{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T19:03:04Z","timestamp":1779822184437,"version":"3.53.1"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008809","name":"University of Hail","doi-asserted-by":"publisher","award":["RCP\u201024012"],"award-info":[{"award-number":["RCP\u201024012"]}],"id":[{"id":"10.13039\/501100008809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Colorectal cancer (CRC) is the leading cause of cancer\u2010related deaths worldwide. Colon adenocarcinoma (COAD), the most common histological subtype, is characterized by a poor prognosis in advanced stages due to significant molecular heterogeneity. Protein kinase C delta (PKC\u03b4), encoded by PRKCD, is a context\u2010dependent regulatory kinase in tumor biology. Its expression, genomic alterations, and binding interactions with phytochemicals from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Phoenix dactylifera<\/jats:italic>\n                    <\/jats:styled-content>\n                    were studied using a comprehensive in silico approach. PRKCD was found to be downregulated in all TCGA\u2010COAD tumor subgroups when compared to normal tissue. The survival analysis failed to show a statistically significant association between PRKCD expression and overall or disease\u2010free survival; thus, the protein is more likely to be a biological modulator than a prognostic marker. Mutational profiling revealed missense substitutions and copy number variations in COAD. The drug\u2010like properties of 46 phytochemicals from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. dactylifera<\/jats:italic>\n                    <\/jats:styled-content>\n                    were evaluated, and only five compounds passed all the filters. Docking against the C2 regulatory domain of PKC\u03b4 (PDB ID: 1YRK) revealed (Z)\u20104\u2010Methoxy\u20103,3\u2032,5,5\u2032\u2010tetrahydroxystilbene (PubChem CID: 13499471) as the highest\u2010scoring ligand at \u22127.0\u2009kcal\/mol. Rottlerin, the validated PKC\u03b4 inhibitor, was used as a positive control and had a score of \u22127.3\u2009kcal\/mol at the same binding site. Both complexes were subjected to 100\u2009ns molecular dynamics (MD) simulations under equated conditions. Several parameters, including backbone RMSD, RMSF, radius of gyration (Rg), solvent\u2010accessible surface area (SASA), hydrogen\u2010bond counts, principal component analysis (PCA), and free\u2010energy landscape (FEL) profiling, all indicated stable conformations for the two complexes. The lead phytocompound showed very similar behaviour to the positive control, thereby reinforcing its potential as a PRKCD modulator. The results indicate that further experimental studies on\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. dactylifera<\/jats:italic>\n                    <\/jats:styled-content>\n                    \u2010derived stilbenoids in COAD are warranted.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70302","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T14:52:26Z","timestamp":1777474346000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Multi\u2010Omics and Molecular Simulations Identify\n                    <scp>PRKCD<\/scp>\n                    as a Biological Modulator in Colon Adenocarcinoma: Validation With\n                    <i>Phoenix dactylifera<\/i>\n                    Phytochemicals and Comparison With Rottlerin"],"prefix":"10.1111","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7080-6822","authenticated-orcid":false,"given":"Mohd","family":"Adnan","sequence":"first","affiliation":[{"name":"Department of Biology, College of Science University of Ha'il  Ha'il Saudi Arabia"},{"name":"Medical and Diagnostic Research Centre University of Ha'il  Ha'il Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6236-0920","authenticated-orcid":false,"given":"Arif Jamal","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science University of Ha'il  Ha'il Saudi Arabia"},{"name":"Medical and Diagnostic Research Centre University of Ha'il  Ha'il Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mousa","family":"Alreshidi","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science University of Ha'il  Ha'il Saudi Arabia"},{"name":"Medical and Diagnostic Research Centre University of Ha'il  Ha'il Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7609-3026","authenticated-orcid":false,"given":"Malvi","family":"Surti","sequence":"additional","affiliation":[{"name":"Research and Development Cell (RDC) Parul Institute of Applied Sciences, Parul University  Vadodara Gujarat India"},{"name":"Department of Biotechnology, Parul Institute of Applied Sciences Parul University  Vadodara Gujarat India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9283-2124","authenticated-orcid":false,"given":"Mitesh","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Faculty of Engineering and Technology Marwadi University  Rajkot Gujarat India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.3892\/mco.2021.2433"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.01.001"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lddd.2025.100043"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.0106"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11130\u2010024\u201001162\u20101"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2022.01.001"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14173536"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14071732"},{"key":"e_1_2_15_10_1","first-page":"42","article-title":"Expression and Clinical Significance of PRKCD in Liver Hepatocellular Carcinoma Analyzed Based on 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