Supplementary Figure S1-S6 from Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers
Year: 2024
Type: supplementary-materials
Abstract: Supplementary Figure 1 shows RMC-6236 crystal structure in tri-complex, as well as biophysical and cellular potencies of RMC-6236 by genotype. Supplementary Figure 2 shows RMC-6236 demonstrates dose-dependent anti-tumor activities at tolerable doses; and pharmacodynamic effects on RAS signaling in NCI-H441 xenograft tumors as assessed by IHC, and in relatively refractory KP-4 and NCI-H2122 xenograft tumors as assessed by human DUSP6 mRNA expression in vivo. Supplementary Figure 3 shows genotype dependent response of RMC-6236 across NSCLC, PDAC and CRC; and potential modifiers to the durability of response of KRASG12C NSCLC models upon RMC-6236 treatment assessed by Kaplan-Meier analyses. Supplementary Figure 4 shows Efficacy of RMC-6236 on KrasG12C–driven autochthonous lung tumors harboring cis second-site mutations within KrasG12C (KrasG12C,H95D or KrasG12C,Y96C) and eCT26 (KrasG12D/G12D) syngeneic model in immunocompetent mice; anti-tumor immunity of RMC-6236; and in intracranially implanted NCI-H1373-Luc xenograft model on nude mice. Supplementary Figure 5 shows effects of RMC-6236 mediated pharmacological modulation in KP-4 xenograft tumors and normal colon tissues isolated from xenograft tumor bearing mice. Supplementary Figure 6 shows a graphical representation of the combined mouse PK-Efficacy and PK/PD model.
Authors: 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
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4399329014