Combined KRAS G12C and SOS1 inhibition enhances and extends the anti-tumor response in KRAS G12C -driven cancers by addressing intrinsic and acquired resistance.
Biorxiv : The Preprint Server For Biology
Thatikonda, Venu V; Lu, Hengyu H; Jurado, Sabine S; Kostyrko, Kaja K; Bristow, Christopher A CA; Bosch, Karin K; Feng, Ningping N; Gao, Sisi S; Gerlach, Daniel D; Gmachl, Michael M; Lieb, Simone S; Jeschko, Astrid A; Machado, Annette A AA; Marszalek, Ethan D ED; Mahendra, Mikhila M; Jaeger, Philipp A PA; Sorokin, Alexey A; Strauss, Sandra S; Trapani, Francesca F; Kopetz, Scott S; Vellano, Christopher P CP; Petronczki, Mark M; Kraut, Norbert N; Heffernan, Timothy P TP; Marszalek, Joseph R JR; Pearson, Mark M; Waizenegger, Irene I; Hofmann, Marco H MH
Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, and Selective Covalent Oral Inhibitor of KRASG12C.
Cancer Discovery
Weiss, Andreas A; Lorthiois, Edwige E; Barys, Louise L; Beyer, Kim S KS; Bomio-Confaglia, Claudio C; Burks, Heather H; Chen, Xueying X; Cui, Xiaoming X; de Kanter, Ruben R; Dharmarajan, Lekshmi L; Fedele, Carmine C; Gerspacher, Marc M; Guthy, Daniel Alexander DA; Head, Victoria V; Jaeger, Ashley A; Núñez, Eloísa Jiménez EJ; Kearns, Jeffrey D JD; Leblanc, Catherine C; Maira, Sauveur-Michel SM; Murphy, Jason J; Oakman, Helen H; Ostermann, Nils N; Ottl, Johannes J; Rigollier, Pascal P; Roman, Danielle D; Schnell, Christian C; Sedrani, Richard R; Shimizu, Toshio T; Stringer, Rowan R; Vaupel, Andrea A; Voshol, Hans H; Wessels, Peter P; Widmer, Toni T; Wilcken, Rainer R; Xu, Kun K; Zecri, Frederic F; Farago, Anna F AF; Cotesta, Simona S; Brachmann, Saskia M SM
RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site.
Nature Communications
Haza, Katarzyna Z KZ; Martin, Heather L HL; Rao, Ajinkya A; Turner, Amy L AL; Saunders, Sophie E SE; Petersen, Britta B; Tiede, Christian C; Tipping, Kevin K; Tang, Anna A AA; Ajayi, Modupe M; Taylor, Thomas T; Harvey, Maia M; Fishwick, Keri M KM; Adams, Thomas L TL; Gaule, Thembaninkosi G TG; Trinh, Chi H CH; Johnson, Matthew M; Breeze, Alexander L AL; Edwards, Thomas A TA; McPherson, Michael J MJ; Tomlinson, Darren C DC
Exquisitely Specific anti-KRAS Biodegraders Inform on the Cellular Prevalence of Nucleotide-Loaded States.
Acs Central Science
Lim, Shuhui S; Khoo, Regina R; Juang, Yu-Chi YC; Gopal, Pooja P; Zhang, Huibin H; Yeo, Constance C; Peh, Khong Ming KM; Teo, Jinkai J; Ng, Simon S; Henry, Brian B; Partridge, Anthony W AW
KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe.
Nature Communications
Bery, Nicolas N; Legg, Sandrine S; Debreczeni, Judit J; Breed, Jason J; Embrey, Kevin K; Stubbs, Christopher C; Kolasinska-Zwierz, Paulina P; Barrett, Nathalie N; Marwood, Rose R; Watson, Jo J; Tart, Jon J; Overman, Ross R; Miller, Ami A; Phillips, Christopher C; Minter, Ralph R; Rabbitts, Terence H TH