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Your search keyword '"Arz, Dorothee"' showing total 7 results
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7 results on '"Arz, Dorothee"'

1. JDQ443, a Structurally Novel, Pyrazole-Based, Covalent Inhibitor of KRASG12C for the Treatment of Solid Tumors

Author

Lorthiois, Edwige, primary, Gerspacher, Marc, additional, Beyer, Kim S., additional, Vaupel, Andrea, additional, Leblanc, Catherine, additional, Stringer, Rowan, additional, Weiss, Andreas, additional, Wilcken, Rainer, additional, Guthy, Daniel A., additional, Lingel, Andreas, additional, Bomio-Confaglia, Claudio, additional, Machauer, Rainer, additional, Rigollier, Pascal, additional, Ottl, Johannes, additional, Arz, Dorothee, additional, Bernet, Pascal, additional, Desjonqueres, Gaëlle, additional, Dussauge, Solene, additional, Kazic-Legueux, Malika, additional, Lozac’h, Marie-Anne, additional, Mura, Christophe, additional, Sorge, Mickaël, additional, Todorov, Milen, additional, Warin, Nicolas, additional, Zink, Florence, additional, Voshol, Hans, additional, Zecri, Frederic J., additional, Sedrani, Richard C., additional, Ostermann, Nils, additional, Brachmann, Saskia M., additional, and Cotesta, Simona, additional

Published
2022
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2. JDQ443, a Structurally Novel, Pyrazole-Based, Covalent Inhibitor of KRASG12C for the Treatment of Solid Tumors.

Author

Lorthiois, Edwige, Gerspacher, Marc, Beyer, Kim S., Vaupel, Andrea, Leblanc, Catherine, Stringer, Rowan, Weiss, Andreas, Wilcken, Rainer, Guthy, Daniel A., Lingel, Andreas, Bomio-Confaglia, Claudio, Machauer, Rainer, Rigollier, Pascal, Ottl, Johannes, Arz, Dorothee, Bernet, Pascal, Desjonqueres, Gaëlle, Dussauge, Solene, Kazic-Legueux, Malika, and Lozac'h, Marie-Anne

Published
2022
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3. JDQ443, a Structurally Novel, Pyrazole-Based, Covalent Inhibitor of KRASG12Cfor the Treatment of Solid Tumors

Author

Lorthiois, Edwige, Gerspacher, Marc, Beyer, Kim S., Vaupel, Andrea, Leblanc, Catherine, Stringer, Rowan, Weiss, Andreas, Wilcken, Rainer, Guthy, Daniel A., Lingel, Andreas, Bomio-Confaglia, Claudio, Machauer, Rainer, Rigollier, Pascal, Ottl, Johannes, Arz, Dorothee, Bernet, Pascal, Desjonqueres, Gaëlle, Dussauge, Solene, Kazic-Legueux, Malika, Lozac’h, Marie-Anne, Mura, Christophe, Sorge, Mickaël, Todorov, Milen, Warin, Nicolas, Zink, Florence, Voshol, Hans, Zecri, Frederic J., Sedrani, Richard C., Ostermann, Nils, Brachmann, Saskia M., and Cotesta, Simona

Abstract

Rapid emergence of tumor resistance via RAS pathway reactivation has been reported from clinical studies of covalent KRASG12Cinhibitors. Thus, inhibitors with broad potential for combination treatment and distinct binding modes to overcome resistance mutations may prove beneficial. JDQ443 is an investigational covalent KRASG12Cinhibitor derived from structure-based drug design followed by extensive optimization of two dissimilar prototypes. JDQ443 is a stable atropisomer containing a unique 5-methylpyrazole core and a spiro-azetidine linker designed to position the electrophilic acrylamide for optimal engagement with KRASG12CC12. A substituted indazole at pyrazole position 3 results in novel interactions with the binding pocket that do not involve residue H95. JDQ443 showed PK/PD activity in vivo and dose-dependent antitumor activity in mouse xenograft models. JDQ443 is now in clinical development, with encouraging early phase data reported from an ongoing Phase Ib/II clinical trial (NCT04699188).

Published
2022
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6. Identification and optimisation of 4,5-dihydrobenzo[1,2-d:3,4-d]bisthiazole and 4,5-dihydrothiazolo[4,5-h]quinazoline series of selective phosphatidylinositol-3 kinase alpha inhibitors

Author

Fairhurst, Robin A., Gerspacher, Marc, Imbach-Weese, Patricia, Mah, Robert, Caravatti, Giorgio, Furet, Pascal, Fritsch, Christine, Schnell, Christian, Blanz, Joachim, Blasco, Francesca, Desrayaud, Sandrine, Guthy, Daniel A., Knapp, Mark, Arz, Dorothee, Wirth, Jasmin, Roehn-Carnemolla, Esther, and Luu, Van Huy

Published
2015
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7. JDQ443, a Structurally Novel, Pyrazole-Based, Covalent Inhibitor of KRAS G12C for the Treatment of Solid Tumors.

Author

Lorthiois E, Gerspacher M, Beyer KS, Vaupel A, Leblanc C, Stringer R, Weiss A, Wilcken R, Guthy DA, Lingel A, Bomio-Confaglia C, Machauer R, Rigollier P, Ottl J, Arz D, Bernet P, Desjonqueres G, Dussauge S, Kazic-Legueux M, Lozac'h MA, Mura C, Sorge M, Todorov M, Warin N, Zink F, Voshol H, Zecri FJ, Sedrani RC, Ostermann N, Brachmann SM, and Cotesta S

Subjects
Animals, Humans, Mice, Disease Models, Animal, Drug Design, Mutation, Pyrazoles pharmacology, Pyrazoles therapeutic use, Neoplasms drug therapy, Neoplasms genetics, Proto-Oncogene Proteins p21(ras)
Abstract

Rapid emergence of tumor resistance via RAS pathway reactivation has been reported from clinical studies of covalent KRAS G12C inhibitors. Thus, inhibitors with broad potential for combination treatment and distinct binding modes to overcome resistance mutations may prove beneficial. JDQ443 is an investigational covalent KRAS G12C inhibitor derived from structure-based drug design followed by extensive optimization of two dissimilar prototypes. JDQ443 is a stable atropisomer containing a unique 5-methylpyrazole core and a spiro-azetidine linker designed to position the electrophilic acrylamide for optimal engagement with KRAS G12C C12. A substituted indazole at pyrazole position 3 results in novel interactions with the binding pocket that do not involve residue H95. JDQ443 showed PK/PD activity in vivo and dose-dependent antitumor activity in mouse xenograft models. JDQ443 is now in clinical development, with encouraging early phase data reported from an ongoing Phase Ib/II clinical trial (NCT04699188).

Published
2022
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