Fig. 9: Possible mechanisms of IDH1 R132Q selective mutant IDH1 inhibitor resistance. | Nature Communications

Fig. 9: Possible mechanisms of IDH1 R132Q selective mutant IDH1 inhibitor resistance.

From: Active site remodeling in tumor-relevant IDH1 mutants drives distinct kinetic features and potential resistance mechanisms

Fig. 9

We have reported previously that IDH1 R132Q binds selective mutant IDH1 inhibitors poorly. A A previously solved structure of a selective IDH1 R132H inhibitor (6O2Y)40 was aligned to WT13, R132H30, and R132Q binary complexes. In (B–E), residues A111-V121 are shown as a surface. B The structure of the inhibitor bound to a R132H:NADP(H) complex40. Residues A111-V121 in R132Q:NADP(H) (C) and in WT:NADP(H) (D) obstruct the inhibitor binding pocket. E The inhibitor could be accommodated in the structure of R132H:NADP(H)30.

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