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Quizartinib (AC220) FLT3 Inhibitor

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

Kat.-Nr.S1526

Quizartinib (AC220) ist ein FLT3-Inhibitor der zweiten Generation für Flt3(ITD/WT) mit einer IC50 von 1,1 nM/4,2 nM in MV4-11- bzw. RS4;11-Zellen, 10-mal selektiver für Flt3 als KIT, PDGFRα, PDGFRβ, RET und CSF-1R. Quizartinib (AC220) induziert die Apoptose von Tumorzellen. Phase 3.

Quizartinib (AC220) Target Protein Ligand chemisch Chemical Structure

Chemische Struktur

Molekulargewicht: 560.67

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Qualitätskontrolle

Charge: Reinheit: 99.52%

99.52

Verwandte Ziele	EGFR VEGFR JAK PDGFR FGFR Src HIF FLT FLT3 HER2
Weitere Target Protein Ligand Inhibitoren	(+)-JQ1 BI-4464

Zellkultur, Behandlung & Arbeitskonzentration

Zelllinien	Assay-Typ	Konzentration	Inkubationszeit	Aktivitätsbeschreibung	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
Klicken Sie hier, um weitere experimentelle Daten zu Zelllinien anzuzeigen

Chemische Informationen, Lagerung & Stabilität

Molekulargewicht	560.67	Formel	C₂₉H₃₂N₆O₄S	Lagerung (Ab dem Eingangsdatum)	3 Jahre-20°CPulver
CAS-Nr.	950769-58-1	SDF herunterladen		Lagerung von Stammlösungen	1 Jahr-80°Cin Lösungsmittel 1 Monat-20°Cin Lösungsmittel
Synonyme	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

Löslichkeit

In vitro
Charge:

DMSO : 100 mg/mL (178.35 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 100 mg/mL (178.35 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 33.2 mg/mL (59.21 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 33 mg/mL (58.85 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritätsrechner

Masse	Konzentration	Volumen	Molekulargewicht
=	×	×

Verdünnungsrechner Molekulargewichtsrechner

In vivo Charge:
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 Von Selleck Labs validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, kontaktieren Sie unser Verkaufsteam für kundenspezifische 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-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie die untenstehenden Informationen ein (Empfohlen: Ein zusätzliches Tier zur Berücksichtigung von Verlusten während des Experiments)

Dosierung: mg/kg Durchschnittsgewicht der Tiere: g Dosiervolumen pro Tier:μL Anzahl der Tiere:

Schritt 2: Geben Sie die In-vivo-Formulierung ein (Dies ist nur der Rechner, keine Formulierung. Bitte kontaktieren Sie uns zuerst, wenn es im Abschnitt "Löslichkeit" keine In-vivo-Formulierung gibt.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

Methode zur Herstellung der DMSO-Stammlösung: mg Wirkstoff vorgelöst in μL DMSO ( Konzentration der Stammlösung mg/mL, Bitte kontaktieren Sie uns zuerst, wenn die Konzentration die DMSO-Löslichkeit der Wirkstoffcharge überschreitet. )

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügenμL PEG300, mischen und klären, dann hinzufügenμL Tween 80, mischen und klären, dann hinzufügen μL ddH₂O, mischen und klären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügen μL Maisöl, mischen und klären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, das/die Lösungsmittel der Reihe nach hinzuzufügen. Sie müssen sicherstellen, dass die bei der vorherigen Zugabe erhaltene Lösung eine klare Lösung ist, bevor Sie mit der Zugabe des nächsten Lösungsmittels fortfahren. Physikalische Methoden wie Vortex, Ultraschall oder ein heißes Wasserbad können zur Unterstützung des Lösens verwendet werden.

Wirkmechanismus

Merkmale	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, ein einzigartiger, potenter und selektiver Inhibitor von FLT3, hat eine hohe Affinität zu FLT3 mit einem K_d-Wert von 1,6 nM. Diese Verbindung hemmt die Autophosphorylierung von FLT3 in den menschlichen Leukämiezelllinien MV4-11, die eine homozygote FLT3-ITD-Mutation aufweisen und FLT3-abhängig sind, sowie in RS4;11, die Wildtyp-FLT3 exprimiert, mit IC50-Werten von 1,1 nM bzw. 4,2 nM. Es ist der potenteste zelluläre FLT3-ITD-Inhibitor, der die signifikanteste Hemmung der MV4-11-Zellproliferation mit einer IC50 von 0,56 nM im Vergleich zu allen anderen FLT3-Inhibitoren, deren IC50-Werte zwischen 0,87 nM und 64 nM liegen, bewirkt. Diese Chemikalie hat keine hemmende Wirkung auf die Proliferation von A375-Zellen, die eine aktivierende Mutation in BRAF aufweisen und nicht FLT3-abhängig sind, was ein großes Fenster zwischen FLT3-Hemmung und allgemeinen zytotoxischen Effekten anzeigt.
Kinase-Assay	Inhibition der FLT3-Autophosphorylierung
Kinase-Assay	Zur Messung der Hemmung der FLT3-Autophosphorylierung werden MV4-11- oder RS4;11-Zellen über Nacht in Medien mit niedrigem Serumgehalt (0,5 % FBS) kultiviert und am nächsten Tag in einer Dichte von 400.000 Zellen pro Well in einer 96-Well-Platte ausgesät. Die Zellen werden 2 Stunden lang bei 37 °C mit verschiedenen Konzentrationen dieser Verbindung inkubiert. Um die FLT3-Autophosphorylierung in RS4;11-Zellen zu induzieren, werden nach der 2-stündigen Inkubation mit dieser Chemikalie 100 ng/mL FLT3 ligand für 15 Minuten hinzugefügt. Zelllysate werden hergestellt und in 96-Well-Platten inkubiert, die mit einem gesamten FLT3-Fangantikörper vorbeschichtet sind. Die beschichteten Platten werden entweder mit einem biotinylierten Antikörper gegen FLT3 zur Detektion des gesamten FLT3 oder einem Antikörper gegen Phosphotyrosine zur Detektion der FLT3-Autophosphorylierung inkubiert. In beiden Fällen wird ein SULFO-markierter Streptavidin-Sekundärantikörper zur elektrochemilumineszenten Detektion auf der Meso Scale Discovery-Plattform verwendet. Die Konzentration dieser Verbindung, die die FLT3-ITD- oder TLT3-WT-Autophosphorylierung um 50 % hemmt, stellt den IC50-Wert dar
In vivo	Die orale Verabreichung von AC220 (10 mg/kg) induziert eine zeitabhängige Hemmung der FLT3-Autophosphorylierung im FLT3-ITD-abhängigen MV4-11-Tumor-Xenograft-Mausmodell; die Hemmung beträgt 90 % nach 2 Stunden und 40 % nach 24 Stunden. Diese Verbindung verlängert das Überleben in einem Mausmodell von FLT3-ITD AML signifikant mit Dosen von nur 1 mg/kg, die einmal täglich oral verabreicht werden. Die Behandlung mit dieser Chemikalie bei 10 mg/kg für 28 Tage führt zu einer schnellen und vollständigen Regression der Tumoren bei allen Mäusen ohne Tumorwachstum während des 60-tägigen Nachbehandlungszeitraums. Sie zeigt eine signifikant höhere Wirksamkeit im Vergleich zur Sunitinib-Behandlung, die dazu führt, dass die Tumoren langsam schrumpfen und sofort nach Beendigung der Behandlung bei allen bis auf einer Maus wieder wachsen.
Literatur	[1] https://pubmed.ncbi.nlm.nih.gov/19654408/

Anwendungen

Methoden	Biomarker	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

Klinische Studieninformationen

(Daten von https://clinicaltrials.gov, aktualisiert am 2024-05-22)

NCT-Nummer	Rekrutierung	Erkrankungen	Sponsor/Kooperationspartner	Startdatum	Phasen
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

Technischer Support

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Häufig gestellte Fragen

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

Antwort:
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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