Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a 5-Fluoro-4-(3H)-quinazolinone Aryl Urea pan-RAF Kinase Inhibitor.

doi:10.1021/acs.jmedchem.0c02085

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Article

Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a 5-Fluoro-4-(3H)-quinazolinone Aryl Urea pan-RAF Kinase Inhibitor.

Journal of medicinal chemistry - 8 Apr 2021

Huestis Malcolm P, Dela Cruz Darlene, DiPasquale Antonio G, Durk Matthew R, Eigenbrot Charles, Gibbons Paul, Gobbi Alberto, Hunsaker Thomas L, La Hank, Leung Dennis H, Liu Wendy, Malek Shiva, Merchant Mark, Moffat John G, Muli Christine S, Orr Christine J, Parr Brendan T, Shanahan Frances, Sneeringer Christopher J, Wang Weiru, Yen Ivana, Yin Jianping, Siu Michael, Rudolph Joachim

Abstract excerpt

Optimization of a series of aryl urea RAF inhibitors led to the identification of type II pan-RAF inhibitor GNE-0749 (7), which features a fluoroquinazolinone hinge-binding motif. By minimizing reliance on common polar hinge contacts, this hinge binder allows for a greater contribution of RAF-specific residue interactions, resulting in exquisite kinase selectivity. Strategic substitution of fluorine at the C5...

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PMID: 33780623
DOI: 10.1021/acs.jmedchem.0c02085

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 6 Sept 2026. Manifest publication-graph-cohort-2026-09-06.1.

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