{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:44:01Z","timestamp":1788536641319,"version":"build-2803163510"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:00:00Z","timestamp":1730160000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:00:00Z","timestamp":1730160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Divers"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1007\/s11030-024-11022-4","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T05:11:08Z","timestamp":1730178668000},"page":"4117-4129","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Repurposed pharmacotherapy: targeting cathepsin L with repurposed drugs in virtual screening"],"prefix":"10.1007","volume":"29","author":[{"given":"Mohammad","family":"Khalid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed H.","family":"Alqarni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed I.","family":"Foudah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,29]]},"reference":[{"key":"11022_CR1","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1002\/ijc.33232","volume":"148","author":"S Pilleron","year":"2021","unstructured":"Pilleron S, Soto-Perez-de-Celis E, Vignat J, Ferlay J, Soerjomataram I, Bray F, Sarfati D (2021) Estimated global cancer incidence in the oldest adults in 2018 and projections to 2050. Int J Cancer 148:601\u2013608. https:\/\/doi.org\/10.1002\/ijc.33232","journal-title":"Int J Cancer"},{"key":"11022_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2024.167120","volume":"1870","author":"S Chakraborty","year":"2024","unstructured":"Chakraborty S, Sharma G, Karmakar S, Banerjee S (2024) Multi-OMICS approaches in cancer biology: New era in cancer therapy. Biochim Biophys Acta Mol Basis Dis 1870:167120. https:\/\/doi.org\/10.1016\/j.bbadis.2024.167120","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"11022_CR3","doi-asserted-by":"publisher","first-page":"S11285","DOI":"10.4137\/cgm.s11285","volume":"7","author":"HA Goubran","year":"2014","unstructured":"Goubran HA, Kotb RR, Stakiw J, Emara ME, Burnouf T (2014) Regulation of tumor growth and metastasis: the role of tumor microenvironment. Cancer Growth Metastasis 7:S11285. https:\/\/doi.org\/10.4137\/cgm.s11285","journal-title":"Cancer Growth Metastasis"},{"key":"11022_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2018.07.010","author":"A Pi\u0161lar","year":"2018","unstructured":"Pi\u0161lar A, Jewett A, Kos J (2018) Cysteine cathepsins: their biological and molecular significance in cancer stem cells. Semin Cancer Biol. https:\/\/doi.org\/10.1016\/j.semcancer.2018.07.010","journal-title":"Semin Cancer Biol"},{"key":"11022_CR5","first-page":"3357","volume":"26","author":"I Zajc","year":"2006","unstructured":"Zajc I, Hreljac I, Lah T (2006) Cathepsin L affects apoptosis of glioblastoma cells: a potential implication in the design of cancer therapeutics. Anticancer Res 26:3357\u20133364","journal-title":"Anticancer Res"},{"key":"11022_CR6","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1007\/s12094-015-1424-6","volume":"18","author":"F Cui","year":"2016","unstructured":"Cui F, Wang W, Wu D, He X, Wu J, Wang M (2016) Overexpression of Cathepsin L is associated with gefitinib resistance in non-small cell lung cancer. Clin Transl Oncol 18:722\u2013727. https:\/\/doi.org\/10.1007\/s12094-015-1424-6","journal-title":"Clin Transl Oncol"},{"key":"11022_CR7","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.3892\/or.2014.2967","volume":"31","author":"W Zhang","year":"2014","unstructured":"Zhang W, Wang S, Wang Q, Yang Z, Pan Z, Li L (2014) Overexpression of cysteine cathepsin L is a marker of invasion and metastasis in ovarian cancer. Oncol Rep 31:1334\u20131342. https:\/\/doi.org\/10.3892\/or.2014.2967","journal-title":"Oncol Rep"},{"key":"11022_CR8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3390\/osteology1010002","volume":"1","author":"HO Fasanya","year":"2020","unstructured":"Fasanya HO, Siemann DW (2020) The role of cathepsins in the growth of primary and secondary neoplasia in the bone. Osteology 1:3\u201328. https:\/\/doi.org\/10.3390\/osteology1010002","journal-title":"Osteology"},{"key":"11022_CR9","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.pharmthera.2015.08.007","volume":"155","author":"DR Sudhan","year":"2015","unstructured":"Sudhan DR, Siemann DW (2015) Cathepsin L targeting in cancer treatment. Pharmacol Ther 155:105\u2013116. https:\/\/doi.org\/10.1016\/j.pharmthera.2015.08.007","journal-title":"Pharmacol Ther"},{"key":"11022_CR10","doi-asserted-by":"publisher","first-page":"698","DOI":"10.3390\/molecules25030698","volume":"25","author":"D Dana","year":"2020","unstructured":"Dana D, Pathak SK (2020) A review of small molecule inhibitors and functional probes of human cathepsin L. Molecules 25:698. https:\/\/doi.org\/10.3390\/molecules25030698","journal-title":"Molecules"},{"key":"11022_CR11","doi-asserted-by":"publisher","first-page":"939","DOI":"10.4155\/fmc-2019-0307","volume":"12","author":"N Berdigaliyev","year":"2020","unstructured":"Berdigaliyev N, Aljofan M (2020) An overview of drug discovery and development. Future Med Chem 12:939\u2013947. https:\/\/doi.org\/10.4155\/fmc-2019-0307","journal-title":"Future Med Chem"},{"key":"11022_CR12","doi-asserted-by":"publisher","first-page":"59","DOI":"10.12793\/tcp.2019.27.2.59","volume":"27","author":"K Park","year":"2019","unstructured":"Park K (2019) A review of computational drug repurposing. Transl Clin Pharmacol 27:59\u201363. https:\/\/doi.org\/10.12793\/tcp.2019.27.2.59","journal-title":"Transl Clin Pharmacol"},{"key":"11022_CR13","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nrd.2018.168","volume":"18","author":"S Pushpakom","year":"2019","unstructured":"Pushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A, Doig A, Guilliams T, Latimer J, McNamee C (2019) Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov 18:41\u201358. https:\/\/doi.org\/10.1038\/nrd.2018.168","journal-title":"Nat Rev Drug Discov"},{"key":"11022_CR14","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.1016\/j.drudis.2019.06.014","volume":"24","author":"V Parvathaneni","year":"2019","unstructured":"Parvathaneni V, Kulkarni NS, Muth A, Gupta V (2019) Drug repurposing: a promising tool to accelerate the drug discovery process. Drug Discov Today 24:2076\u20132085. https:\/\/doi.org\/10.1016\/j.drudis.2019.06.014","journal-title":"Drug Discov Today"},{"key":"11022_CR15","doi-asserted-by":"publisher","first-page":"351","DOI":"10.2174\/1574893615999200703113200","volume":"16","author":"B Shaker","year":"2021","unstructured":"Shaker B, Tran KM, Jung C, Na D (2021) Introduction of advanced methods for structure-based drug discovery. Curr Bioinform 16:351\u2013363. https:\/\/doi.org\/10.2174\/1574893615999200703113200","journal-title":"Curr Bioinform"},{"key":"11022_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-822312-3.00017-5","author":"A Sellami","year":"2021","unstructured":"Sellami A, R\u00e9au M, Langenfeld F, Lagarde N, Montes M (2021) Virtual libraries for docking methods: guidelines for the selection and the preparation. Mol Dock Comput-Aided Drug Des. https:\/\/doi.org\/10.1016\/B978-0-12-822312-3.00017-5","journal-title":"Mol Dock Comput-Aided Drug Des"},{"key":"11022_CR17","doi-asserted-by":"publisher","first-page":"11231","DOI":"10.1080\/07391102.2022.2160818","volume":"41","author":"S Khan","year":"2023","unstructured":"Khan S, Punnoose K, Bishara NZA, Ali R, Khan S, Ahmad S, Marouf HA-A, Mirza S, Ishrat R, Haque S (2023) Identification of potential inhibitor molecule against MabA protein of Mycobacterium leprae by integrated in silico approach. J Biomol Struct Dyn 41:11231\u201311246. https:\/\/doi.org\/10.1080\/07391102.2022.2160818","journal-title":"J Biomol Struct Dyn"},{"key":"11022_CR18","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s10822-016-0005-2","volume":"31","author":"K Liu","year":"2017","unstructured":"Liu K, Watanabe E, Kokubo H (2017) Exploring the stability of ligand binding modes to proteins by molecular dynamics simulations. J Comput-aided Mol Des 31:201\u2013211. https:\/\/doi.org\/10.1007\/s10822-016-0005-2","journal-title":"J Comput-aided Mol Des"},{"key":"11022_CR19","doi-asserted-by":"publisher","first-page":"D1265","DOI":"10.1093\/nar\/gkad976","volume":"52","author":"C Knox","year":"2024","unstructured":"Knox C, Wilson M, Klinger CM, Franklin M, Oler E, Wilson A, Pon A, Cox J, Chin NE, Strawbridge SA (2024) DrugBank 6.0: the DrugBank Knowledgebase for 2024. Nucleic Acids Res 52:D1265\u2013D1275. https:\/\/doi.org\/10.1093\/nar\/gkad976","journal-title":"Nucleic Acids Res"},{"key":"11022_CR20","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455\u2013461. https:\/\/doi.org\/10.1002\/jcc.21334","journal-title":"J Comput Chem"},{"key":"11022_CR21","unstructured":"DeLano WL (2002) Pymol: An open-source molecular graphics tool. CCP4 Newsl Protein Crystallogr 40:82\u201392."},{"key":"11022_CR22","unstructured":"Visualizer D (2005) Discovery Studio Visualizer. 2. Accelrys Software Inc."},{"key":"11022_CR23","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.2174\/1568026618666181025114157","volume":"18","author":"AA Naqvi","year":"2018","unstructured":"Naqvi AA, Mohammad T, Hasan GM, Hassan MI (2018) Advancements in docking and molecular dynamics simulations towards ligand-receptor interactions and structure-function relationships. Curr Top Med Chem 18:1755\u20131768. https:\/\/doi.org\/10.2174\/1568026618666181025114157","journal-title":"Curr Top Med Chem"},{"key":"11022_CR24","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1002\/anie.201006781","volume":"50","author":"LA Hardegger","year":"2011","unstructured":"Hardegger LA, Kuhn B, Spinnler B, Anselm L, Ecabert R, Stihle M, Gsell B, Thoma R, Diez J, Benz J (2011) Systematic investigation of halogen bonding in protein\u2013ligand interactions. Angew Chem Int Ed 50:314\u2013318. https:\/\/doi.org\/10.1002\/anie.201006781","journal-title":"Angew Chem Int Ed"},{"key":"11022_CR25","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1007\/s10593-014-1496-1","volume":"50","author":"D Filimonov","year":"2014","unstructured":"Filimonov D, Lagunin A, Gloriozova T, Rudik A, Druzhilovskii D, Pogodin P, Poroikov V (2014) Prediction of the biological activity spectra of organic compounds using the PASS online web resource. Chem Heterocycl Compd 50:444\u2013457. https:\/\/doi.org\/10.1007\/s10593-014-1496-1","journal-title":"Chem Heterocycl Compd"},{"key":"11022_CR26","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-15-6815-2_7","author":"R Shukla","year":"2020","unstructured":"Shukla R, Tripathi T (2020) Molecular dynamics simulation of protein and protein\u2013ligand complexes. Comput Aided Drug Des. https:\/\/doi.org\/10.1007\/978-981-15-6815-2_7","journal-title":"Comput Aided Drug Des"},{"key":"11022_CR27","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1002\/jcc.1078","volume":"22","author":"LD Schuler","year":"2001","unstructured":"Schuler LD, Daura X, Van Gunsteren WF (2001) An improved GROMOS96 force field for aliphatic hydrocarbons in the condensed phase. J Comput Chem 22:1205\u20131218. https:\/\/doi.org\/10.1002\/jcc.1078","journal-title":"J Comput Chem"},{"key":"11022_CR28","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1007\/bf00355047","volume":"10","author":"DM Van Aalten","year":"1996","unstructured":"Van Aalten DM, Bywater R, Findlay JB, Hendlich M, Hooft RW, Vriend G (1996) PRODRG, a program for generating molecular topologies and unique molecular descriptors from coordinates of small molecules. J Comput Aided Mol Des 10:255\u2013262. https:\/\/doi.org\/10.1007\/bf00355047","journal-title":"J Comput Aided Mol Des"},{"key":"11022_CR29","doi-asserted-by":"publisher","first-page":"9954","DOI":"10.1021\/jp003020w","volume":"105","author":"P Mark","year":"2001","unstructured":"Mark P, Nilsson L (2001) Structure and dynamics of the TIP3P, SPC, and SPC\/E water models at 298 K. J Phys Chem A 105:9954\u20139960. https:\/\/doi.org\/10.1021\/jp003020w","journal-title":"J Phys Chem A"},{"key":"11022_CR30","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","volume":"14","author":"W Humphrey","year":"1996","unstructured":"Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. J Mol Graph 14:33\u201338. https:\/\/doi.org\/10.1016\/0263-7855(96)00018-5","journal-title":"J Mol Graph"},{"key":"11022_CR31","unstructured":"Turner P (2005) XMGRACE, Version 5.1. 19. Center for Coastal and Land-Margin Research, Oregon Graduate Institute of Science & Technology, Beaverton, OR."},{"key":"11022_CR32","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1504\/IJAPR.2016.079733","volume":"3","author":"A Tharwat","year":"2016","unstructured":"Tharwat A (2016) Principal component analysis-a tutorial. Int J Appl Pattern Recognit 3:197\u2013240. https:\/\/doi.org\/10.1504\/IJAPR.2016.079733","journal-title":"Int J Appl Pattern Recognit"},{"key":"11022_CR33","doi-asserted-by":"publisher","DOI":"10.1063\/1.3268625","author":"DG Oblinsky","year":"2009","unstructured":"Oblinsky DG, VanSchouwen B, Gordon HL, Rothstein SM (2009) Procrustean rotation in concert with principal component analysis of molecular dynamics trajectories: quantifying global and local differences between conformational samples. J Chem Phys. https:\/\/doi.org\/10.1063\/1.3268625","journal-title":"J Chem Phys"},{"key":"11022_CR34","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/j.jmgm.2009.01.006","volume":"27","author":"E Papaleo","year":"2009","unstructured":"Papaleo E, Mereghetti P, Fantucci P, Grandori R, De Gioia L (2009) Free-energy landscape, principal component analysis, and structural clustering to identify representative conformations from molecular dynamics simulations: the myoglobin case. J Mol Graph Model 27:889\u2013899. https:\/\/doi.org\/10.1016\/j.jmgm.2009.01.006","journal-title":"J Mol Graph Model"},{"key":"11022_CR35","doi-asserted-by":"publisher","first-page":"29040","DOI":"10.1038\/srep29040","volume":"6","author":"VM Burger","year":"2016","unstructured":"Burger VM, Arenas DJ, Stultz CM (2016) A structure-free method for quantifying conformational flexibility in proteins. Sci Rep 6:29040. https:\/\/doi.org\/10.1038\/srep29040","journal-title":"Sci Rep"},{"key":"11022_CR36","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1002\/prot.24413","volume":"82","author":"JM Martins","year":"2014","unstructured":"Martins JM, Ramos RM, Pimenta AC, Moreira IS (2014) Solvent-accessible surface area: how well can be applied to hot-spot detection? Proteins 82:479\u2013490. https:\/\/doi.org\/10.1002\/prot.24413","journal-title":"Proteins"},{"key":"11022_CR37","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1021\/jm100087s","volume":"53","author":"B Kuhn","year":"2010","unstructured":"Kuhn B, Mohr P, Stahl M (2010) Intramolecular hydrogen bonding in medicinal chemistry. J Med Chem 53:2601\u20132611. https:\/\/doi.org\/10.1021\/jm100087s","journal-title":"J Med Chem"},{"key":"11022_CR38","volume-title":"Protein-ligand interactions: from molecular recognition to drug design","author":"R Mannhold","year":"2006","unstructured":"Mannhold R, Kubinyi H, Folkers G (2006) Protein-ligand interactions: from molecular recognition to drug design. John Wiley, Hoboken"},{"key":"11022_CR39","doi-asserted-by":"publisher","DOI":"10.1063\/1.4885338","author":"F Sittel","year":"2014","unstructured":"Sittel F, Jain A, Stock G (2014) Principal component analysis of molecular dynamics: on the use of Cartesian vs internal coordinates. J Chem Phys. https:\/\/doi.org\/10.1063\/1.4885338","journal-title":"J Chem Phys"}],"container-title":["Molecular Diversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11030-024-11022-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11030-024-11022-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11030-024-11022-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T13:03:20Z","timestamp":1758719000000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11030-024-11022-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,29]]},"references-count":39,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["11022"],"URL":"https:\/\/doi.org\/10.1007\/s11030-024-11022-4","relation":{},"ISSN":["1381-1991","1573-501X"],"issn-type":[{"value":"1381-1991","type":"print"},{"value":"1573-501X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,29]]},"assertion":[{"value":"8 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}]}}