{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:43:37Z","timestamp":1790052217558,"version":"4.0.1"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech and App Biochem"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Dual inhibition of Akt and MEK1 pathways offers a promising strategy to enhance treatment efficacy in gastric cancer. In this study, we employed computational approaches followed by in vitro validations. Our results demonstrate that SBL\u2010027 exhibits robust and enduring interactions with Akt and MEK1 kinases, as evidenced by atomistic molecular dynamics simulations and molecular mechanics Poisson\u2013Boltzmann surface area (MM\u2010PBSA) based binding free energy estimates. The predicted Gibbs binding free energies indicate highly favorable interactions between SBL\u2010027 and both Akt and MEK1 kinases. In vitro, SBL\u2010027 displayed an IC<jats:sub>50<\/jats:sub> value of 195.20\u00a0nM against Akt and 239.10\u00a0nM against MEK1 enzymes. The compound exhibited potent inhibition of cell proliferation in KATOIII and SNU\u20105 cells, with GI<jats:sub>50<\/jats:sub> values of 490.70 and 615.14\u00a0nM, respectively. Moreover, SBL\u2010027 induced an increase in the sub G<jats:sub>0<\/jats:sub>\/G<jats:sub>1<\/jats:sub> population during the cell cycle of KATOIII and SNU\u20105 cells, while facilitating early and late\u2010phase apoptosis in these cell lines. Notably, the compound significantly reduced the percentage of dual\u2010positive cells expressing both MEK1 and Akt in gastric cancer cells. The strong binding affinity, stability, and favorable thermodynamics of SBL\u2010027 along with the established in vitro efficacy highlight its potential as a lead compound for further preclinical and clinical development.<\/jats:p>","DOI":"10.1002\/bab.2716","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T22:46:46Z","timestamp":1736290006000},"page":"1006-1017","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dual Targeting of MEK1 and Akt Kinase Identified SBL\u2010027 as a Promising Lead Candidate to Control Cell Proliferations in Gastric Cancer"],"prefix":"10.1002","volume":"72","author":[{"given":"Maha Alamodi","family":"Alghamdi","sequence":"first","affiliation":[{"name":"Department of Surgery, College of Medicine King Khalid University  Abha Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6739-4014","authenticated-orcid":false,"given":"Hemali","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine King Khalid University  Abha Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.5114\/pg.2018.80001"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.32074\/1591\u2010951x\u2010166"},{"issue":"4","key":"e_1_2_12_4_1","first-page":"175","article-title":"Gastric Cancer: Prevention, Risk Factors and Treatment","volume":"4","author":"Zali H.","year":"2011","journal-title":"Gastroenterol Hepatol Bed Bench"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.811258"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.628690"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.819128"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010021\u201000828\u20105"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.245"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21707"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers6031441"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1372330"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2020.8454"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.652"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100296"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12195\u2010021\u201000694\u20109"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756\u20108722\u20103\u20108"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43556\u2010022\u201000110\u20102"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1271268"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.768861"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201001190\u2010w"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073847"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.advenzreg.2006.01.004"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1045521"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512222"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2107207118"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15123248"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102760\u20104"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012913"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032\u2010022\u201001846\u20101"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv315"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.1c00645"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3727\/096504021\u00d716281573507558"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25031848"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15030703"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2016.12.008"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8091013"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i24.2567"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nou058"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00733"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.32604\/or.2022.025187"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.4103\/jcrt.JCRT_228_17"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v14.i1.76"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.2147\/cmar.S244481"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14030230"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.4149\/neo_2014_019"}],"container-title":["Biotechnology and Applied Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bab.2716","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T07:20:14Z","timestamp":1754896814000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/bab.2716"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,7]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/bab.2716"],"URL":"https:\/\/doi.org\/10.1002\/bab.2716","archive":["Portico"],"relation":{},"ISSN":["0885-4513","1470-8744"],"issn-type":[{"value":"0885-4513","type":"print"},{"value":"1470-8744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,7]]},"assertion":[{"value":"2024-06-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}