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

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

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*
EOL-1	FIP1L1-PDGFRA	< 1
K562	BCR/ABL	not reached*
HL60	N/A	not reached*
Jurkat	N/A	not reached*
MV4;11	FLT3 ITD (hemizygous)	2
MOLM14	FLT3 ITD	3
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*

* tested up to 10 000 nM.
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).
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.

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