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Table 2 Non-linear regression analysis of IC50s (Apoptosis/Viability)

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

  Cell line    Target IC50 (nM)  
   Induction of apoptosis
HMC1.1 KIT V560G 31
HMC1.2 KIT V560G/D816V not reached*
p815 KIT D814Y (murine) 341
Kasumi-1 KIT N822K 67
M-07e + SCF KIT-activated 78
M-07e + GM-CSF unspecific stimulation not reached*
K562 BCR/ABL not reached*
HL60 N/A not reached*
Jurkat N/A not reached*
MV4;11 FLT3 ITD (hemizygous) 2
GIST822 KIT K642E 109
GIST48 KIT V560D/D820A not reached*
Pat.368 FLT3 amplification ? 2998
Pat.601 FLT3 ITD 876
Pat.695, 20% FBS FLT3 ITD 2335
Pat.695, 0.5% FBS FLT3 ITD 25
Pat.139, 20% FBS FLT3 ITD, Relaps 760
Pat.139, 0.5% FBS FLT3 ITD, Relaps 10
   Reduction of viable cells
Pat.507 CBF AML (KIT WT) 1275
Pat.317 CBF AML (KIT D816Y) 1294
Pat.521 CBF AML (KIT WT) 2018
Pat.305 CBF AML (KIT WT) 2954
Pat.511 CBF AML (KIT WT) 4272
Pat.281 CBF AML (KIT WT) 5758
Pat.279 CBF AML (KIT WT) / FLT3 amplification? (subclone) 6607
Pat.523 CBF AML (KIT WT) 7175
Pat.361 CBF AML (KIT D816V) 8443
Pat.239 CBF AML (KIT D816V) not reached*
  1. * tested up to 10 000 nM.
  2. The table summarizes estimated IC50 values obtained by non-linear regression analysis for the cytotoxic activity of quizartinib in leukemia cell lines and primary native leukemia blasts. Native patient blasts were cultured in 20% FBS." to "Cell lines were cultured in 10% FBS; native patient blasts were cultured in 20% FBS. To address methodology aspects towards sensitivity profiles two native FLT3 ITD + patient samples (Pat. 695 with newly diagnosed AML, Pat. 139 with relapsed AML) were co-treated with reduced serum (0.5% FBS).
  3. In addition IC50 estimates for the proapoptotic effect of quizartinib in the imatinib-sensitive GIST solid tumor cell line GIST882, harboring a K642E mutation, and the imatinib-insensitive cell line GIST48, harboring a V560D mutation in addition to a D820A mutation in the tyrosine kinase domain, are provided, revealing sensitivity profiles similar to imatinib.