{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T05:56:47Z","timestamp":1763359007802,"version":"3.45.0"},"reference-count":85,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research, India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006593","name":"Board of Research in Nuclear Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytoskeleton"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Polo\u2010like kinase 4 (PLK4) is a centrosome\u2010specific kinase aberrantly expressed in cancers. Drugs inhibiting its catalytic kinase domain are under clinical phase\u20101\/2 trials in patients with different leukemia types. However, the kinase domain of PLK4 shows structural similarity with other kinases. Therefore, drugs targeting the unique C\u2010terminal polo\u2010box domain (PBD) of PLK4 could provide better specificity. The knowledge of domain orientation in a full\u2010length PLK4 structure is imperative for drug discovery. In this work, we utilized ab\u00a0initio and threading approaches to predict the full\u2010length structure of human PLK4, which was employed for virtually screening the ChEMBL library. Among the hit compounds targeting the unique regions in PLK4, we identified Alectinib, which affects centrosome numbers corresponding to PLK4 levels at centrosomes. The FT\u2010IR analysis also confirmed Alectinib interaction with the PBD. Therefore, this work identifies a chemical scaffold that could be repurposed to target the unique regions of PLK4.<\/jats:p>","DOI":"10.1002\/cm.22020","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T10:14:15Z","timestamp":1742465655000},"page":"719-736","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Harnessing Structure Prediction of Polo\u2010Like Kinase 4 for Drug Repurposing"],"prefix":"10.1002","volume":"82","author":[{"given":"Harshita","family":"Kasera","sequence":"first","affiliation":[{"name":"Department of Bioscience &amp; Bioengineering Indian Institute of Technology Jodhpur  Jodhpur India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5928-6280","authenticated-orcid":false,"given":"Priyanka","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Bioscience &amp; Bioengineering Indian Institute of Technology Jodhpur  Jodhpur India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.07888"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201801014"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx246"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/bioengineering5040096"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1401"},{"issue":"1","key":"e_1_2_9_7_1","first-page":"94","article-title":"Alectinib and Brigatinib: New Second\u2010Generation ALK Inhibitors for the Treatment of Non\u2010Small Cell Lung Cancer","volume":"9","author":"Beardslee T.","year":"2018","journal-title":"Journal of the Advanced Practitioner in Oncology"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci700044s"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg558"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.150209"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560020916"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2010.484460"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2147\/tcrm.s3336"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2013.09.037"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11224\u2010022\u201002056\u20101"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0300577"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm216"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2022.100612"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.1c00203"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175723"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0092\u20108674(03)00725\u20106"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/11.6.681"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.068502"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00687"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1320"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt458"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200911102"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/pcmedi\/pbab001"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.34.15_suppl.e20598"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15143561"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(13)70465\u20100"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201003819\u20102"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211\u20105463.13913"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1101\/2023.11.06.565834"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1719760115"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1319656110"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1417967112"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201410105"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2007.07.002"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.12580"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024\u20103205(85)90337\u20106"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm400380m"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010018\u20101071\u20102"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.116115"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.14307"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041293"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7RA02518A"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541\u20107786.MCR\u201021\u20101010"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.05.006"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25051030"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/16.4.404"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2018.11.002"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.4084\/MJHID.2018.066"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.46054"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.898474"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2011.04.006"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1813310115"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6267"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.05.030"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/1759\u20107714.14357"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2846"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421\u2010021\u201000270\u20105"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b00741"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/ml500220a"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200808049"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.5"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2014.05.009"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033\u2010014\u20103546\u20102"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2012.08.025"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.129502"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22704"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20092112"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010009\u20100014\u20106"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1800260115"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202200490"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2014.971407"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202000565"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa5111"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3213"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28166172"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102105\u20109\u201040"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20264"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432\u2010019\u201002994\u20100"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010020\u201004098\u2010w"}],"container-title":["Cytoskeleton"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cm.22020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T04:42:40Z","timestamp":1763354560000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cm.22020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,20]]},"references-count":85,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/cm.22020"],"URL":"https:\/\/doi.org\/10.1002\/cm.22020","archive":["Portico"],"relation":{},"ISSN":["1949-3584","1949-3592"],"issn-type":[{"type":"print","value":"1949-3584"},{"type":"electronic","value":"1949-3592"}],"subject":[],"published":{"date-parts":[[2025,3,20]]},"assertion":[{"value":"2024-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}