmcl.2023.129288_b0035","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.canlet.2004.12.028","article-title":"Centrosome amplification, chromosome instability and cancer development","volume":"230","author":"Fukasawa","year":"2005","journal-title":"Cancer Lett"},{"key":"10.1016\/j.bmcl.2023.129288_b0040","doi-asserted-by":"crossref","first-page":"9016","DOI":"10.1038\/s41598-021-88512-0","article-title":"The Nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells","volume":"11","author":"Rivera-Rivera","year":"2021","journal-title":"Sci Rep"},{"key":"10.1016\/j.bmcl.2023.129288_b0045","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.canlet.2005.06.017","article-title":"Nek2 kinase in chromosome instability and cancer","volume":"237","author":"Hayward","year":"2006","journal-title":"Cancer Lett"},{"key":"10.1016\/j.bmcl.2023.129288_b0050","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ccr.2012.12.001","article-title":"NEK2 induces drug resistance mainly through activation of efflux drug pumps and is associated with poor prognosis in myeloma and other cancers","volume":"23","author":"Zhou","year":"2013","journal-title":"Cancer Cell"},{"key":"10.1016\/j.bmcl.2023.129288_b0055","doi-asserted-by":"crossref","first-page":"11986","DOI":"10.18632\/oncotarget.2388","article-title":"NEK2 mediates ALDH1A1-dependent drug resistance in multiple myeloma","volume":"5","author":"Yang","year":"2014","journal-title":"Oncotarget"},{"key":"10.1016\/j.bmcl.2023.129288_b0060","first-page":"2364","article-title":"NEK2 promotes proliferation, migration and tumor growth of gastric cancer cells via regulating KDM5B\/H3K4me3","volume":"9","author":"Li","year":"2019","journal-title":"Am J Cancer Res"},{"key":"10.1016\/j.bmcl.2023.129288_b0065","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/273180","article-title":"Inhibition of Nek2 by small molecules affects proteasome activity","volume":"2014","author":"Meng","year":"2014","journal-title":"Biomed Res Int"},{"key":"10.1016\/j.bmcl.2023.129288_b0070","doi-asserted-by":"crossref","first-page":"e69","DOI":"10.1038\/oncsis.2013.34","article-title":"Centrosomal kinase Nek2 cooperates with oncogenic pathways to promote metastasis","volume":"2","author":"Das","year":"2013","journal-title":"Oncogenesis."},{"key":"10.1016\/j.bmcl.2023.129288_b0075","doi-asserted-by":"crossref","first-page":"843","DOI":"10.5604\/01.3001.0012.3146","article-title":"NEK2 promotes hepatoma metastasis and serves as biomarker for high recurrence risk after hepatic resection","volume":"17","author":"Chang","year":"2018","journal-title":"Ann Hepatol"},{"key":"10.1016\/j.bmcl.2023.129288_b0080","doi-asserted-by":"crossref","first-page":"5574","DOI":"10.1002\/cam4.2474","article-title":"Are 90% of deaths from cancer caused by metastases?","volume":"8","author":"Dillekas","year":"2019","journal-title":"Cancer Med"},{"key":"10.1016\/j.bmcl.2023.129288_b0085","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1126\/science.1203543","article-title":"A perspective on cancer cell metastasis","volume":"331","author":"Chaffer","year":"2011","journal-title":"Science"},{"key":"10.1016\/j.bmcl.2023.129288_b0090","doi-asserted-by":"crossref","first-page":"7370","DOI":"10.1158\/0008-5472.CAN-04-0960","article-title":"The centrosomal kinase Nek2 displays elevated levels of protein expression in human breast cancer","volume":"64","author":"Hayward","year":"2004","journal-title":"Cancer Res"},{"key":"10.1016\/j.bmcl.2023.129288_b0095","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s11060-017-2401-4","article-title":"Overexpression of NIMA-related kinase 2 is associated with poor prognoses in malignant glioma","volume":"132","author":"Liu","year":"2017","journal-title":"J Neurooncol"},{"key":"10.1016\/j.bmcl.2023.129288_b0100","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/ajh.21549","article-title":"Identification of molecular targets associated with transformed diffuse large B cell lymphoma using highly purified tumor cells","volume":"84","author":"Andreasson","year":"2009","journal-title":"Am J Hematol"},{"key":"10.1016\/j.bmcl.2023.129288_b0105","doi-asserted-by":"crossref","first-page":"5103","DOI":"10.1038\/onc.2010.253","article-title":"The Ras oncogene signals centrosome amplification in mammary epithelial cells through cyclin D1\/Cdk4 and Nek2","volume":"29","author":"Zeng","year":"2010","journal-title":"Oncogene"},{"key":"10.1016\/j.bmcl.2023.129288_b0110","doi-asserted-by":"crossref","first-page":"745","DOI":"10.3892\/or.2013.2910","article-title":"Upregulation of NEK2 is associated with drug resistance in ovarian cancer","volume":"31","author":"Liu","year":"2014","journal-title":"Oncol Rep"},{"key":"10.1016\/j.bmcl.2023.129288_b0115","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1080\/15384101.2016.1152430","article-title":"Targeting NEK2 as a promising therapeutic approach for cancer treatment","volume":"15","author":"Fang","year":"2016","journal-title":"Cell Cycle"},{"key":"10.1016\/j.bmcl.2023.129288_b0120","doi-asserted-by":"crossref","first-page":"839","DOI":"10.3892\/ijo.2013.1788","article-title":"Nek2-targeted ASO or siRNA pretreatment enhances anticancer drug sensitivity in triplenegative breast cancer cells","volume":"42","author":"Lee","year":"2013","journal-title":"Int J Oncol"},{"key":"10.1016\/j.bmcl.2023.129288_b0125","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/j.1349-7006.2008.01007.x","article-title":"Nek2 as a novel molecular target for the treatment of breast carcinoma","volume":"100","author":"Tsunoda","year":"2009","journal-title":"Cancer Sci"},{"key":"10.1016\/j.bmcl.2023.129288_b0130","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1111\/j.1349-7006.2010.01504.x","article-title":"Novel combination treatment for colorectal cancer using Nek2 siRNA and cisplatin","volume":"101","author":"Suzuki","year":"2010","journal-title":"Cancer Sci"},{"key":"10.1016\/j.bmcl.2023.129288_b0135","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1177\/1087057110376537","article-title":"Identification by high-throughput screening of viridin analogs as biochemical and cell-based inhibitors of the cell cycle-regulated nek2 kinase","volume":"15","author":"Hayward","year":"2010","journal-title":"J Biomol Screen"},{"key":"10.1016\/j.bmcl.2023.129288_b0140","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112118","article-title":"Discovery of T-1101 tosylate as a first-in-class clinical candidate for Hec1\/Nek2 inhibition in cancer therapy","volume":"191","author":"Chuang","year":"2020","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.bmcl.2023.129288_b0145","doi-asserted-by":"crossref","first-page":"7682","DOI":"10.1021\/jm1008727","article-title":"Aminopyrazine inhibitors binding to an unusual inactive conformation of the mitotic kinase Nek2: SAR and structural characterization","volume":"53","author":"Whelligan","year":"2010","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2023.129288_b0150","doi-asserted-by":"crossref","first-page":"3228","DOI":"10.1021\/jm201683b","article-title":"Design of potent and selective hybrid inhibitors of the mitotic kinase Nek2: structure-activity relationship, structural biology, and cellular activity","volume":"55","author":"Innocenti","year":"2012","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2023.129288_b0155","doi-asserted-by":"crossref","first-page":"6833","DOI":"10.1074\/jbc.M609721200","article-title":"Structure and regulation of the human Nek2 centrosomal kinase","volume":"282","author":"Rellos","year":"2007","journal-title":"J Biol Chem"},{"key":"10.1016\/j.bmcl.2023.129288_b0160","doi-asserted-by":"crossref","first-page":"4398","DOI":"10.1016\/j.bmcl.2013.05.072","article-title":"Identification of potent Yes1 kinase inhibitors using a library screening approach","volume":"23","author":"Patel","year":"2013","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmcl.2023.129288_b0165","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.chembiol.2011.04.013","article-title":"A general framework for inhibitor resistance in protein kinases","volume":"18","author":"Balzano","year":"2011","journal-title":"Chem Biol"},{"key":"10.1016\/j.bmcl.2023.129288_b0170","doi-asserted-by":"crossref","first-page":"4133","DOI":"10.1021\/jm200222m","article-title":"Irreversible Nek2 kinase inhibitors with cellular activity","volume":"54","author":"Henise","year":"2011","journal-title":"J Med Chem"},{"issue":"Pt 19","key":"10.1016\/j.bmcl.2023.129288_b0175","first-page":"4423","article-title":"Cell cycle regulation by the NEK family of protein kinases","volume":"125","author":"Fry","year":"2012","journal-title":"J Cell Sci"},{"key":"10.1016\/j.bmcl.2023.129288_b0180","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1146\/annurev-biochem-090308-173656","article-title":"The evolution of protein kinase inhibitors from antagonists to agonists of cellular signaling","volume":"80","author":"Dar","year":"2011","journal-title":"Annu Rev Biochem"},{"key":"10.1016\/j.bmcl.2023.129288_b0185","doi-asserted-by":"crossref","first-page":"6541","DOI":"10.1002\/j.1460-2075.1996.tb01045.x","article-title":"Mechanism of activation of protein kinase B by insulin and IGF-1","volume":"15","author":"Alessi","year":"1996","journal-title":"EMBO J"},{"key":"10.1016\/j.bmcl.2023.129288_b0190","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3389\/fcell.2019.00107","article-title":"In vitro cell migration, invasion, and adhesion assays: from cell imaging to data analysis","volume":"7","author":"Pijuan","year":"2019","journal-title":"Front Cell Dev Biol"},{"key":"10.1016\/j.bmcl.2023.129288_b0195","first-page":"1023","article-title":"NEK2 promotes hepatocellular carcinoma migration and invasion through modulation of the epithelial-mesenchymal transition","volume":"39","author":"Zhang","year":"2018","journal-title":"Oncol Rep"},{"key":"10.1016\/j.bmcl.2023.129288_b0200","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3892\/ijo.2017.3837","article-title":"NEK2 serves as a prognostic biomarker for hepatocellular carcinoma","volume":"50","author":"Li","year":"2017","journal-title":"Int J Oncol"},{"key":"10.1016\/j.bmcl.2023.129288_b0205","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1021\/jm1011726","article-title":"Benzimidazole inhibitors induce a DFG-out conformation of never in mitosis gene A-related kinase 2 (Nek2) without binding to the back pocket and reveal a nonlinear structure-activity relationship","volume":"54","author":"Solanki","year":"2011","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2023.129288_b0210","doi-asserted-by":"crossref","first-page":"79327","DOI":"10.18632\/oncotarget.12687","article-title":"Preclinical activity of MBM-5 in gastrointestinal cancer by inhibiting NEK2 kinase activity","volume":"7","author":"Fang","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.bmcl.2023.129288_b0215","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1172\/JCI89092","article-title":"Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2","volume":"127","author":"Wang","year":"2017","journal-title":"J Clin Investig"},{"key":"10.1016\/j.bmcl.2023.129288_b0220","doi-asserted-by":"crossref","first-page":"19089","DOI":"10.18632\/oncotarget.13249","article-title":"Structure-guided design of purine-based probes for selective Nek2 inhibition","volume":"8","author":"Coxon","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.bmcl.2023.129288_b0225","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1039\/D0MD00074D","article-title":"2-Arylamino-6-ethynylpurines are cysteine-targeting irreversible inhibitors of Nek2 kinase","volume":"11","author":"Matheson","year":"2020","journal-title":"RSC Med Chem."}],"container-title":["Bioorganic & Medicinal Chemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X2300166X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X2300166X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:21:55Z","timestamp":1778570515000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960894X2300166X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5]]},"references-count":45,"alternative-id":["S0960894X2300166X"],"URL":"https:\/\/doi.org\/10.1016\/j.bmcl.2023.129288","relation":{},"ISSN":["0960-894X"],"issn-type":[{"value":"0960-894X","type":"print"}],"subject":[],"published":{"date-parts":[[2023,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Identification of a novel spirocyclic Nek2 inhibitor using high throughput virtual screening","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmcl.2023.129288","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"129288"}}