{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T11:19:08Z","timestamp":1783163948834,"version":"3.54.6"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"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"],"DOI":"10.1007\/s11030-025-11462-6","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T12:37:23Z","timestamp":1768394243000},"page":"5759-5772","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of novel PI3K\u03b1 inhibitors for colon cancer treatment via virtual screening, molecular dynamics simulation, and in vitro activity validation"],"prefix":"10.1007","volume":"30","author":[{"given":"Yu-Chen","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Long","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Yun","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou-Lan","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"11462_CR1","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","volume":"170","author":"DA Fruman","year":"2017","unstructured":"Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT (2017) The PI3K pathway in human disease. Cell 170:605\u2013635. https:\/\/doi.org\/10.1016\/j.cell.2017.07.029","journal-title":"Cell"},{"key":"11462_CR2","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1038\/nrd4204","volume":"13","author":"DA Fruman","year":"2014","unstructured":"Fruman DA, Rommel C (2014) PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov 13:140\u2013156. https:\/\/doi.org\/10.1038\/nrd4204","journal-title":"Nat Rev Drug Discov"},{"key":"11462_CR3","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s10555-009-9198-3","volume":"28","author":"MA Knowles","year":"2009","unstructured":"Knowles MA, Platt FM, Ross RL, Hurst CD (2009) Phosphatidylinositol 3-kinase (PI3K) pathway activation in bladder cancer. Cancer Metastasis Rev 28:305\u2013316. https:\/\/doi.org\/10.1007\/s10555-009-9198-3","journal-title":"Cancer Metastasis Rev"},{"key":"11462_CR4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3892\/ijo.2016.3771","volume":"50","author":"SH Sahlberg","year":"2017","unstructured":"Sahlberg SH, Mortensen AC, Hagl\u00f6f J et al (2017) Different functions of AKT1 and AKT2 in molecular pathways, cell migration and metabolism in colon cancer cells. Int J Oncol 50:5\u201314. https:\/\/doi.org\/10.3892\/ijo.2016.3771","journal-title":"Int J Oncol"},{"key":"11462_CR5","doi-asserted-by":"publisher","unstructured":"Jiang W, Ji M (2019) Receptor tyrosine kinases in PI3K signaling: the therapeutic targets in cancer. In: Seminars in cancer biology, pp 3\u201322. https:\/\/doi.org\/10.1016\/j.semcancer.2019.03.006","DOI":"10.1016\/j.semcancer.2019.03.006"},{"key":"11462_CR6","doi-asserted-by":"publisher","first-page":"1149478","DOI":"10.3389\/fphar.2023.1149478","volume":"14","author":"C Zhang","year":"2023","unstructured":"Zhang C, Cao Y, Zuo Y, Cheng H et al (2023) Bruceine a exerts antitumor effect against colon cancer by accumulating ROS and suppressing PI3K\/Akt pathway. Front Pharmacol 14:1149478. https:\/\/doi.org\/10.3389\/fphar.2023.1149478","journal-title":"Front Pharmacol"},{"key":"11462_CR7","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1126\/science.1096502","volume":"304","author":"Y Samuels","year":"2004","unstructured":"Samuels Y, Wang Z, Bardelli A et al (2004) High frequency of mutations of the PIK3CA gene in human cancers. Science 304:554. https:\/\/doi.org\/10.1126\/science.1096502","journal-title":"Science"},{"key":"11462_CR8","doi-asserted-by":"publisher","first-page":"154015","DOI":"10.1016\/j.phymed.2022.154015","volume":"99","author":"Y Zuo","year":"2022","unstructured":"Zuo Y, Zhang CZ, Ren Q et al (2022) Activation of mitochondrial-associated apoptosis signaling pathway and inhibition of PI3K\/Akt\/mTOR signaling pathway by voacamine suppress breast cancer progression. Phytomedicine 99:154015. https:\/\/doi.org\/10.1016\/j.phymed.2022.154015","journal-title":"Phytomedicine"},{"key":"11462_CR9","doi-asserted-by":"publisher","first-page":"101430","DOI":"10.1016\/j.gendis.2024.101430","volume":"12","author":"Y Wang","year":"2025","unstructured":"Wang Y, Rozen V, Zhao Y, Wang Z (2025) Oncogenic activation of PIK3CA in cancers: emerging targeted therapies in precision oncology. Genes Dis 12:101430. https:\/\/doi.org\/10.1016\/j.gendis.2024.101430","journal-title":"Genes Dis"},{"key":"11462_CR10","doi-asserted-by":"publisher","first-page":"111718","DOI":"10.1016\/j.ejmech.2019.111718","volume":"183","author":"FM Elmenier","year":"2019","unstructured":"Elmenier FM, Lasheen DS, Abouzid KAM (2019) Phosphatidylinositol 3 kinase (PI3K) inhibitors as new weapon to combat cancer. Eur J Med Chem 183:111718. https:\/\/doi.org\/10.1016\/j.ejmech.2019.111718","journal-title":"Eur J Med Chem"},{"key":"11462_CR11","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.jare.2024.03.002","volume":"68","author":"C Liu","year":"2025","unstructured":"Liu C, Cao Y, Zuo Y et al (2025) Hybridization-based discovery of novel quinazoline-2-indolinone derivatives as potent and selective PI3K\u03b1 inhibitors. J Adv Res 68:459\u2013475. https:\/\/doi.org\/10.1016\/j.jare.2024.03.002","journal-title":"J Adv Res"},{"key":"11462_CR12","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.semcancer.2019.02.002","volume":"59","author":"R Arafeh","year":"2019","unstructured":"Arafeh R, Samuels Y (2019) PIK3CA in cancer: the past 30 years. Semin Cancer Biol 59:36\u201349. https:\/\/doi.org\/10.1016\/j.semcancer.2019.02.002","journal-title":"Semin Cancer Biol"},{"key":"11462_CR13","doi-asserted-by":"publisher","first-page":"2150","DOI":"10.1038\/s41416-023-02221-1","volume":"128","author":"C Belli","year":"2023","unstructured":"Belli C, Repetto M, Anand S et al (2023) The emerging role of PI3K inhibitors for solid tumour treatment and beyond. Br J Cancer 128:2150\u20132162. https:\/\/doi.org\/10.1038\/s41416-023-02221-1","journal-title":"Br J Cancer"},{"key":"11462_CR14","doi-asserted-by":"publisher","first-page":"105900","DOI":"10.1016\/j.phrs.2021.105900","volume":"173","author":"D Meng","year":"2021","unstructured":"Meng D, He W, Zhang Y, Liang Z, Zheng J, Zhang X, Zheng X, Zhan P, Chen H, Li W, Cai L (2021) Development of PI3K inhibitors: advances in clinical trials and new strategies. Pharmacol Res 173:105900. https:\/\/doi.org\/10.1016\/j.phrs.2021.105900","journal-title":"Pharmacol Res"},{"key":"11462_CR15","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1056\/NEJMoa2404625","volume":"391","author":"NC Turner","year":"2024","unstructured":"Turner NC, Im SA, Saura C et al (2024) Inavolisib-based therapy in PIK3CA-mutated advanced breast cancer N. Engl J Med 391:1584\u20131596. https:\/\/doi.org\/10.1056\/NEJMoa2404625","journal-title":"Engl J Med"},{"key":"11462_CR16","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/s41573-021-00209-1","volume":"20","author":"B Vanhaesebroeck","year":"2021","unstructured":"Vanhaesebroeck B, Perry MWD et al (2021) PI3K inhibitors are finally coming of age. Nat Rev Drug Dis 20:741\u2013769. https:\/\/doi.org\/10.1038\/s41573-021-00209-1","journal-title":"Nat Rev Drug Dis"},{"key":"11462_CR17","doi-asserted-by":"publisher","first-page":"5015","DOI":"10.1158\/1078-0432.CCR-16-2888","volume":"23","author":"D Juric","year":"2017","unstructured":"Juric D, de Bono JS, Lo Russo PM et al (2017) A first-in-human, phase I, dose-escalation study of TAK-117, a selective PI3K\u03b1 isoform inhibitor, in patients with advanced solid malignancies. Clin Cancer Res 23:5015\u20135023. https:\/\/doi.org\/10.1158\/1078-0432.CCR-16-2888","journal-title":"Clin Cancer Res"},{"key":"11462_CR18","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/nrd2926","volume":"8","author":"P Liu","year":"2009","unstructured":"Liu P, Cheng H, Roberts TM, Zhao JJ (2009) Targeting the phosphoinositide 3-Kinase pathway in cancer. Nat Rev Drug Dis 8:627\u2013644. https:\/\/doi.org\/10.1038\/nrd2926","journal-title":"Nat Rev Drug Dis"},{"key":"11462_CR19","doi-asserted-by":"publisher","first-page":"115754","DOI":"10.1016\/j.ejmech.2023.115754","volume":"260","author":"XM Zheng","year":"2023","unstructured":"Zheng XM, Chen YS, Ban YJ et al (2023) Design, synthesis and bioevaluation of PI3K\u03b1-selective inhibitors as potential colorectal cancer drugs. Eur J MedChem 260:115754. https:\/\/doi.org\/10.1016\/j.ejmech.2023.115754","journal-title":"Eur J MedChem"},{"key":"11462_CR20","doi-asserted-by":"publisher","first-page":"13568","DOI":"10.3390\/ijms232113568","volume":"23","author":"Y Zhang","year":"2022","unstructured":"Zhang Y, Luo M, Wu P, Wu S, Lee TY, Bai C (2022) Application of computational biology and artificial intelligence in drug design. Int J Mol Sci 23:13568. https:\/\/doi.org\/10.3390\/ijms232113568","journal-title":"Int J Mol Sci"},{"key":"11462_CR21","doi-asserted-by":"publisher","first-page":"100222","DOI":"10.1016\/j.slasd.2025.100222","volume":"32","author":"TS Dexheimer","year":"2025","unstructured":"Dexheimer TS, Davoudi Z, Coussens NP, Silvers T et al (2025) Combinatorial screen of targeted agents with the PI3K inhibitors inavolisib, alpelisib, duvelisib, and Copanlisib in multi-cell type tumor spheroids. SLAS Dis 32:100222. https:\/\/doi.org\/10.1016\/j.slasd.2025.100222","journal-title":"SLAS Dis"},{"key":"11462_CR22","doi-asserted-by":"publisher","first-page":"116786","DOI":"10.1016\/j.ejmech.2024.116786","volume":"277","author":"S Lian","year":"2024","unstructured":"Lian S, Du Z, Chen Q, Xia Y, Miao X, Yu W, Sun Q, Feng C (2024) From lab to clinic: the discovery and optimization journey of PI3K inhibitors. Eur J Med Chem 277:116786. https:\/\/doi.org\/10.1016\/j.ejmech.2024.116786","journal-title":"Eur J Med Chem"},{"key":"11462_CR23","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1021\/ci200528d","volume":"52","author":"T Scior","year":"2012","unstructured":"Scior T, Bender A, Tresadern G et al (2012) Recognizing pitfalls in virtual screening: a critical review. J Chem Inf Model 52:867\u2013881. https:\/\/doi.org\/10.1021\/ci200528d","journal-title":"J Chem Inf Model"},{"key":"11462_CR24","doi-asserted-by":"publisher","first-page":"951","DOI":"10.2174\/1570180819666220405225817","volume":"19","author":"IJS Nascimento","year":"2022","unstructured":"Nascimento IJS, de Aquino TM, da Silva-J\u00fanior EF (2022) The new era of drug discovery: the power of computer-aided drug design (CADD). Lett Drug Des Discov 19:951\u2013955. https:\/\/doi.org\/10.2174\/1570180819666220405225817","journal-title":"Lett Drug Des Discov"},{"key":"11462_CR25","doi-asserted-by":"publisher","first-page":"3949","DOI":"10.1007\/s11030-023-10788-3","volume":"28","author":"W Zhang","year":"2024","unstructured":"Zhang W, Hu ML, Shi XY, Chen XL, Su X, Qi HZ, Yuan L, Zhang H (2024) Discovery of novel Akt1 inhibitors by an ensemble\u2013based virtual screening method, molecular dynamics simulation, and in vitro biological activity testing. Mol Divers 28:3949\u20133963. https:\/\/doi.org\/10.1007\/s11030-023-10788-3","journal-title":"Mol Divers"},{"key":"11462_CR26","doi-asserted-by":"publisher","first-page":"117162","DOI":"10.1016\/j.ejmech.2024.117162","volume":"283","author":"J Dai","year":"2025","unstructured":"Dai J, Zhou Z, Zhao Y, Kong F, Zhai Z, Zhu Z, Cai J, Huang S, Xu Y, Sun T (2025) Combined usage of ligand- and structure-based virtual screening in the artificial intelligence era. Eur J Med Chem 283:117162. https:\/\/doi.org\/10.1016\/j.ejmech.2024.117162","journal-title":"Eur J Med Chem"},{"key":"11462_CR27","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1007\/s00894-023-05504-9","volume":"29","author":"H Zhang","year":"2023","unstructured":"Zhang H, Zhang HR, Zhang J, Hu ML, Ren L, Luo QQ, Qi HZ (2023) Discovery of novel S6K1 inhibitors by an ensemble\u2013based virtual screening method and molecular dynamics simulation. J Mol Model 29:102. https:\/\/doi.org\/10.1007\/s00894-023-05504-9","journal-title":"J Mol Model"},{"key":"11462_CR28","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s10822-024-00580-2","volume":"38","author":"H Zhang","year":"2024","unstructured":"Zhang H, Qi HZ, Li YJ, Shi XY, Hu ML, Chen XL (2024) Identifcation of novel inhibitors targeting PI3K\u03b1 via ensemble\u2013based virtual screening method, biological evaluation and molecular dynamics simulation. J Comput Aided Mol Des 38:37. https:\/\/doi.org\/10.1007\/s10822-024-00580-2","journal-title":"J Com Aided Mol Des"},{"key":"11462_CR29","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1002\/jcc.20291","volume":"26","author":"DD Van Der Spoel","year":"2005","unstructured":"Van Der Spoel DD, Lindah E, Hess B, Groenhof G, Mark AE, Berendsen HJ (2005) GROMACS: fast, fexible, and free. J Comput Chem 26:1701\u20131718","journal-title":"J Comput Chem"},{"key":"11462_CR30","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.3390\/molecules25081971","volume":"25","author":"G Poli","year":"2005","unstructured":"Poli G, Granchi C, Rizzolio F, Tuccinardi T (2005) Application of MM-PBSA methods in virtual screening. Molecules 25:1971. https:\/\/doi.org\/10.3390\/molecules25081971","journal-title":"Molecules"},{"key":"11462_CR31","doi-asserted-by":"publisher","first-page":"5840","DOI":"10.1158\/0008-5472.CAN-06-4615","volume":"67","author":"FI Raynaud","year":"2007","unstructured":"Raynaud FI, Eccles S, Clarke PA, Hayes A, Nutley B, Alix S, Henley A, Di-Stefano F, Ahmad Z, Guillard S, Bjerke LM, Kelland L, Valenti M, Patterson L, Gowan S, Brandon AH, Hayakawa M, Kaizawa H, Koizumi T, akahide Ohishi A, Patel S, Saghir N, Parker P, Waterfield M, Workman P (2007) Pharmacologic characterization of a potent inhibitor of class I phosphatidylinositide 3-kinases. Cancer Res 67:5840\u20135850. https:\/\/doi.org\/10.1158\/0008-5472.CAN-06-4615","journal-title":"Cancer Res"},{"key":"11462_CR32","doi-asserted-by":"publisher","first-page":"2146","DOI":"10.1158\/0008-5472.CAN-09-4355","volume":"70","author":"P Workman","year":"2010","unstructured":"Workman P, Clarke PA, Raynaud FI, Montfort RLM (2010) Drugging the PI3 kinome: from chemical tools to drugs in the. Clin Cancer Res 70:2146\u20132157. https:\/\/doi.org\/10.1158\/0008-5472.CAN-09-4355","journal-title":"Clin Cancer Res"}],"container-title":["Molecular Diversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11030-025-11462-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11030-025-11462-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11030-025-11462-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T10:39:13Z","timestamp":1783161553000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11030-025-11462-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,14]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["11462"],"URL":"https:\/\/doi.org\/10.1007\/s11030-025-11462-6","relation":{},"ISSN":["1573-501X"],"issn-type":[{"value":"1573-501X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,14]]},"assertion":[{"value":"17 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2026","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 financial interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}