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. Author manuscript; available in PMC: 2022 Dec 20.
Published in final edited form as: Nat Cancer. 2022 Jun 20;3(6):710–722. doi: 10.1038/s43018-022-00399-6

Fig. 6. Cellular IC50 changes with single and compound ALK mutations.

Fig. 6.

(A)-(B) Comparison of absolute and fold shift in cellular IC50 values for nonmutant, single and compound ALK mutants (corresponding to data shown in Extended Data Fig. 9A). G1202R (A) and I1171N (B) single point mutations result in large shift in IC50 for lorlatinib; however, this remains within range of clinical exposure (<200nM, indicated by dashed line). Compound mutations result in comparable fold shift in IC50 values of lorlatinib, LA7 and LA9 relative to single mutations; however, the improved potency of LA7 and LA9 against single mutations results in substantial improvement in IC50 against compound mutations. (C)-(D) Fold improvement of LA7 (C) or LA9 (D) compared to lorlatinib against single and compound mutations (calculated by dividing the lorlatinib IC50 by the LA IC50, corresponding to data shown in Extended Data Fig. 9B).