Skip to main content

Table 3 Estimated IC50s for the proapoptotic and antiproliferative effects of quizartinib in an isogenic cell model of Ba/F3 cells transfected with various mutant TKs

From: Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KIT isoforms

Isoform Mutation locus IC50 (nM) IC50 (nM) IC50 (nM) IC50 (nM)
   Ba/F3 transfectants leukemia cell lines
   Inhibition of proliferation Induction of apotosis Inhibition of proliferation Induction of apotosis
BCR/ABL fusion n.r.* n.r.* not reached (K562) n.r.* (K562)
FLT3 WT N/A 49 11   
FLT3 ITD, 10% FBS juxtamembrane domain 9 5 <1 (MOLM14) 3 (MOLM14)
FLT3 ITD, 0.5%FBS juxtamembrane domain <1 N/D   
FLT3 K663Q tyrosine kinase domain I 14 23   
FLT D835V tyrosine kinase domain II 172 888   
FLT3 D835Y tyrosine kinase domain II 84 24   
KIT WT N/A 474 n.r.* 77 (M0-7e) 210 (MO-7e)
KIT D816F tyrosine kinase domain II 2871 6254   
KIT D816V, 10% FBS tyrosine kinase domain II 3074 8982 1727 (HMC1.2) n.r.* (HMC1.2)
KIT D816V, 0.5% FBS tyrosine kinase domain II 633 N/A   
KIT D816Y, 0.5% FBS tyrosine kinase domain II 366 611 445 (p815) 341 (p815)
parental N/A n.r.* n.r.*   
parental + DMSO N/A n.r.* n.r.*   
  1. *(not reached with tested doses up to 10 000 nM).
  2. Sensitivity of quizartinib is distinct to and differs widely in between different tyrosine kinase isoforms transfected into an isogenic Ba/F3 cellular background. Estimated IC50s were computed using non-linear regression analysis of an average mean of at least 3 experiments for each cell line.
  3. If applicable, IC50s of leukemic cell lines harboring a similar mutation are provided (rows on the right).
  4. Influence of serum-deprivation on sensitivity profiles of quizartinib was tested in two cell strains (Ba/F3 FLT3 ITD or KIT D816V): Cells were cultured in media with a reduced serum concentration (0.5% FBS) and treated with quizartinib the next day.
  5. Solvent-associated non-specific cytotoxicity was excluded using the parental Ba/F3 cell strain treated with DMSO in the highest concentration used for the quizartinib dose experiments.