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Our covalent heterocyclic fragment library (Covalent MiniFrags) consisting of five and six membered heterocycles was screened against the oncogenic target KRas\n                    <jats:sup>G12C<\/jats:sup>\n                    . First, we detected the labeling of cysteine residues by Ellman's free thiol assay. Primary hits were characterized in a GSH reactivity assay and next we confirmed covalent labeling by RapidFire MS. Fragment hits with the best potential and selectivity were combined in silico with the quinazoline core of ARS\u20101620, and the best candidate was chosen for synthesis. Binding of the heterocyclic ARS derivative was confirmed via intact MS and HSQC NMR measurements. Its functional activity was characterized by nucleotide exchange assay and cell viability assay on cell lines expressing KRas\n                    <jats:sup>G12C<\/jats:sup>\n                    . Our results support that screening of the heterocyclic electrophilic fragment library could provide viable chemical starting points for the development of targeted covalent inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70342","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:55:22Z","timestamp":1790060122000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fragment\u2010Based Screening of Heterocyclic Electrophiles Identified Acrylamide Bioisoteres for Covalent KRas\n                    <sup>G12C<\/sup>\n                    Inhibitors"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8902-7206","authenticated-orcid":false,"given":"Nikolett","family":"P\u00e9czka","sequence":"first","affiliation":[{"name":"Medicinal Chemistry Research Group and National Drug Discovery and Development Laboratory HUN\u2010REN Research Centre 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