Extended Data Fig. 1
From: Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer
(a) Viability levels of human PDAC cell lines (from Fig. 1b) with KRASG12X, KRASQ61H, and BRAFΔV487-P492 mutations treated with indicated concentrations of RMC-7977 for 5 days. Data points represent the mean of biological 3 replicates normalized to DMSO control. KRAS mutations are indicated by curve colors. Error bars indicate ±s.d. (b,c) Viability levels of human PDAC cell lines with (b) KRASQ61H mutation or (c) KRASWT treated with DMSO or indicated concentrations of RMC-7977 for 5 days. Data points represent the mean of 3-4 biological replicates normalized to DMSO control. Error bars indicate ±s.d. (d) Viability levels of human PDAC organoids with KRASWT treated with DMSO or indicated concentrations of RMC-7977 for 6 days. Data points represent the mean of 2 biological replicates normalized to DMSO control. Error bars indicate ±s.d. (e) Western Blots of mouse PDAC cell lines treated with DMSO or range of RMC-7977 concentrations (1-100 nM) for 2 h. Protein levels of phospho-ERKT202/Y204 and total ERK were analyzed. Alpha-(α)-tubulin was used as loading control. (f) Western Blots of human PDAC cell lines treated with DMSO or range of RMC-7977 concentrations (1-100 nM) for 24 h. Protein levels of phospho-ERKT202/Y204, total ERK, phospho-pS6S235/236 total S6, phospho-AktT308 and total Akt were analyzed. Vinculin was used as loading control. (g) Western Blots of AsPC-1 cell line treated with DMSO or RMC-7977 (100 nM) for indicated timepoints. Protein levels of phospho-ERKT202/Y204, total ERK, total PARP and cleaved PARP were analyzed. Vinculin was used as loading control. For cell line information see SI Table 5.