Extended Data Fig. 3: Orthosteric and allosteric effects determine KRAS selectivity.
From: Pan-KRAS inhibitor disables oncogenic signalling and tumour growth
a, Extracts from RASless MEFs expressing the indicated RAS isoforms were evaluated by immunoblotting. b, HEK293 cells expressing the indicated G12C mutants were treated for 2 h. Cell extracts were subjected to RBD-pull down and immunoblotting to determine the level of active RAS. c,d, Effect of isoform mimetic substitutions on RAS inhibition. HEK293 cells expressing the indicated mutants were treated as shown for 2 h. Cell extracts were subjected to RBD-pull down and immunoblotting to determine the level of active RAS. The effect of H95 mutants is shown in c and the effects of P121, S122, N85 and K117 mutants are shown in c and d. A representative of two independent repeats is shown in a, b, c and d.
