{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T14:35:01Z","timestamp":1762353301232,"version":"build-2065373602"},"reference-count":56,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,19]],"date-time":"2022-11-19T00:00:00Z","timestamp":1668816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PJ_MIN_SALUTE_METODI_SOSTITUTIVI","award":["CUP: B75F21002350001","J_RIC_FFABR_2022_005832"],"award-info":[{"award-number":["CUP: B75F21002350001","J_RIC_FFABR_2022_005832"]}]},{"name":"University of Palermo","award":["CUP: B75F21002350001","J_RIC_FFABR_2022_005832"],"award-info":[{"award-number":["CUP: B75F21002350001","J_RIC_FFABR_2022_005832"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In vitro antiproliferative assays still represent one of the most important tools in the anticancer drug discovery field, especially to gain insights into the mechanisms of action of anticancer small molecules. The NCI-DTP (National Cancer Institute Developmental Therapeutics Program) undoubtedly represents the most famous project aimed at rapidly testing thousands of compounds against multiple tumor cell lines (NCI60). The large amount of biological data stored in the National Cancer Institute (NCI) database and many other databases has led researchers in the fields of computational biology and medicinal chemistry to develop tools to predict the anticancer properties of new agents in advance. In this work, based on the available antiproliferative data collected by the NCI and the manipulation of molecular descriptors, we propose the new in silico Antiproliferative Activity Predictor (AAP) tool to calculate the GI50 values of input structures against the NCI60 panel. This ligand-based protocol, validated by both internal and external sets of structures, has proven to be highly reliable and robust. The obtained GI50 values of a test set of 99 structures present an error of less than \u00b11 unit. The AAP is more powerful for GI50 calculation in the range of 4\u20136, showing that the results strictly correlate with the experimental data. The encouraging results were further supported by the examination of an in-house database of curcumin analogues that have already been studied as antiproliferative agents. The AAP tool identified several potentially active compounds, and a subsequent evaluation of a set of molecules selected by the NCI for the one-dose\/five-dose antiproliferative assays confirmed the great potential of our protocol for the development of new anticancer small molecules. The integration of the AAP tool in the free web service DRUDIT provides an interesting device for the discovery and\/or optimization of anticancer drugs to the medicinal chemistry community. The training set will be updated with new NCI-tested compounds to cover more chemical spaces, activities, and cell lines. Currently, the same protocol is being developed for predicting the TGI (total growth inhibition) and LC50 (median lethal concentration) parameters to estimate toxicity profiles of small molecules.<\/jats:p>","DOI":"10.3390\/ijms232214374","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T02:52:21Z","timestamp":1668999141000},"page":"14374","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Antiproliferative Activity Predictor: A New Reliable In Silico Tool for Drug Response Prediction against NCI60 Panel"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9560-1882","authenticated-orcid":false,"given":"Annamaria","family":"Martorana","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche \u201cSTEBICEF\u201d, Universit\u00e0 Degli Studi di Palermo, Viale Delle Scienze Ed. 17, I-90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6510-1943","authenticated-orcid":false,"given":"Gabriele","family":"La Monica","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche \u201cSTEBICEF\u201d, Universit\u00e0 Degli Studi di Palermo, Viale Delle Scienze Ed. 17, I-90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9283-4920","authenticated-orcid":false,"given":"Alessia","family":"Bono","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche \u201cSTEBICEF\u201d, Universit\u00e0 Degli Studi di Palermo, Viale Delle Scienze Ed. 17, I-90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Mannino","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche \u201cSTEBICEF\u201d, Universit\u00e0 Degli Studi di Palermo, Viale Delle Scienze Ed. 17, I-90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvestre","family":"Buscemi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche \u201cSTEBICEF\u201d, Universit\u00e0 Degli Studi di Palermo, Viale Delle Scienze Ed. 17, I-90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4402-5798","authenticated-orcid":false,"given":"Antonio","family":"Palumbo Piccionello","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche \u201cSTEBICEF\u201d, Universit\u00e0 Degli Studi di Palermo, Viale Delle Scienze Ed. 17, I-90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5861-3342","authenticated-orcid":false,"given":"Carla","family":"Gentile","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche \u201cSTEBICEF\u201d, Universit\u00e0 Degli Studi di Palermo, Viale Delle Scienze Ed. 17, I-90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5116-6815","authenticated-orcid":false,"given":"Antonino","family":"Lauria","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche \u201cSTEBICEF\u201d, Universit\u00e0 Degli Studi di Palermo, Viale Delle Scienze Ed. 17, I-90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8763-7199","authenticated-orcid":false,"given":"Daniele","family":"Peri","sequence":"additional","affiliation":[{"name":"Dipartimento di Ingegneria Dell\u2019innovazione Industriale e Digitale, Universit\u00e0 Degli Studi di Palermo, Viale Delle Scienze Ed. 6, I-90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/nrc1951","article-title":"The NCI60 human tumour cell line anticancer drug screen","volume":"6","author":"Shoemaker","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nature11003","article-title":"The cancer cell line encyclopedia enables predictive modelling of anticancer drug sensitivity","volume":"483","author":"Barretina","year":"2012","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"D955","DOI":"10.1093\/nar\/gks1111","article-title":"Genomics of Drug Sensitivity in Cancer (GDSC): A resource for therapeutic biomarker discovery in cancer cells","volume":"41","author":"Yang","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_4","first-page":"A68","article-title":"The Cancer Genome Atlas (TCGA): An immeasurable source of knowledge","volume":"19","author":"Tomczak","year":"2015","journal-title":"Contemp. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.cell.2013.08.003","article-title":"An interactive resource to identify cancer genetic and lineage dependencies targeted by small molecules","volume":"154","author":"Basu","year":"2013","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1093\/jnci\/djt007","article-title":"The clinical relevance of cancer cell lines","volume":"105","author":"Gillet","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mirabelli, P., Coppola, L., and Salvatore, M. (2019). Cancer cell lines are useful model systems for medical research. Cancers, 11.","DOI":"10.3390\/cancers11081098"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1158\/1541-7786.MCR-15-0189","article-title":"Tumor-derived cell lines as molecular models of cancer pharmacogenomics","volume":"14","author":"Goodspeed","year":"2016","journal-title":"Mol. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1007\/s00280-003-0623-y","article-title":"Anticancer drug development at the US National Cancer Institute","volume":"52","author":"Takimoto","year":"2003","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_10","unstructured":"(2022, November 17). NCI-60 Human Tumor Cell Lines Screen\u2014Introduction, Available online: https:\/\/dtp.cancer.gov\/discovery_development\/nci-60\/."},{"key":"ref_11","unstructured":"(2022, November 17). Molecular Characterization of the NCI-60, Available online: https:\/\/dtp.cancer.gov\/discovery_development\/nci-60\/characterization.htm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1158\/1535-7163.MCT-06-0787","article-title":"Anticancer medicines in development: Assessment of bioactivity profiles within the National Cancer Institute anticancer screening data","volume":"6","author":"Covell","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"ref_13","unstructured":"(2022, November 17). NCI60 Human Timor Cell Lines Screen\u2014Cell Lines in the In Vitro Screen, Available online: https:\/\/dtp.cancer.gov\/discovery_development\/nci-60\/cell_list.htm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"bbab408","DOI":"10.1093\/bib\/bbab408","article-title":"An overview of machine learning methods for monotherapy drug response prediction","volume":"23","author":"Firoozbakht","year":"2021","journal-title":"Brief. Bioinform."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1093\/jnci\/81.14.1088","article-title":"Display and analysis of patterns of differential activity of drugs against human tumor cell lines: Development of mean graph and COMPARE algorithm","volume":"81","author":"Paull","year":"1989","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S1093-3263(01)00126-7","article-title":"COMPARE: A web accessible tool for investigating mechanisms of cell growth inhibition","volume":"20","author":"Zaharevitz","year":"2002","journal-title":"J. Mol. Graph. Model."},{"key":"ref_17","unstructured":"(2022, November 17). NCI-60 Analysis Tools\u2014CellMiner, Available online: http:\/\/discover.nci.nih.gov\/cellminer\/."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3499","DOI":"10.1158\/0008-5472.CAN-12-1370","article-title":"CellMiner: A web-based suite of genomic and pharmacologic tools to explore transcript and drug patterns in the NCI-60 cell line set","volume":"72","author":"Reinhold","year":"2012","journal-title":"Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"D1083","DOI":"10.1093\/nar\/gkaa968","article-title":"CellMiner Cross-Database (CellMinerCDB) version 1.2: Exploration of patient-derived cancer cell line pharmacogenomics","volume":"49","author":"Luna","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lind, A.P., and Anderson, P.C. (2019). Predicting drug activity against cancer cells by random forest models based on minimal genomic information and chemical properties. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0219774"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhang, N., Wang, H., Fang, Y., Wang, J., Zheng, X., and Liu, X.S. (2015). Predicting anticancer drug responses using a dual-layer integrated cell line-drug network model. PLoS Comput. Biol., 11.","DOI":"10.1371\/journal.pcbi.1004498"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"W502","DOI":"10.1093\/nar\/gkaa327","article-title":"PaccMann: A web service for interpretable anticancer compound sensitivity prediction","volume":"48","author":"Cadow","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8857","DOI":"10.1038\/s41598-018-27214-6","article-title":"Cancer Drug Response Profile scan (CDRscan): A deep learning model that predicts drug effectiveness from cancer genomic signature","volume":"8","author":"Chang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Joo, M., Park, A., Kim, K., Son, W.J., Lee, H.S., Lim, G., Lee, J., Lee, D.H., An, J., and Kim, J.H. (2019). A deep learning model for cell growth inhibition IC50 prediction and its application for gastric cancer patients. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246276"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1021\/acs.jcim.1c00168","article-title":"pdCSM-cancer: Using graph-based signatures to identify small molecules with anticancer properties","volume":"61","author":"Pires","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4274","DOI":"10.1016\/j.ejmech.2011.06.033","article-title":"Virtual lock-and-key approach: The in silico revival of Fischer model by means of molecular descriptors","volume":"46","author":"Lauria","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ejmech.2014.01.025","article-title":"Multivariate analysis in the identification of biological targets for designed molecular structures: The BIOTA protocol","volume":"75","author":"Lauria","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1093\/bioinformatics\/btz783","article-title":"DRUDIT: Web-based DRUgs DIscovery Tools to design small molecules as modulators of biological targets","volume":"36","author":"Lauria","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.ejmech.2013.01.019","article-title":"New annelated thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidines, with potent anticancer activity, designed through VLAK protocol","volume":"62","author":"Lauria","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.ejmech.2012.07.046","article-title":"Lead optimization through VLAK protocol: New annelated pyrrolo-pyrimidine derivatives as antitumor agents","volume":"55","author":"Lauria","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3424","DOI":"10.1021\/jm4002023","article-title":"Synthesis and biological activities of a new class of heat shock protein 90 inhibitors, designed by energy-based pharmacophore virtual screening","volume":"56","author":"Lauria","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1016\/j.tet.2011.01.056","article-title":"Nucleophilic substitutions in the isoindole series as a valuable tool to synthesize derivatives with antitumor activity","volume":"67","author":"Diana","year":"2011","journal-title":"Tetrahedron"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.ejmech.2013.03.046","article-title":"Exploring the anticancer potential of pyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-one derivatives: The effect on apoptosis induction, cell cycle and proliferation","volume":"64","author":"Mingoia","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_34","unstructured":"Kayed, R., Lo Cascio, F., Piccionello Palumbo, A., and Pace, A. (2020). Novel Small Molecules That Bind and\/or Modulate Different Forms of Tau Oligomers. (WO2020\/219714 A1), Patent."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31714","DOI":"10.1039\/C7RA05300B","article-title":"Curcumin-like compounds designed to modify amyloid beta peptide aggregation patterns","volume":"7","author":"Battisti","year":"2017","journal-title":"RSC Adv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19011","DOI":"10.1038\/s41598-019-55419-w","article-title":"Toxic tau oligomers modulated by novel curcumin derivatives","volume":"9","author":"Puangmalai","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lauria, A., Martorana, A., La Monica, G., Mannino, S., Mannino, G., Peri, D., and Gentile, C. (2021). In silico identification of small molecules as new Cdc25 inhibitors through the correlation between chemosensitivity and protein expression pattern. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073714"},{"key":"ref_38","unstructured":"(2022, November 17). NCI DTP Chemical Data, Available online: https:\/\/wiki.nci.nih.gov\/display\/NCIDTPdata\/Chemical+Data."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1016\/j.ejca.2005.05.009","article-title":"Curcumin: The story so far","volume":"41","author":"Sharma","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"174266","DOI":"10.1016\/j.ejphar.2021.174266","article-title":"Perspectives for synthetic curcumins in chemoprevention and treatment of cancer: An update with promising analogues","volume":"906","author":"Adeluola","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4166","DOI":"10.1007\/s00044-015-1457-y","article-title":"Synthesis, antiproliferative activity, and molecular docking studies of curcumin analogues bearing pyrazole ring","volume":"24","author":"Ahsan","year":"2015","journal-title":"Med. Chem. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.7314\/APJCP.2016.17.4.1739","article-title":"Evaluation of anticancer activity of curcumin analogues bearing a heterocyclic nucleus","volume":"17","author":"Ahsan","year":"2016","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1021\/mp700113r","article-title":"Bioavailability of curcumin: Problems and promises","volume":"4","author":"Anand","year":"2007","journal-title":"Mol. Pharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.tifs.2021.02.006","article-title":"Recent advances to improve curcumin oral bioavailability","volume":"110","author":"Sabet","year":"2021","journal-title":"Trends Food Sci. Technol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1146\/annurev-food-032818-121738","article-title":"Curcumin: Recent advances in the development of strategies to improve oral bioavailability","volume":"10","author":"Sanidad","year":"2019","journal-title":"Annu. Rev. Food Sci. Technol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Kotha, R.R., and Luthria, D.L. (2019). Curcumin: Biological, pharmaceutical, nutraceutical, and analytical aspects. Molecules, 24.","DOI":"10.3390\/molecules24162930"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1021\/acs.jmedchem.6b00975","article-title":"The essential medicinal chemistry of curcumin","volume":"60","author":"Nelson","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s12013-020-00922-5","article-title":"An update on the pharmacological usage of curcumin: Has it failed in the drug discovery pipeline?","volume":"78","author":"Olotu","year":"2020","journal-title":"Cell Biochem. Biophys."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"105489","DOI":"10.1016\/j.phrs.2021.105489","article-title":"The potency of heterocyclic curcumin analogues: An evidence-based review","volume":"166","author":"Rodrigues","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14807","DOI":"10.1074\/jbc.RA120.014630","article-title":"Modulating disease-relevant tau oligomeric strains by small molecules","volume":"295","author":"Garcia","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1021\/ol303091m","article-title":"A cascade reaction actuated by nucleophilic heterocyclic carbene catalyzed intramolecular addition of enals via homoenolate to \u03b1,\u03b2-unsaturated esters: Efficient synthesis of coumarin derivatives","volume":"15","author":"Sinu","year":"2013","journal-title":"Org. Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/bs.aihch.2015.05.001","article-title":"Recent advances in the chemistry of 1,2,4-oxadiazoles","volume":"116","author":"Pace","year":"2015","journal-title":"Adv. Heterocycl. Chem."},{"key":"ref_53","unstructured":"(2022, November 17). NCI60 Growth Inhibition Data\u2014Download NCI Cell Line Data, Available online: https:\/\/wiki.nci.nih.gov\/display\/NCIDTPdata\/NCI-60+Growth+Inhibition+Data."},{"key":"ref_54","unstructured":"(2022, November 17). Compound Submission for NCI60 Testing\u2014Selection Guidelines, Available online: https:\/\/dtp.cancer.gov\/organization\/dscb\/compoundSubmission\/structureSelection.htm."},{"key":"ref_55","unstructured":"(2022, November 17). NCI60 Screening Methodology\u2014NCI60 Cell One\/Five Doses Screen, Available online: https:\/\/dtp.cancer.gov\/discovery_development\/nci-60\/methodology.htm."},{"key":"ref_56","unstructured":"(2022, November 17). NCI-60 Human Cancer Cell Line Screen\u2014Standard Operating Procedures for Sample Preparation for NCI60 Screen, Available online: https:\/\/dtp.cancer.gov\/discovery_development\/nci-60\/handling.htm."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14374\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:21:47Z","timestamp":1760145707000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14374"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,19]]},"references-count":56,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232214374"],"URL":"https:\/\/doi.org\/10.3390\/ijms232214374","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2022,11,19]]}}}