|
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.
