Jingjing Jiang, Lingyan Jiang, Benjamin J Maldonato, Yingyun Wang, Matthew Holderfield, Ida Aronchik, Ian P Winters, Zeena Salman, Cristina Blaj, Marie Menard, Jens Brodbeck, Zhe Chen, Xing Wei, Michael J Rosen, Yevgeniy Gindin, Bianca J Lee, James W Evans, Stephanie Chang, Zhican Wang, Kyle J Seamon, Dylan Parsons, James Cregg, Abby Marquez, Aidan C A Tomlinson, Jason K Yano, John E Knox, Elsa Quintana, Andrew J Aguirre, Kathryn C Arbour, Abby Reed, W Clay Gustafson, Adrian L Gill, Elena S Koltun, David Wildes, Jacqueline A M Smith, Zhengping Wang, Mallika Singh
UNLABELLED: RAS-driven cancers comprise up to 30% of human cancers. RMC-6236 is a RAS(ON) multi-selective noncovalent inhibitor of the active, GTP-bound state of both mutant and wild-type variants of canonical RAS isoforms with broad therapeutic potential for the aforementioned unmet medical need. RMC-6236 exhibited potent anticancer activity across RAS-addicted cell lines, particularly those harboring mutations at codon 12 of KRAS. Notably, oral administration of RMC-6236 was tolerated in vivo and drove profound tumor regressions across multiple tumor types in a mouse clinical trial with KRASG12X xenograft models...
April 9, 2024: Cancer Discovery