AstraZeneca's "compound 28" and AZD4625 (PDB IDs: 7OO7, 7O70) that share partially analogous 8-membered ether ring structure with LY3537982 (Figure ), do display interaction to Lys16 in their crystal structures. The lack of this interaction could potentially be a simulation artefact that is caused by the starting configuration based on BI-0474 (PDB: 8AFB) (Figures and), which does not display interaction to Lys16. On the other hand, a similar fused-thiophene headgroup to what is present in LY3537982 is present in this location with the non-covalent pan-KRAS inhibitors recently disclosed by Boehringer-Ingelheim, which are not dependent on Lys16 interactions . Therefore, we speculate that the observed strong binding of LY3537982 may be driven by the Met72 pocket that could simultaneously also allow less dependency on the Lys16 side.