Supplementary Figures 1 - 11 from AG-221, a First-in-Class Therapy Targeting Acute Myeloid Leukemia Harboring Oncogenic <i>IDH2</i> Mutations

Supplementary Figure 1. Synthesis and pharmacokinetic characterization of AG-221. Supplementary Figure 2. Biochemical attributes of AG-221. Supplementary Figure 3. Biochemistry of AG-221 with respect to substrate and cofactor. Supplementary Figure 4. TF-1 IDH2R140Q cells treated with AG-221. Supplementary Figure 5. AG-221 can reverse the block in EPO-induced differentiation caused by the expression of IDH2R140Q in the TF-1 erythroleukemia cell line. Supplementary Figure 6. Pharmacokinetics/pharmacodynamics of AG-221 in IDH2R140Qmutant U87MG xenograft tumor-bearing mice. Supplementary Figure 7. AG-221 does not affect intrinsic hematological parameters or body weight. Supplementary Figure 8. AG-221 strongly reduces the number of human IDH2R140Q blasts in the liver and spleen in AML-1, AML-2, and AML-3. Supplementary Figure 9. Flow cytometry analyses of bone marrow-derived hCD45+ cells in primary human AML xenograft models. Supplementary Figure 10. Affinity of the IDH2R140Q homodimer for NADPH. Supplementary Figure 11. Electron density map diagrams for bound ligands for IDH2R140Q co-complex structures determined by X-ray crystallography.