Supplementary Materials

The PDF file includes:

  • Materials and Methods
  • Fig. S1. AZD3229 inhibits KIT exon 9 insertion more potently than ripretinib and avapritinib.
  • Fig. S2. AZD3229 is more potent than ripretinib and avapritinib in inhibiting KIT exon 11 deletion mutation.
  • Fig. S3. Plasma PK of AZD3229 in mice.
  • Fig. S4. AZD3229 PD analysis in KIT exon 11 deletion PDX model.
  • Fig. S5. Comparison of AZD3229, ripretinib, and avapritinib in inhibiting KIT exon 11 deletion/V654A in GIST430/654 cells.
  • Fig. S6. Induction of apoptosis by AZD3229 in GIST430/654 cells.
  • Fig. S7. Time- and dose-dependent inhibition of KIT signaling by AZD3229 in GIST430/654 cells.
  • Fig. S8. AZD3229 dosing in a GIST430/654 model does not alter body weight in mice.
  • Fig. S9. AZD3229 PD analysis in a GIST430/654 model.
  • Fig. S10. Plasma concentrations of AZD3229 correlate with inhibition of KIT signaling by AZD3229 in a GIST430/654 model.
  • Fig. S11. AZD3229 dosing decreases proliferating cells in GIST430/654 tumors.
  • Fig. S12. KIT exon 11 deletion/V654A PDX model is resistant to imatinib.
  • Fig. S13. AZD3229, imatinib, and sunitinib are well tolerated in SCID mice bearing Ba/F3 KIT exon 11 deletion/D816H tumors.
  • Fig. S14. AZD3229 dosing in KIT K642E/N822K PDX model is well tolerated.
  • Fig. S15. AZD3229 PD analysis in KIT A-loop PDX model (KIT K642E/N822K).
  • Fig. S16. AZD3229 PD analysis in KIT A-loop PDX model (KIT exon 11 deletion/Y823D).
  • Table S1. Biochemical enzyme profiling of AZD3229 across the Thermo Fisher Scientific kinome panel.

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