Development of Highly Potent and Selective FGFR4 Inhibitors Based on SNAr Electrophiles
Moritz Schwarz,
Maksym Kurkunov,
Florian Wittlinger
et al.
Abstract:Fibroblast Growth Factor Receptor 4 (FGFR4) is thought to be a driver in several cancer types, most notably in hepatocellular carcinoma. One way to achieve high potency and isoform-selectivity for FGFR4 is to covalently target a rare cysteine (C552) in the hinge region of its kinase domain that is not present in other FGFR family members (FGFR1-3). Typically, this cysteine is addressed via classical acrylamide electrophiles. Here, we demonstrate that non-canonical covalent “warheads” based on nucleophilic arom… Show more
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