{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["65(14)"],"submitter":["Eno MS"],"pubmed_abstract":["While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment landscape for EGFR mutant (L858R and ex19del)-driven non-small-cell lung cancer (NSCLC), most patients will eventually develop resistance to TKIs. In the case of first- and second-generation TKIs, up to 60% of patients will develop an EGFR T790M mutation, while third-generation irreversible TKIs, like osimertinib, lead to C797S as the primary on-target resistance mutation. The development of reversible inhibitors of these resistance mutants is often hampered by poor selectivity against wild-type EGFR, resulting in potentially dose-limiting toxicities and a sub-optimal profile for use in combinations. BLU-945 (compound <b>30</b>) is a potent, reversible, wild-type-sparing inhibitor of "],"journal":["Journal of medicinal chemistry"],"pagination":["9662-9677"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9340769"],"repository":["biostudies-literature"],"pubmed_title":["Discovery of BLU-945, a Reversible, Potent, and Wild-Type-Sparing Next-Generation EGFR Mutant Inhibitor for Treatment-Resistant Non-Small-Cell Lung Cancer."],"pmcid":["PMC9340769"],"pubmed_authors":["Campbell JE","Timsit Y","Wilson K","Kim J","Guzi TJ","Lee C","Schalm S","Singh J","De Savi C","Brooijmans N","Stevison F","Hsieh J","Ozen A","Perola E","Williams BD","Fetalvero K","Kinkema C","Garner A","Wilson D","Albayya F","Zhang Z","Zalutskaya A","Medendorp C","Dineen TA","Brown V","Brubaker JD","Eno MS","Woessner R"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of BLU-945, a Reversible, Potent, and Wild-Type-Sparing Next-Generation EGFR Mutant Inhibitor for Treatment-Resistant Non-Small-Cell Lung Cancer.","description":"While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment landscape for EGFR mutant (L858R and ex19del)-driven non-small-cell lung cancer (NSCLC), most patients will eventually develop resistance to TKIs. In the case of first- and second-generation TKIs, up to 60% of patients will develop an EGFR T790M mutation, while third-generation irreversible TKIs, like osimertinib, lead to C797S as the primary on-target resistance mutation. The development of reversible inhibitors of these resistance mutants is often hampered by poor selectivity against wild-type EGFR, resulting in potentially dose-limiting toxicities and a sub-optimal profile for use in combinations. BLU-945 (compound <b>30</b>) is a potent, reversible, wild-type-sparing inhibitor of ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2026-05-09T15:35:49.544Z","creation":"2025-04-06T09:22:25.313Z"},"accession":"S-EPMC9340769","cross_references":{"pubmed":["35838760"],"doi":["10.1021/acs.jmedchem.2c00704"]}}