Article
Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, and Selective Covalent Oral Inhibitor of KRASG12C.
Cancer discovery - 2 Jun 2022
Weiss Andreas, Lorthiois Edwige, Barys Louise, Beyer Kim S, Bomio-Confaglia Claudio, Burks Heather, Chen Xueying, Cui Xiaoming, de Kanter Ruben, Dharmarajan Lekshmi, Fedele Carmine, Gerspacher Marc, Guthy Daniel Alexander, Head Victoria, Jaeger Ashley, Núñez Eloísa Jiménez, Kearns Jeffrey D, Leblanc Catherine, Maira Sauveur-Michel, Murphy Jason, Oakman Helen, Ostermann Nils, Ottl Johannes, Rigollier Pascal, Roman Danielle, Schnell Christian, Sedrani Richard, Shimizu Toshio, Stringer Rowan, Vaupel Andrea, Voshol Hans, Wessels Peter, Widmer Toni, Wilcken Rainer, Xu Kun, Zecri Frederic, Farago Anna F, Cotesta Simona, Brachmann Saskia M
Abstract excerpt
Covalent inhibitors of KRASG12C have shown antitumor activity against advanced/metastatic KRASG12C-mutated cancers, though resistance emerges and additional strategies are needed to improve outcomes. JDQ443 is a structurally unique covalent inhibitor of GDP-bound KRASG12C that forms novel interactions with the switch II pocket. JDQ443 potently inhibits KRASG12C-driven cellular signaling and demonstrates selective...
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