Extended Data Fig. 1: Rational design of a non-covalent pan KRAS inhibitor.
From: Pan-KRAS inhibitor disables oncogenic signalling and tumour growth
a, Isogenic BaF3 cells engineered to express the indicated KRAS variants were treated as shown for 72 h to determine the IC50 (n = 2, mean and each replicate). IL3 stimulation was used to induce oncogene independent growth. The effect of treatment in the absence of IL3 is shown in Fig. 1b. *: endogenous KRAS WT. b,c, Co-crystal structures of precursor 1 (b) or BI-2865 (c) bound to KRAS. d, Space filling models of KRAS variants in an apo- or drug-bound conformation. S: switch; *: active state conformation. e, Superimposition of co-crystal structures of KRAS G12C in complex with the covalent inhibitor sotorasib or the pan KRAS inhibitor BI-2865.
