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Quizartinib (AC220) inhibiteur de FLT3

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

Réf. CatalogueS1526

Quizartinib (AC220) est un inhibiteur de FLT3 de deuxième génération pour Flt3(ITD/WT) avec un IC50 de 1,1 nM/4,2 nM dans les cellules MV4-11 et RS4;11, respectivement, 10 fois plus sélectif pour Flt3 que KIT, PDGFRα, PDGFRβ, RET et CSF-1R. Quizartinib (AC220) induit l'apoptose des cellules tumorales. Phase 3.

Quizartinib (AC220) Target Protein Ligand produit chimique Chemical Structure

Structure chimique

Poids moléculaire: 560.67

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Contrôle Qualité

Lot : Pureté : 99.52%

99.52

Cibles apparentées	EGFR VEGFR JAK PDGFR FGFR Src HIF FLT FLT3 HER2
Autre Target Protein Ligand Inhibiteurs	(+)-JQ1 BI-4464

Culture cellulaire, traitement et concentration de travail

Lignées cellulaires	Type dessai	Concentration	Temps dincubation	Description de lactivité	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
Cliquez pour voir plus de données expérimentales sur la lignée cellulaire

Informations chimiques, stockage et stabilité

Poids moléculaire	560.67	Formule	C₂₉H₃₂N₆O₄S	Stockage (À compter de la date de réception)	3 ans-20°Cpoudre
N° CAS	950769-58-1	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	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

Solubilité

In vitro
Lot:

DMSO : 100 mg/mL (178.35 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Water : Insoluble

Ethanol : Insoluble

Calculateur de molarité

Masse	Concentration	Volume	Poids moléculaire
=	×	×

Calculateur de dilution Calculateur de poids moléculaire

In vivo Lot:
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 Validé par les laboratoires Selleck. Si vous avez besoin dajustements à cette formulation, contactez notre équipe commerciale pour des tests personnalisés.	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.

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Saisir les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant lexpérience)

Dosage : mg/kg Poids moyen des animaux : g Volume de dosage par animal :μL Nombre danimaux :

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter dabord sil ny a pas de formulation in vivo dans la section Solubilité.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Résultats du calcul :

Concentration de travail : mg/ml;

Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter dabord si la concentration dépasse la solubilité du DMSO du lot de médicament. )

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouterμL PEG300, mélanger et clarifier, puis ajouterμL Tween 80, mélanger et clarifier, puis ajouter μL ddH₂O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouter μL Huile de maïs, mélanger et clarifier.

Note : 1. Veuillez vous assurer que le liquide est clair avant dajouter le solvant suivant.
2. Assurez-vous dajouter le(s) solvant(s) dans lordre. Vous devez vous assurer que la solution obtenue, lors de lajout précédent, est une solution claire avant de procéder à lajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie chaud peuvent être utilisées pour faciliter la dissolution.

Mécanisme daction

Caractéristiques	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, un inhibiteur unique, puissant et sélectif de FLT3, a une affinité élevée pour FLT3 avec une valeur de K_d de 1,6 nM. Ce composé inhibe l'autophosphorylation de FLT3 dans les lignées cellulaires leucémiques humaines MV4-11 qui abritent une mutation FLT3-ITD homozygote et sont dépendantes de FLT3, et RS4;11 qui exprime le FLT3 de type sauvage avec des valeurs d'IC50 de 1,1 nM et 4,2 nM, respectivement. C'est l'inhibiteur cellulaire de FLT3-ITD le plus puissant, entraînant l'inhibition la plus significative de la prolifération des cellules MV4-11 avec une IC50 de 0,56 nM par rapport à tous les autres inhibiteurs de FLT3 dont les valeurs d'IC50 varient de 0,87 nM à 64 nM. Ce produit chimique n'a pas d'activité inhibitrice contre la prolifération des cellules A375 qui abritent une mutation activatrice de BRAF et ne sont pas dépendantes de FLT3, indiquant une large fenêtre entre l'inhibition de FLT3 et les effets cytotoxiques généraux.
Essai kinase	Inhibition de l'autophosphorylation de FLT3
Essai kinase	Pour mesurer l'inhibition de l'autophosphorylation de FLT3, les cellules MV4-11 ou RS4;11 sont cultivées dans un milieu à faible teneur en sérum (0,5 % de FBS) pendant une nuit et ensemencées à une densité de 400 000 cellules par puits dans une plaque à 96 puits le jour suivant. Les cellules sont incubées avec différentes concentrations de ce composé pendant 2 heures à 37 °C. Pour induire l'autophosphorylation de FLT3 dans les cellules RS4;11, 100 ng/mL de FLT3 ligand sont ajoutés pendant 15 minutes après l'incubation de 2 heures avec ce produit chimique. Les lysats cellulaires sont préparés et incubés dans des plaques à 96 puits pré-enduites d'un anticorps de capture total de FLT3. Les plaques enduites sont incubées soit avec un anticorps biotinylé contre FLT3 pour détecter le FLT3 total, soit avec un anticorps contre les phosphotyrosines pour détecter l'autophosphorylation de FLT3. Dans les deux cas, un anticorps secondaire streptavidine marqué SULFO est utilisé pour la détection par électrochimioluminescence sur la plateforme Meso Scale Discovery. La concentration de ce composé qui inhibe l'autophosphorylation de FLT3-ITD ou TLT3-WT de 50 % représente la valeur IC50
In vivo	L'administration orale d'AC220 (10 mg/kg) induit une inhibition temps-dépendante de l'autophosphorylation de FLT3 dans le modèle de souris xénogreffé de tumeur MV4-11 dépendant de FLT3-ITD ; l'inhibition étant de 90 % à 2 heures et de 40 % à 24 heures. Ce composé prolonge significativement la survie dans un modèle murin de LAM FLT3-ITD avec des doses aussi faibles que 1 mg/kg administrées oralement une fois par jour. Le traitement avec ce produit chimique à 10 mg/kg pendant 28 jours entraîne une régression rapide et complète des tumeurs chez toutes les souris sans repousse tumorale pendant la période de 60 jours post-traitement. Il affiche une efficacité plus significative par rapport au traitement par sunitinib qui provoque un rétrécissement lent des tumeurs et une reprise immédiate de la croissance dès l'arrêt du traitement chez toutes les souris sauf une.
Références	[1] https://pubmed.ncbi.nlm.nih.gov/19654408/

Applications

Méthodes	Biomarqueurs	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

Informations sur lessai clinique

(données du https://clinicaltrials.gov, mis à jour le 2024-05-22)

Numéro NCT	Recrutement	Conditions	Promoteur/Collaborateurs	Date de début	Phases
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

Support technique

Instructions de manipulation

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

Si vous avez dautres questions, veuillez laisser un message.

Foire aux questions

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

Réponse :
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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