To verify the in vitro results in a cellular system, we measured the relative levels of active GTP-bound KRAS(WT) and KRAS(G12C) and performed cell viability assays with wild-type KRAS, HRAS, and NRAS (Figure , and S5). RAS-GTP levels were measured after the cells were starved in the presence of adagrasib and sotorasib, followed by mitogenic stimulation with 10% fetal calf serum (FCS). This condition was selected to mimic the nucleotide exchange assays in cellulo. Both adagrasib and sotorasib demonstrated comparable inhibition of KRAS(G12C) activation at the expected concentrations (Table ). Next, we confirmed the cross-reactivity of adagrasib on KRAS(WT) at micromolar concentrations (>1 µM), while sotorasib did not show any effect at the tested concentrations (Figure ). On the other hand, adagrasib started to exhibit KRAS-independent toxicity already at low micromolar concentrations (Figure ). Toxicity was also observed in the cell viability assays using Ba/F3 cells stably expressing human KRAS(G12C) or wild-type KRAS, NRAS, and HRAS. In KRAS(G12C) expressing cells, both compounds inhibited viability at low nanomolar concentrations (Table ). In contrast, in the case of K/N/HRAS(WT) expressing cells, only a minor effect on cell viability was observed with sotorasib (Figure and Table ).