Blood, Vol. 112, Issue 13, 5161-5170, December 15, 2008

Antileukemic effects of the novel, mutant FLT3 inhibitor NVP-AST487: effects on PKC412-sensitive and -resistant FLT3-expressing cells
Blood Weisberg et al. 112: 5161

Supplemental materials for: Weisberg et al

Files in this Data Supplement:

• Table S1. AML patient data (PDF, 13.6 KB)
  
  
• Table S2. Determination of Ki for NVP-AST487 (PDF, 34.9 KB)
  
  
• Table S3. Spleen weights of vehicle- and NVP-AST487–treated athymic nude mice (PDF, 12.7 KB)
  
  
• Figure S1. Three-day treatment of FLT3-N841I-Ba/F3 cells, in the presence and absence of IL-3, with NVP-AST487 (JPG, 43.6 KB) -
  
  
  
  
  
  
• Figure S2. NVP-AST487: Ki determination for Flt3 (JPG, 126 KB) -
  
  
  
  
  
  
• Figure S3. Efficacy of NVP-AST487 (“AST487”) against FLT3-ITD-Ba/F3 cells cultured for 66 hours in presence of 10% fetal calf serum versus 10% human serum (n=2, fetal calf serum; n=1, human serum) (JPG, 27.4 KB) -
  
  
  
  
  
  
• Figure S4. Proliferation study investigating the effect of NVP-AST487 (“AST487”) combined with Ara-C against FLT3-ITD-Ba/F3 cells (JPG, 44.7 KB) -
  Calcusyn analysis of the combination of Ara-C and NVP-AST487 suggested effects that ranged from nearly additive to moderately synergistic (ED25: 1.06961; ED50: 0.97327; ED75: 0.88947; ED90: 0.81665).
  
  
  
  
  
  
• Figure S5. Treatment of Ba/F3-FLT3/ITD-luc⁺ cells (JPG, 139 KB) -
  (A) Treatment of Ba/F3-FLT3-ITD-luc⁺ cells using sequential administration of Ara-c and NVP-AST487. (B) Treatment of Ba/F3-FLT3-ITD-luc⁺ cells using sequential administration of Ara-c and NVP-AST487. (C) Treatment of Ba/F3-FLT3-ITD-luc⁺ cells using sequential administration of NVP-AST487 and Ara-c. (D) Treatment of Ba/F3-FLT3-ITD-luc⁺ cells using sequential administration of NVP-AST487 and Ara-c. (E) Treatment of Ba/F3-FLT3-ITD-luc⁺ cells using simultaneous administration of NVP-AST487 and Ara-c. (F) Treatment of Ba/F3-FLT3-ITD-luc⁺ cells using simultaneous administration of NVP-AST487 and Ara-c.
  
  
  
  
  
  
• Figure S6. Treatment of Ba/F3-FLT3-ITD-luc⁺ cells (JPG, 145 KB) -
  (A) Treatment of Ba/F3-FLT3-ITD-luc⁺ cells using sequential administration of doxorubicin and NVP-AST487. (B) Treatment of Ba/F3-FLT3-ITD-luc⁺ cells using sequential administration of doxorubicin and NVP-AST487. (C) Treatment of Ba/F3-FLT3-ITD-luc⁺ cells using sequential administration of NVP-AST487 and doxorubicin. (D) Treatment of Ba/F3-FLT3-ITD-luc⁺ cells using sequential administration of NVP-AST487 and doxorubicin. (E) Treatment of Ba/F3-FLT3-ITD-luc⁺ cells using simultaneous administration of NVP-AST487 and doxorubicin. (F) Treatment of Ba/F3-FLT3-ITD-luc⁺ cells using simultaneous administration of NVP-AST487 and doxorubicin.
  
  
  
  
  
  
• Figure S7. Structural model: a model of NVP-AST487 bound to the FLT3 kinase domain (JPG, 54 KB) -