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Quizartinib (AC220) FLT3-remmer

Name: Quizartinib (AC220)
Brand: Selleck Chemicals
SKU: S1526
Rating: 5 (153 reviews)

Cat.nr.S1526

Quizartinib (AC220) is een tweede generatie FLT3-remmer voor Flt3(ITD/WT) met een IC50 van respectievelijk 1,1 nM/4,2 nM in MV4-11 en RS4;11 cellen, 10 keer selectiever voor Flt3 dan KIT, PDGFRα, PDGFRβ, RET en CSF-1R. Quizartinib (AC220) induceert apoptosis van tumorcellen. Fase 3.

Quizartinib (AC220) Target Protein Ligand chemisch Chemical Structure

Chemische structuur

Molecuulgewicht: 560.67

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Batch: Zuiverheid: 99.52%

99.52

Gerelateerde doelwitten	EGFR VEGFR JAK PDGFR FGFR Src HIF FLT FLT3 HER2
Overig Target Protein Ligand Inhibitoren	(+)-JQ1 BI-4464

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Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	PMID
Pat.375	Growth Inhibition Assay			IC50=503 nM	23497317
Pat.305	Growth Inhibition Assay			IC50=7079 nM	23497317
Pat.299	Growth Inhibition Assay			IC50=7248 nM	23497317
Pat.279	Growth Inhibition Assay			IC50=3434 nM	23497317
Pat.221	Growth Inhibition Assay			IC50=675 nM	23497317
MOLM14	Growth Inhibition Assay			IC50< 1 nM	23497317
MV4;11	Growth Inhibition Assay			IC50< 1 nM	23497317
EOL-1	Growth Inhibition Assay			IC50=1 nM	23497317
M-07e + SCF	Growth Inhibition Assay			IC50=77 nM	23497317
Kasumi-1	Growth Inhibition Assay			IC50=36 nM	23497317
p815	Growth Inhibition Assay			IC50=445 nM	23497317
HMC1.2	Growth Inhibition Assay			IC50=1727 nM	23497317
HMC1.1	Growth Inhibition Assay			IC50=14 nM	23497317
8226/MR20	Cell Viability Assays	0.1 µM	96 h	sensitizes K562/ABCG2 cells to	23967177
K562/ABCG2	Cell Viability Assays	0.1/0.5/1 µM	96 h	sensitizes K562/ABCG2 cells to	23967177
MCF-7 FLV1000	Kinase Assay	0–30 µM	5 min	decreases [125I]-IAAP photolabeling of ABCB2 at IC50 of 0.07 μM	23967177
MCF-7 FLV1000	Kinase Assay	0–30 µM	5 min	decreases [125I]-IAAP photolabeling of ABCB1 at IC50 of 3.3 μM	23967177
K562/ABCG2	Function Assay	0.1-10 μM	30 min	enhances uptake of substrates of ABCG2 and ABCB1 in a concentration-dependent manner	23967177
8226/MR20	Function Assay	0.1-10 μM	30 min	enhances uptake of substrates of ABCG2 and ABCB1 in a concentration-dependent manner	23967177
K562/ABCB1	Function Assay	0.1-10 μM	30 min	enhances uptake of substrates of ABCG2 and ABCB1 in a concentration-dependent manner	23967177
HL60/VCR	Function Assay	0.1-10 μM	30 min	enhances uptake of substrates of ABCG2 and ABCB1 in a concentration-dependent manner	23967177
Pat.379	Growth Inhibition Assay			IC50=806 nM	23497317
Pat.368	Growth Inhibition Assay			IC50=2700 nM	23497317
Pat.601	Growth Inhibition Assay			IC50=1153 nM	23497317
HMC1.1	Apoptosis Assay			IC50=31 nM	23497317
p815	Apoptosis Assay			IC50=341 nM	23497317
Kasumi-1	Apoptosis Assay			IC50=67 nM	23497317
M-07e + SCF	Apoptosis Assay			IC50=78 nM	23497317
EOL-1	Apoptosis Assay			IC50< 1 nM	23497317
MV4;11	Apoptosis Assay			IC50=2 nM	23497317
MOLM14	Apoptosis Assay			IC50=3 nM	23497317
GIST822	Apoptosis Assay			IC50=109 nM	23497317
Pat.368	Apoptosis Assay			IC50=2998 nM	23497317
Pat.601	Apoptosis Assay			IC50=876 nM	23497317
MV4-11	Growth Inhibition Assay		72 h	IC50=0.3 nM	23412931
MOLM-14	Growth Inhibition Assay		72 h	IC50=0.1 nM	23412931
SEM-K2	Growth Inhibition Assay		72 h	IC50=0.4 nM	23412931
RS4;11	Growth Inhibition Assay		72 h	IC50>10,000 nM	23412931
THP-1	Growth Inhibition Assay		72 h	IC50>10,000 nM	23412931
MV4-11	Apoptosis Assay		8/24 h	induces significant and dose-dependent PARP cleavage and accumulation of sub-2N DNA	23412931
MOLM-14	Apoptosis Assay		8/24 h	induces significant and dose-dependent PARP cleavage and accumulation of sub-2N DNA	23412931
SEM-K2	Apoptosis Assay		8/24 h	induces significant and dose-dependent PARP cleavage and accumulation of sub-2N DNA	23412931
AML	Cytotoxicity assay			Cytotoxicity against human AML cells isolated from relapsed acute myeloid leukemia patient harboring FLT3 ITD mutation by MTT assay, IC50 = 0.0003 μM.	19654408
MV4-11	Cytotoxicity assay		72 hrs	Cytotoxicity against human MV4-11 cells after 72 hrs by cell titer-blue assay, IC50 = 0.00056 μM.	19654408
blast cells	Function assay		2 hrs	Inhibition of FLT3 ITD mutant autophosphorylation in human blast cells after 2 hrs by electrochemiluminescence, IC50 = 0.0008 μM.	19654408
RS4-11	Function assay		2 hrs	Inhibition of FLT3 ITD mutant autophosphorylation in human RS4-11 cells after 2 hrs by electrochemiluminescence assay, IC50 = 0.0011 μM.	19654408
AML	Function assay			Inhibition of FLT3 autophosphorylation in human AML cells isolated from relapsed acute myeloid leukemia patient by Western blotting, IC50 = 0.002 μM.	19654408
RS4-11	Function assay		2 hrs	Inhibition of FLT3 autophosphorylation in human RS4-11 cells after 2 hrs by electrochemiluminescence assay, IC50 = 0.0042 μM.	19654408
MV4-11	Antitumor assay	10 mg/kg	60 days	Antitumor activity against human MV4-11 cells xenografted mouse model assessed as inhibition of tumor regrowth at at 10 mg/kg, po 60 days post treatment	19654408
MV4-11	Antitumor assay	1 mg/kg/day	30 days	Antitumor activity against human MV4-11 cells xenografted mouse bone marrow engraftment model assessed as increase mouse life span at 1 mg/kg/day, po for 30 days measured on day 77 post dose	19654408
MV4-11	Antiproliferative assay		72 hrs	Antiproliferative activity against human MV4-11 cells after 72 hrs by cell titer-blue cell viability assay, IC50 = 0.00056 μM.	19754199
HEK293	Function assay			Binding affinity to FLT3 catalytic domain expressed in HEK293 cells by competitive binding assay, Kd = 0.0016 μM.	19754199
MV4-11	Antitumor assay	1 mg/kg	28 days	Antitumor activity against human MV4-11 cells xenografted in athymic nude mouse assessed as inhibition of tumor growth at 1 mg/kg, po QD for 28 days measured during dosing period	19754199
MV4-11	Antitumor assay	3 mg/kg	28 days	Antitumor activity against human MV4-11 cells xenografted in athymic nude mouse assessed as tumor growth regression at 3 mg/kg, po QD for 28 days measured after dosing period	19754199
MV4-11	Antitumor assay	10 mg/kg	28 days	Antitumor activity against human MV4-11 cells xenografted in athymic nude mouse assessed as tumor growth regression at 10 mg/kg, po QD for 28 days measured after dosing period	19754199
MV4-11	Antitumor assay	3 mg/kg	28 days	Antitumor activity against human MV4-11 cells xenografted in athymic nude mouse assessed as suppression of tumor volume at 3 mg/kg, po QD for 28 days measured after dosing period	19754199
MV4-11	Antitumor assay	10 mg/kg	28 days	Antitumor activity against human MV4-11 cells xenografted in athymic nude mouse assessed as suppression of tumor volume at 10 mg/kg, po QD for 28 days measured after dosing period	19754199
MV4-11	Antitumor assay	10 mg/kg	28 days	Antitumor activity against human MV4-11 cells xenografted in athymic nude mouse assessed as inhibition of tumor growth at 10 mg/kg, po QD for 28 days measured after 32 days postdose	19754199
MOLM13	Antiproliferative assay			Antiproliferative activity against human MOLM13 cells expressing FLT3-ITD mutant, GI50 = 0.004 μM.	22726931
MV411	Growth inhibition assay		48 hrs	Growth inhibition of human MV411 cells after 48 hrs by XTT assay, GI50 = 3.31 μM.	25108079
THP1	Growth inhibition assay		48 hrs	Growth inhibition of human THP1 cells after 48 hrs by XTT assay, GI50 = 5.574 μM.	25108079
HL60	Growth inhibition assay		48 hrs	Growth inhibition of human HL60 cells after 48 hrs by XTT assay, GI50 = 8.014 μM.	25108079
32D	Function assay		72 hrs	Inhibition of human FLT3 ITD mutant expressed in mouse 32D cells assessed as cell growth inhibition after 72 hrs by MTS assay, GI50 = 0.00001 μM.	26081023
MV4-11	Function assay		72 hrs	Inhibition of FLT3 ITD homozygous mutant in human MV4-11 cells assessed as cell growth inhibition after 72 hrs by MTS assay, GI50 = 0.003 μM.	26081023
MOLM-13	Function assay		72 hrs	Inhibition of FLT3 ITD heterozygous mutant in human MOLM-13 cells assessed as cell growth inhibition after 72 hrs by MTS assay, GI50 = 0.004 μM.	26081023
32D	Function assay		72 hrs	Inhibition of drug resistant human FLT3 ITD D835Y mutant expressed in mouse 32D cells assessed as cell growth inhibition after 72 hrs by MTS assay, GI50 = 0.016 μM.	26081023
32D	Function assay		72 hrs	Inhibition of drug resistant human FLT3 ITD D835V mutant expressed in mouse 32D cells assessed as cell growth inhibition after 72 hrs by MTS assay, GI50 = 0.027 μM.	26081023
Sf9	Function assay		4 hrs	Inhibition of wild type GST-tagged FLT3 kinase domain (Y567 to S993) (unknown origin) expressed in baculovirus infected insect Sf9 cells using Her2 peptide as substrate after 4 hrs by Kinase-Glo assay, IC50 = 0.069 μM.	26081023
32D	Function assay		72 hrs	Inhibition of drug resistant human FLT3 ITD D835F mutant expressed in mouse 32D cells assessed as cell growth inhibition after 72 hrs by MTS assay, GI50 = 0.15 μM.	26081023
32D	Function assay		72 hrs	Inhibition of drug resistant human FLT3 ITD F691L mutant expressed in mouse 32D cells assessed as cell growth inhibition after 72 hrs by MTS assay, GI50 = 0.22 μM.	26081023
Sf9	Function assay		120 mins	Inhibition of recombinant GST-tagged VEGFR2 kinase domain (V789 to V1356) (unknown origin) expressed in insect Sf9 cells using polyGlu4:Tyr peptide as substrate after 120 mins by Kinase-Glo assay, IC50 = 0.43 μM.	26081023
RS4:11	Function assay		72 hrs	Inhibition of wild type homozygous FLT3 in human RS4:11 cells assessed as cell growth inhibition after 72 hrs by MTS assay, GI50 = 2.2 μM.	26081023
MV4-11	Antitumor assay	10 mg/kg	48 days	Antitumor activity against human MV4-11 cells xenografted in nude mouse assessed as tumor regression at 10 mg/kg, po qd administered on day 1 to 5 measured during 48 days post last dose	26081023
MV4-11	Antitumor assay	10 mg/kg	48 days	Antitumor activity against human MV4-11 cells xenografted in nude mouse assessed as tumor regression at 10 mg/kg, po qd administered on day 8 to 12 measured during 48 days post last dose	26081023
MV4-11	Cytotoxicity assay		72 hrs	Cytotoxicity against human MV4-11 cells incubated for 72 hrs by MTT assay, IC50 = 0.00068 μM.	26142317
Sf21	Function assay		15 mins	Inhibition of recombinant human FLT3 expressed in insect Sf21 cells preincubated for 15 mins followed by poly(Glu:Tyr) substrate addition for 30 mins in presence of [gamma-32P]ATP by TR-FRET assay, IC50 = 0.02608 μM.	27187860
MV4-11	Growth inhibition assay		48 hrs	Growth inhibition of human MV4-11 cells expressing FLT3-ITD after 48 hrs by XTT assay, GI50 = 1.103 μM.	27187860
HL60	Growth inhibition assay		48 hrs	Growth inhibition of human HL60 cells expressing wild type FLT-3 after 48 hrs by XTT assay, GI50 = 1.488 μM.	27187860
THP1	Growth inhibition assay		48 hrs	Growth inhibition of human THP1 cells expressing wild type FLT-3 after 48 hrs by XTT assay, GI50 = 2.125 μM.	27187860
K562	Growth inhibition assay		48 hrs	Growth inhibition of human K562 cells after 48 hrs by XTT assay, GI50 = 2.638 μM.	27187860
Sf21	Function assay		10 mins	Inhibition of N-terminal GST-tagged recombinant human wild-type FLT3 (564 to end residues) expressed in baculovirus infected sf21 cells using Abltide as substrate in presence of [gamma33P]ATP after 10 mins by scintillation counting method, IC50 = 0.0255 μM.	28043794
Sf21	Function assay		10 mins	Inhibition of N-terminal GST-tagged recombinant human wild-type FLT3 (564 to end residues) D835Y mutant expressed in baculovirus infected sf21 cells using Abltide as substrate in presence of [gamma33P]ATP after 10 mins by scintillation counting method, IC50 = 0.2355 μM.	28043794
MV4-11	Growth inhibition assay			Growth inhibition of human MV4-11 cells harboring FLT3-ITD mutant by XTT assay, GI50 = 1.103 μM.	28043794
THP1	Growth inhibition assay			Growth inhibition of human THP1 cells harboring wild-type FLT3 by XTT assay, GI50 = 2.125 μM.	28043794
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against mouse BAF3 cells harboring FLT3-ITD-D835G mutation after 72 hrs by CellTiter-Glo assay, GI50 = 0.0003 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against mouse BAF3 cells harboring FLT3-ITD-D835A mutation after 72 hrs by CellTiter-Glo assay, GI50 = 0.0003 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against mouse BAF3 cells harboring FLT3-D835H mutation after 72 hrs by CellTiter-Glo assay, GI50 = 0.0003 μM.	28956923
MOLM13	Antiproliferative assay		72 hrs	Antiproliferative activity against human MOLM13 cells harboring FLT3-ITD mutation after 72 hrs by CellTiter-Glo assay, GI50 = 0.0003 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against mouse BAF3 cells expressing TEL-fused FLT3 kinase after 72 hrs by CellTiter-Glo assay, GI50 = 0.0003 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against mouse BAF3 cells harboring FLT3-ITD-D835N mutation after 72 hrs by CellTiter-Glo assay, GI50 = 0.0003 μM.	28956923
MOLM14	Antiproliferative assay		72 hrs	Antiproliferative activity against human MOLM14 cells harboring FLT3-ITD mutation after 72 hrs by CellTiter-Glo assay, GI50 = 0.0003 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against mouse BAF3 cells harboring FLT3-ITD mutation after 72 hrs by CellTiter-Glo assay, GI50 = 0.0003 μM.	28956923
MV4-11	Antiproliferative assay		72 hrs	Antiproliferative activity against human MV4-11 cells after 72 hrs by CellTiter-Glo assay, GI50 = 0.0003 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against TEL-fused PDGFRalpha-transformed mouse BAF3 cells after 72 hrs by CellTiter-Glo assay, GI50 = 0.0003 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against mouse BAF3 cells harboring FLT3-D835Y mutation after 72 hrs by CellTiter-Glo assay, GI50 = 0.002 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against TEL-fused PDGFRbeta-transformed mouse BAF3 cells after 72 hrs by CellTiter-Glo assay, GI50 = 0.0044 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against mouse BAF3 cells harboring FLT3-D835V mutation after 72 hrs by CellTiter-Glo assay, GI50 = 0.011 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against mouse BAF3 cells harboring FLT3-ITD-D835del mutation after 72 hrs by CellTiter-Glo assay, GI50 = 0.012 μM.	28956923
Sf9	Function assay		1 hr	Inhibition of human MV4-11 cells-derived His-tagged FLT3 ITD mutant (564 to 993 residues) expressed in baculovirus infected sf9 cells using poly (4:1 Glu, Tyr) as substrate after 1 hr by ADP-Glo kinase assay, IC50 = 0.0168 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against TEL-fused cKIT-transformed mouse BAF3 cells after 72 hrs by CellTiter-Glo assay, GI50 = 0.017 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against TEL-fused CSF1R-transformed mouse BAF3 cells after 72 hrs by CellTiter-Glo assay, GI50 = 0.024 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against mouse BAF3 cells harboring FLT3-ITD-D835Y mutation after 72 hrs by CellTiter-Glo assay, GI50 = 0.028 μM.	28956923
Sf9	Function assay		1 hr	Inhibition of human HL60 cells-derived His-tagged FLT3 (564 to 993 residues) expressed in baculovirus infected sf9 cells using poly (4:1 Glu, Tyr) as substrate after 1 hr by ADP-Glo kinase assay, IC50 = 0.0304 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against mouse BAF3 cells harboring FLT3-ITD-D835I mutation after 72 hrs by CellTiter-Glo assay, GI50 = 0.056 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against TEL-fused DDR2-transformed mouse BAF3 cells after 72 hrs by CellTiter-Glo assay, GI50 = 0.11 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against TEL-fused DDR1-transformed mouse BAF3 cells after 72 hrs by CellTiter-Glo assay, GI50 = 0.12 μM.	28956923
CMK	Antiproliferative assay		72 hrs	Antiproliferative activity against human CMK cells expressing FLT3 kinase after 72 hrs by CellTiter-Glo assay, GI50 = 0.12 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against TEL-fused RET-transformed mouse BAF3 cells after 72 hrs by CellTiter-Glo assay, GI50 = 0.13 μM.	28956923
HL60	Antiproliferative assay		72 hrs	Antiproliferative activity against human HL60 cells expressing FLT3 kinase after 72 hrs by CellTiter-Glo assay, GI50 = 0.13 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against TEL-fused FLT4-transformed mouse BAF3 cells after 72 hrs by CellTiter-Glo assay, GI50 = 0.27 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against mouse BAF3 cells harboring FLT3-K663Q mutation after 72 hrs by CellTiter-Glo assay, GI50 = 0.37 μM.	28956923
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against TEL-fused LCK-transformed mouse BAF3 cells after 72 hrs by CellTiter-Glo assay, GI50 = 0.4 μM.	28956923
U937	Antiproliferative assay		72 hrs	Antiproliferative activity against human U937 cells expressing FLT3 kinase after 72 hrs by CellTiter-Glo assay, GI50 = 1.2 μM.	28956923
SKM1	Antiproliferative assay		72 hrs	Antiproliferative activity against human SKM1 cells expressing FLT3 kinase after 72 hrs by CellTiter-Glo assay, GI50 = 1.3 μM.	28956923
NB4	Antiproliferative assay		72 hrs	Antiproliferative activity against human NB4 cells expressing FLT3 kinase after 72 hrs by CellTiter-Glo assay, GI50 = 7.3 μM.	28956923
MOLM13	Cell cycle assay	100 nM	12 hrs	Cell cycle arrest in human MOLM13 cells assessed as accumulation at G0/G1 phase at 100 nM after 12 hrs by propidium iodide staining based-FACS analysis	28956923
MOLM14	Cell cycle assay	100 nM	12 hrs	Cell cycle arrest in human MOLM14 cells assessed as accumulation at G0/G1 phase at 100 nM after 12 hrs by propidium iodide staining based-FACS analysis	28956923
MOLM13	Apoptosis assay	100 nM	12 hrs	Induction of apoptosis in human MOLM13 cells assessed as cleavage of PARP at 100 nM after 12 hrs by immunoblotting method	28956923
MV4-11	Apoptosis assay	100 nM	48 hrs	Induction of apoptosis in human MV4-11 cells assessed as cleavage of PARP at 100 nM after 48 hrs by immunoblotting method	28956923
MOLM13	Apoptosis assay	100 nM	12 hrs	Induction of apoptosis in human MOLM13 cells assessed as cleavage of caspase-3 at 100 nM after 12 hrs by immunoblotting method	28956923
MOLM14	Apoptosis assay	100 nM	24 hrs	Induction of apoptosis in human MOLM14 cells assessed as cleavage of PARP at 100 nM after 24 hrs by immunoblotting method	28956923
MOLM14	Apoptosis assay	100 nM	24 hrs	Induction of apoptosis in human MOLM14 cells assessed as cleavage of caspase-3 at 100 nM after 24 hrs by immunoblotting method	28956923
MV4-11	Apoptosis assay	100 nM	48 hrs	Induction of apoptosis in human MV4-11 cells assessed as cleavage of caspase-3 at 100 nM after 48 hrs by immunoblotting method	28956923
MV4-11	Cell cycle assay	100 nM	12 hrs	Cell cycle arrest in human MV4-11 cells assessed as accumulation at G0/G1 phase at 100 nM after 12 hrs by propidium iodide staining based-FACS analysis	28956923
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
U-2 OS	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
MOLM13	Growth inhibition assay		72 hrs	Growth inhibition of human MOLM13 cells after 72 hrs by calcein AM dye-based fluorescence assay, GI50 = 0.002 μM.	29672049
MV4-11	Growth inhibition assay		72 hrs	Growth inhibition of human MV4-11 cells after 72 hrs by calcein AM dye-based fluorescence assay, GI50 = 0.003 μM.	29672049
BA/F3	Function assay		72 hrs	Inhibition of FLT3 ITD mutant (unknown origin) transfected in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by calcein AM dye-based fluorescence assay, GI50 = 0.007 μM.	29672049
Sf9	Function assay			Inhibition of N-terminal GST/His6-fused recombinant human FLT3 (R571 to S993 residues) ITD mutant expressed in Sf9 insect cells using poly (Ala,Glu,Lys,Tyr) 6:2:5:1 hydrobromide as substrate in presence of [gamma-33P]ATP, IC50 = 0.01 μM.	29672049
Sf9	Function assay			Inhibition of N-terminal GST/His6-fused recombinant wild type human FLT3 (R571 to S993 residues) expressed in Sf9 insect cells using poly (Ala,Glu,Lys,Tyr) 6:2:5:1 hydrobromide as substrate in presence of [gamma-33P]ATP, IC50 = 0.036 μM.	29672049
Kasumi-1	Growth inhibition assay		72 hrs	Growth inhibition of human Kasumi-1 cells after 72 hrs by calcein AM dye-based fluorescence assay, GI50 = 0.064 μM.	29672049
Sf9	Function assay			Inhibition of N-terminal GST/His6-fused recombinant human FLT3 (R571 to S993 residues) D835Y mutant expressed in Sf9 insect cells using poly (Ala,Glu,Lys,Tyr) 6:2:5:1 hydrobromide as substrate in presence of [gamma-33P]ATP, IC50 = 0.136 μM.	29672049
BA/F3	Growth inhibition assay		72 hrs	Growth inhibition of mouse BA/F3 cells after 72 hrs by calcein AM dye-based fluorescence assay, GI50 = 1.452 μM.	29672049
MV4-11	Function assay	0.01 to 100 nM	1 hr	Inhibition of FLT3 ITD mutant in human MV4-11 cells assessed as decrease in AKT phosphorylation at S473 at 0.01 to 100 nM after 1 hr by immunoblot analysis	29672049
MV4-11	Function assay	0.01 to 100 nM	1 hr	Inhibition of FLT3 ITD mutant in human MV4-11 cells assessed as decrease in MEK1/2 phosphorylation at S217/221 at 0.01 to 100 nM after 1 hr by immunoblot analysis	29672049
MV4-11	Function assay	1 nM	1 hr	Inhibition of FLT3 ITD mutant autophosphorylation at Y589/591 in human MV4-11 cells at 1 nM after 1 hr by immunoblot analysis	29672049
MV4-11	Function assay	1 nM	1 hr	Inhibition of FLT3 ITD mutant autophosphorylation at Y842 in human MV4-11 cells at 1 nM after 1 hr by immunoblot analysis	29672049
MV4-11	Function assay	0.01 to 100 nM	1 hr	Inhibition of FLT3 ITD mutant in human MV4-11 cells assessed as decrease in STAT5 phosphorylation at Y694 at 0.01 to 100 nM after 1 hr by immunoblot analysis	29672049
MV4-11	Function assay	0.01 to 100 nM	1 hr	Inhibition of FLT3 ITD mutant in human MV4-11 cells assessed as decrease in ERK1/2 phosphorylation at T202/Y204 at 0.01 to 100 nM after 1 hr by immunoblot analysis	29672049
MV4-11	Function assay	10 mg/kg	24 hrs	In vivo inhibition of FLT3 ITD mutant in human MV4-11 cells xenografted in athymic nu/nu mouse assessed as decrease in STAT5 phosphorylation at Y694 at 10 mg/kg, ip after 24 hrs by immunoblot method relative to control	29672049
MV4-11	Function assay	0.1 uM	4 hrs	Inhibition of FLT3 in human MV4-11 cells assessed as reduction in AKT phosphorylation at Ser473 residue at 0.1 uM after 4 hrs by Western blot analysis	29894944
MV4-11	Function assay	0.1 uM	4 hrs	Inhibition of FLT3 in human MV4-11 cells assessed as reduction in STAT5 phosphorylation at Tyr694 residue at 0.1 uM after 4 hrs by Western blot analysis	29894944
MV4-11	Function assay	0.1 uM	4 hrs	Inhibition of FLT3 in human MV4-11 cells assessed as reduction in ERK1/2 phosphorylation at Thr202/Tyr204 residues at 0.1 uM after 4 hrs by Western blot analysis	29894944
MV4-11	Function assay	0.1 uM	4 hrs	Inhibition of FLT3 phosphorylation at Tyr589/591 residues in human MV4-11 cells at 0.1 uM after 4 hrs by Western blot analysis	29894944
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit

Molecuulgewicht	560.67	Formule	C₂₉H₃₂N₆O₄S	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	950769-58-1	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	N/A			Smiles	CC(C)(C)C1=CC(=NO1)NC(=O)NC2=CC=C(C=C2)C3=CN4C5=C(C=C(C=C5)OCCN6CCOCC6)SC4=N3

Oplosbaarheid

In vitro
Batch:

DMSO : 100 mg/mL (178.35 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	0.500mg/ml (0.89mM)	Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme

Kenmerken	The most potent cellular FLT3-ITD inhibitor.
Targets/IC₅₀/Ki	FLT3 (ITD) (MV4-11 cells) 1.1 nM FLT3 (WT) (RS4;11 cells) 4.2 nM
In vitro	AC220, een unieke, potente en selectieve remmer van FLT3, heeft een hoge affiniteit voor FLT3 met een K_d-waarde van 1,6 nM. Deze verbinding remt de autofosforylering van FLT3 in de menselijke leukemiecellijnen MV4-11, die een homozygote FLT3-ITD-mutatie bevatten en FLT3-afhankelijk zijn, en RS4;11, die wild-type FLT3 tot expressie brengt, met respectievelijk IC50-waarden van 1,1 nM en 4,2 nM. Het is de meest potente cellulaire FLT3-ITD-remmer, wat leidt tot de meest significante remming van de MV4-11 celproliferatie met een IC50 van 0,56 nM vergeleken met alle andere FLT3-remmers waarvan de IC50-waarden variëren van 0,87 nM tot 64 nM. Dit chemische middel heeft geen remmende activiteit tegen de proliferatie van A375-cellen die een activerende mutatie in BRAF bevatten en niet FLT3-afhankelijk zijn, wat een grote kloof aangeeft tussen FLT3-remming en algemene cytotoxische effecten.
Kinase Assay	Remming van FLT3-autofosforylering
Kinase Assay	Om de remming van FLT3-autofosforylering te meten, worden MV4-11 of RS4;11 cellen 's nachts gekweekt in een serumarm medium (0,5% FBS) en de volgende dag gezaaid met een dichtheid van 400.000 cellen per putje in een 96-well plaat. De cellen worden gedurende 2 uur bij 37 °C geïncubeerd met verschillende concentraties van deze verbinding. Om FLT3-autofosforylering in RS4;11 cellen te induceren, wordt 100 ng/mL FLT3 ligand gedurende 15 minuten toegevoegd na de 2 uur durende incubatie met dit chemische middel. Cellysaten worden bereid en geïncubeerd in 96-well platen die vooraf gecoat zijn met een totale FLT3-opvangantistof. De gecoate platen worden geïncubeerd met ofwel een gebiotinyleerde antistof tegen FLT3 om totale FLT3 te detecteren, ofwel een antistof tegen fosfotyrosines om FLT3-autofosforylering te detecteren. In beide gevallen wordt een SULFO-getagde streptavidine secundaire antistof gebruikt voor elektrochemiluminescentiedetectie op het Meso Scale Discovery-platform. De concentratie van deze verbinding die FLT3-ITD- of TLT3-WT-autofosforylering met 50% remt, vertegenwoordigt de IC50-waarde
In vivo	Orale toediening van AC220 (10 mg/kg) induceert tijdsafhankelijke remming van FLT3-autofosforylering in het FLT3-ITD-afhankelijke MV4-11 tumor xenograft muismodel; de remming bedraagt 90% na 2 uur en 40% na 24 uur. Deze verbinding verlengt de overleving significant in een muismodel van FLT3-ITD AML met doses zo laag als 1 mg/kg oraal eenmaal daags toegediend. Behandeling met dit chemische middel van 10 mg/kg gedurende 28 dagen resulteert in snelle en volledige regressie van tumoren bij alle muizen zonder tumorgroei gedurende de 60 dagen na de behandeling. Het toont een significantere werkzaamheid vergeleken met sunitinib-behandeling, die ervoor zorgt dat tumoren langzaam krimpen en onmiddellijk weer beginnen te groeien na stopzetting van de behandeling bij alle muizen behalve één.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/19654408/

Toepassingen

Methoden	Biomarkers	PMID
Western blot	p-STAT5 / STAT5 / β-catenin / p-AKT / AKT / p-ERK / ERK / p-S6 / S6 phospho-FLT3 / FLT3	28625976
Immunofluorescence	WGA / FLT3	28895560
Growth inhibition assay	Cell viability	23967177

Informatie over klinische proeven

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT04473664	Completed	Hepatic Impairment\|Moderate Impaired Hepatic Function	Daiichi Sankyo	September 22 2020	Phase 1
NCT04459585	Completed	Healthy Subjects\|Drug-drug Interaction\|Pharmacokinetics\|Quizartinib	Daiichi Sankyo Co. Ltd.\|Daiichi Sankyo	August 28 2020	Early Phase 1
NCT04459598	Completed	Healthy Subjects\|Drug-drug Interaction\|Pharmacokinetics\|Quizartinib	Daiichi Sankyo Co. Ltd.\|Daiichi Sankyo	August 19 2020	Phase 1
NCT04209725	Terminated	Leukemia Myeloid Acute	SCRI Development Innovations LLC	June 3 2020	Phase 2

Technische ondersteuning

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Tel: +1-832-582-8158 Ext:3

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Veelgestelde vragen

Vraag 1:
Is it possible to alter the captisol concentration to make it more dissolvable i.e 20% or 25% captisol ?

Antwoord:
In 15% Captisol, it forms a suspension at 30mg/ml. Increasing the percentage of Captisol will not convert the mixture into solution. You can use suspension for oral gavage feeding.

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