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This study aimed to evaluate synthetic acrylamide quinoxaline derivatives against NSCLC cell lines with different overexpressed EGFR mutations and compare their DMPK profile. The biological activity of LASSBio\u20101971 and LASSBio\u20101974 was assessed through cytotoxicity (MTT and Sulforhodamine B assays), apoptosis induction, EGFR inhibition, cell cycle analysis (flow cytometry), immunofluorescence microscopy, cell membrane permeability (PAMPA assay), and metabolic stability in rat liver microsomes. LASSBio\u20101971 exhibited promising EGFR inhibition with favorable in vitro pharmacokinetic (PK) properties, including high gastrointestinal and blood\u2013brain barrier permeability. LASSBio\u20101974 demonstrated nonselective mechanism inhibiting EGFR and mitotic machinery leading to apoptosis and cell cycle arrest at different phases. LASSBio\u20101971 and LASSBio\u20101974 emerge as EGFR inhibitors with equipotent cytotoxic effects on human NSCLC lines and different in PK profile. Further studies should be conducted with LASSBio\u20101974 to prove and understand its antimicrotubule action.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70151","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T14:21:47Z","timestamp":1763734907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation on LASSBio\u20101971 and LASSBio\u20101974 Cellular Cytotoxic Mechanism and Their Comparative DMPK Profile"],"prefix":"10.1002","volume":"358","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6354-1064","authenticated-orcid":false,"given":"Manoel Oliveira","family":"de Moraes Junior","sequence":"first","affiliation":[{"name":"National Institute of Science and Technology of Pharmaceuticals and Medications (INCT\u2010INOFAR) Federal University of Rio de Janeiro, Laboratory of Evaluation and Synthesis of Bioactive Substances (LASSBio), CCS, University City Rio de 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