{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:44:59Z","timestamp":1791863099878,"version":"4.3.4"},"reference-count":37,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Molecular Graphics and Modelling"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1016\/j.jmgm.2026.109578","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:12:03Z","timestamp":1790007123000},"page":"109578","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Ligand-based pharmacophore modeling and molecular dynamics driven discovery of novel MEK1 inhibitors targeting KRAS signalling pathway"],"prefix":"10.1016","volume":"149","author":[{"given":"Krishna","family":"Kalaskar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajasekhar Reddy","family":"Alavala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.jmgm.2026.109578_bib1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-55098-7","article-title":"Co-incidence of RCC-susceptibility polymorphisms with HIF cis-acting sequences supports a pathway tuning model of cancer","volume":"9","author":"Schmid","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jmgm.2026.109578_bib2","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.ejmech.2018.12.026","article-title":"Design and development of Isatin-triazole hydrazones as potential inhibitors of microtubule affinity-regulating kinase 4 for the therapeutic management of cell proliferation and metastasis","volume":"163","author":"Aneja","year":"2019","journal-title":"Eur. J. Med. Chem."},{"issue":"1","key":"10.1016\/j.jmgm.2026.109578_bib3","first-page":"7","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. Clin."},{"issue":"3","key":"10.1016\/j.jmgm.2026.109578_bib4","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.jmgm.2026.109578_bib5","series-title":"RAS Proteins and their Regulators in Human Disease","author":"Simanshu","year":"2017"},{"key":"10.1016\/j.jmgm.2026.109578_bib6","series-title":"GEFs and GAPs: Critical Elements in the Control of Small G Proteins","author":"Bos","year":"2007"},{"key":"10.1016\/j.jmgm.2026.109578_bib7","series-title":"Targeting the PI3K\/AKT\/mTOR and RAF\/MEK\/ERK Pathways for Cancer Therapy","author":"Li","year":"2022"},{"issue":"8","key":"10.1016\/j.jmgm.2026.109578_bib8","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/s41573-020-0068-6","article-title":"RAS-targeted therapies: is the undruggable drugged?","volume":"19","author":"Moore","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"issue":"12","key":"10.1016\/j.jmgm.2026.109578_bib9","doi-asserted-by":"crossref","first-page":"4325","DOI":"10.3390\/ijms21124325","article-title":"Targeting KRAS mutant non-small-cell lung cancer: past, present and future","volume":"21","author":"Uras","year":"2020","journal-title":"Int. J. Mol. Sci."},{"issue":"32","key":"10.1016\/j.jmgm.2026.109578_bib10","doi-asserted-by":"crossref","first-page":"15823","DOI":"10.1073\/pnas.1904529116","article-title":"Drugging an undruggable pocket on KRAS","volume":"116","author":"Kessler","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"10","key":"10.1016\/j.jmgm.2026.109578_bib11","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1038\/s41591-022-02007-7","article-title":"Anti-tumor efficacy of a potent and selective non-covalent KRASG12D inhibitor","volume":"28","author":"Hallin","year":"2022","journal-title":"Nat. Med."},{"key":"10.1016\/j.jmgm.2026.109578_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.annonc.2023.10.025","article-title":"LBA33 A first-in-human phase I study of a novel KRAS G12D inhibitor HRS-4642 in patients with advanced solid tumors harboring KRAS G12D mutation","volume":"34","author":"Zhou","year":"2023","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.jmgm.2026.109578_bib13","series-title":"Structure-Based Inhibitor Design of Mutant RAS proteins\u2014a Paradigm Shift","author":"Ny\u00edri","year":"2020"},{"issue":"10","key":"10.1016\/j.jmgm.2026.109578_bib14","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1039\/D3MD00145H","article-title":"MEK inhibitors in cancer treatment: structural insights, regulation, recent advances and future perspectives","volume":"14","author":"Ram","year":"2023","journal-title":"RSC Med. Chem."},{"key":"10.1016\/j.jmgm.2026.109578_bib15","series-title":"Onco-Immunomodulatory Properties of Pharmacological Interference with RAS-RAF-MEK-ERK Pathway Hyperactivation","author":"Avery","year":"2022"},{"issue":"12","key":"10.1016\/j.jmgm.2026.109578_bib16","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/nrd4281","article-title":"Targeting RAS\u2013ERK signalling in cancer: promises and challenges","volume":"13","author":"Samatar","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"issue":"5","key":"10.1016\/j.jmgm.2026.109578_bib17","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3390\/md19050253","article-title":"Compounds identified from marine mangrove plant (Avicennia alba) as potential antiviral drug candidates against WDSV, an in-silico approach","volume":"19","author":"Aljahdali","year":"2021","journal-title":"Mar. Drugs"},{"issue":"3","key":"10.1016\/j.jmgm.2026.109578_bib18","doi-asserted-by":"crossref","first-page":"749","DOI":"10.18596\/jotcsa.927426","article-title":"Pharmacophore modeling in drug discovery: methodology and current status","volume":"8","author":"Muhammed","year":"2021","journal-title":"J. Turkish Chem. Soc. Sec. A: Chemistry"},{"issue":"3","key":"10.1016\/j.jmgm.2026.109578_bib19","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ddtec.2004.11.015","article-title":"Pharmacophore definition and 3D searches","volume":"1","author":"Langer","year":"2004","journal-title":"Drug Discov. Today Technol."},{"issue":"16","key":"10.1016\/j.jmgm.2026.109578_bib20","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.2174\/1568026614666140929124445","article-title":"Structure-based virtual screening for drug discovery: principles, applications and recent advances","volume":"14","author":"Lionta","year":"2014","journal-title":"Curr. Top. Med. Chem."},{"issue":"5","key":"10.1016\/j.jmgm.2026.109578_bib21","doi-asserted-by":"crossref","first-page":"646","DOI":"10.3390\/ph15050646","article-title":"Drug design by pharmacophore and virtual screening approach","volume":"15","author":"Giordano","year":"2022","journal-title":"Pharmaceuticals"},{"issue":"4","key":"10.1016\/j.jmgm.2026.109578_bib22","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1002\/bab.2716","article-title":"Dual targeting of MEK1 and Akt kinase identified SBL\u2010027 as a promising lead candidate to control cell proliferations in gastric cancer","volume":"72","author":"Alghamdi","year":"2025","journal-title":"Biotechnol. Appl. Biochem."},{"issue":"26","key":"10.1016\/j.jmgm.2026.109578_bib23","doi-asserted-by":"crossref","DOI":"10.18632\/oncotarget.9153","article-title":"Efficacy of the combination of MEK and CDK4\/6 inhibitors in vitro and in vivo in KRAS mutant colorectal cancer models","volume":"7","author":"Lee","year":"2016","journal-title":"Oncotarget"},{"issue":"8","key":"10.1016\/j.jmgm.2026.109578_bib24","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0044146","article-title":"K-RAS mutant pancreatic tumors show higher sensitivity to MEK than to PI3K inhibition in vivo","volume":"7","author":"Hofmann","year":"2012","journal-title":"PLoS One"},{"issue":"10","key":"10.1016\/j.jmgm.2026.109578_bib25","doi-asserted-by":"crossref","first-page":"4286","DOI":"10.1158\/0008-5472.CAN-08-4765","article-title":"PI3K pathway activation mediates resistance to MEK inhibitors in KRAS mutant cancers","volume":"69","author":"Wee","year":"2009","journal-title":"Cancer Res."},{"issue":"1","key":"10.1016\/j.jmgm.2026.109578_bib26","article-title":"Ligand based pharmacophore modeling and virtual screening studies to design novel HDAC2 inhibitors","volume":"2014","author":"Kandakatla","year":"2014","journal-title":"Adv. Bioinf."},{"key":"10.1016\/j.jmgm.2026.109578_bib27","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.biopha.2016.11.076","article-title":"Novel butyrylcholinesterase inhibitors through pharmacophore modeling, virtual screening and DFT-based approaches along-with design of bioisosterism-based analogues","volume":"85","author":"Gogoi","year":"2017","journal-title":"Biomed. Pharmacother."},{"issue":"5","key":"10.1016\/j.jmgm.2026.109578_bib28","doi-asserted-by":"crossref","first-page":"3346","DOI":"10.1039\/D3RA08618F","article-title":"Ligand based pharmacophore modelling and integrated computational approaches in the quest for small molecule inhibitors against hCA IX","volume":"14","author":"Saravanan","year":"2024","journal-title":"RSC Adv."},{"issue":"1","key":"10.1016\/j.jmgm.2026.109578_bib29","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/slct.201702392","article-title":"Virtual screening, molecular docking, and DFT studies of some thiazolidine\u20102, 4\u2010diones as potential PIM\u20101 kinase inhibitors","volume":"3","author":"Asati","year":"2018","journal-title":"ChemistrySelect"},{"issue":"10","key":"10.1016\/j.jmgm.2026.109578_bib30","doi-asserted-by":"crossref","first-page":"5321","DOI":"10.1080\/07391102.2023.2226723","article-title":"Field-based 3D-QSAR for tyrosine protein kinase JAK-2 inhibitors","volume":"42","author":"Andole","year":"2024","journal-title":"J. Biomol. Struct. Dyn."},{"issue":"1","key":"10.1016\/j.jmgm.2026.109578_bib31","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s40203-023-00142-8","article-title":"Computational design, molecular properties, ADME, and toxicological analysis of substituted 2,6-diarylidene cyclohexanone analogs as potent pyridoxal kinase inhibitors","volume":"11","author":"Ugbe","year":"2023","journal-title":"Silico Pharmacol."},{"issue":"8","key":"10.1016\/j.jmgm.2026.109578_bib32","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s12032-021-01513-x","article-title":"Computational study on novel natural inhibitors targeting BCL2","volume":"38","author":"Lv","year":"2021","journal-title":"Med. Oncol."},{"key":"10.1016\/j.jmgm.2026.109578_bib33","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.molstruc.2016.12.006","article-title":"3D-QSAR and virtual screening studies of thiazolidine-2, 4-dione analogs: validation of experimental inhibitory potencies towards PIM-1 kinase","volume":"1133","author":"Asati","year":"2017","journal-title":"J. Mol. Struct."},{"key":"10.1016\/j.jmgm.2026.109578_bib34","author":"Bhardwaj"},{"key":"10.1016\/j.jmgm.2026.109578_bib35","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiolchem.2024.108049","article-title":"In silico exploration of CB2 receptor agonist in the management of neuroinflammatory conditions by pharmacophore modeling","volume":"110","author":"Bodke","year":"2024","journal-title":"Comput. Biol. Chem."},{"issue":"6","key":"10.1016\/j.jmgm.2026.109578_bib36","doi-asserted-by":"crossref","first-page":"4017","DOI":"10.1007\/s11030-023-10792-7","article-title":"Sulfonamido, amido heterocyclic adducts of tetrazole derivatives as BACE1 inhibitors: in silico exploration","volume":"28","author":"Joshi","year":"2024","journal-title":"Mol. Divers."},{"key":"10.1016\/j.jmgm.2026.109578_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.115908","article-title":"Bisbenzylisoquinoline alkaloid fangchinoline derivative HY-2 inhibits breast cancer cells by suppressing BLM DNA helicase","volume":"169","author":"Zhang","year":"2023","journal-title":"Biomed. Pharmacother."}],"container-title":["Journal of Molecular Graphics and Modelling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1093326326003049?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1093326326003049?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:52:54Z","timestamp":1791859974000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1093326326003049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":37,"alternative-id":["S1093326326003049"],"URL":"https:\/\/doi.org\/10.1016\/j.jmgm.2026.109578","relation":{},"ISSN":["1093-3263"],"issn-type":[{"value":"1093-3263","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Ligand-based pharmacophore modeling and molecular dynamics driven discovery of novel MEK1 inhibitors targeting KRAS signalling pathway","name":"articletitle","label":"Article Title"},{"value":"Journal of Molecular Graphics and Modelling","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jmgm.2026.109578","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"109578"}}