Supplementary Materials

The PDF file includes:

  • Materials and Methods
  • Fig. S1. FLT3+ AML develop adaptive resistance to FLT3i.
  • Fig. S2. Adaptively resistant FLT3+ AML exhibit increased IRAK1/4 activation.
  • Fig. S3. Quizartinib induces TLR9-mediated activation of IRAK4.
  • Fig. S4. Inhibition of IRAK1/4 sensitizes FLT3+ AML to quizartinib.
  • Fig. S5. NCGC1481 exhibits promising physicochemical and in vivo pharmacokinetic properties.
  • Fig. S6. 2D interaction diagrams for NCGC1481 bound to FLT3 and IRAK4.
  • Fig. S7. NCGC1481 inhibits compensatory IRAK1/4 activation and adaptive resistance of FLT3-ITD AML.
  • Fig. S8. NCGC1481 prevents adaptive resistance of FLT3-ITD AML cells in vitro and has minimal effects on normal hematopoietic cells.
  • Fig. S9. NCGC1481 reduces the leukemic burden of FLT3-ITD AML.
  • Fig. S10. NCGC1481 reduces the leukemic burden of FLT3-ITD AML after quizartinib treatment.
  • References (9397)

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Other Supplementary Material for this manuscript includes the following:

  • Data file S1 (Microsoft Excel format) contains the following tables:
  • Table S1. Peptide phosphorylation in the PamChip serine-threonine in-cell kinase array.
  • Table S2. Top active kinases inferred from the PamChip in-cell kinase assay.
  • Table S3. Gene expression analysis of FLT3-ITD AML treated with FLT3i.
  • Table S4. AML patients evaluated with gilteritinib.
  • Table S5. Reaction Biology profile of NCGC1481.
  • Table S6. KiNativ profile of NCGC1481 in MV4;11 lysate.
  • Table S7. Characteristics of patients with AML.
  • Table S8. Peptide phosphorylation in the PamChip serine-threonine in-cell kinase array with NCGC1481 treatment.
  • Table S9. Gene expression analysis of FLT3-ITD AML treated with NCGC1481.
  • Data file S2 (Microsoft Excel format). Original data.