Mutated KRAS is considered one of the key targets in cancer drug discovery. The success of covalent inhibition of KRAS(G12C) to its switch-II pocket (SII-P) (reviewed in ), is exemplified by the first clinically approved KRAS targeting drug sotorasib. This success has fostered the currently ongoing efforts to target the SII-P of other KRAS mutants beyond G12C, including G12D 4 , G12S , and G12R . A number of other approaches towards direct KRAS targeting with small molecules, such as targeting SI/SII (switch-I/switch-II) site, have mainly resulted in lower affinity compounds . Therefore, SII-P appears to offer the most promising approach to tackle this oncoprotein with small-molecule inhibitors that has been reported to date.