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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*

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*

  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.