Home Angiogenesis Target Protein Ligand chimico Quizartinib (AC220)

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Quizartinib (AC220) Inibitore di FLT3

N. Cat.S1526

Quizartinib (AC220) è un inibitore di FLT3 di seconda generazione per Flt3(ITD/WT) con IC50 di 1,1 nM/4,2 nM nelle cellule MV4-11 e RS4;11, rispettivamente, 10 volte più selettivo per Flt3 rispetto a KIT, PDGFRα, PDGFRβ, RET e CSF-1R. Quizartinib (AC220) induce l'apoptosi delle cellule tumorali. Fase 3.
Quizartinib (AC220) Target Protein Ligand chimico Chemical Structure

Struttura chimica

Peso molecolare: 560.67

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Controllo Qualità

Lotto: Purezza: 99.52%
99.52

Coltura cellulare, trattamento e concentrazione di lavoro

Linee cellulari Tipo di saggio Concentrazione Tempo di incubazione Formulazione Descrizione dellattività 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
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Informazioni chimiche, conservazione e stabilità

Peso molecolare 560.67 Formula

C29H32N6O4S

 Conservazione (Dalla data di ricezione)
N. CAS 950769-58-1 Scarica SDF Conservazione delle soluzioni stock

Sinonimi 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

Solubilità

In vitro
Lotto:

DMSO : 100 mg/mL (178.35 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Water : Insoluble

Ethanol : Insoluble

Calcolatore di Molarità

Massa Concentrazione Volume Peso molecolare
Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo
Lotto:

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante lesperimento)

mg/kg g μL

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non cè una formulazione in vivo nella sezione Solubilità.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH2O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nellaggiunta precedente, sia una soluzione limpida prima di procedere allaggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno dacqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo dazione

Caratteristiche
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 inibitore unico, potente e selettivo di FLT3, ha un'elevata affinità per FLT3 con un valore di Kd di 1,6 nM. Questo composto inibisce l'autofosforilazione di FLT3 nelle linee cellulari di leucemia umana MV4-11 che ospitano una mutazione FLT3-ITD omozigote e sono dipendenti da FLT3, e RS4;11 che esprime FLT3 di tipo selvaggio con valori di IC50 di 1,1 nM e 4,2 nM, rispettivamente. È il più potente inibitore cellulare di FLT3-ITD, portando alla più significativa inibizione della proliferazione delle cellule MV4-11 con IC50 di 0,56 nM rispetto a tutti gli altri inibitori di FLT3 i cui valori di IC50 vanno da 0,87 nM a 64 nM. Questa sostanza chimica non ha attività inibitoria contro la proliferazione delle cellule A375 che ospitano una mutazione attivante in BRAF e non sono dipendenti da FLT3, indicando un'ampia finestra tra l'inibizione di FLT3 e gli effetti citotossici generali.
Saggio chinasico
Inibizione dell'autofosforilazione di FLT3
Per misurare l'inibizione dell'autofosforilazione di FLT3, le cellule MV4-11 o RS4;11 vengono coltivate in un terreno a basso siero (0,5% FBS) durante la notte e seminate a una densità di 400 000 cellule per pozzetto in una piastra a 96 pozzetti il giorno successivo. Le cellule vengono incubate con diverse concentrazioni di questo composto per 2 ore a 37 °C. Per indurre l'autofosforilazione di FLT3 nelle cellule RS4;11, vengono aggiunti 100 ng/mL di FLT3 ligand per 15 minuti dopo l'incubazione di 2 ore con questa sostanza chimica. I lisati cellulari vengono preparati e incubati in piastre a 96 pozzetti pre-rivestite con un anticorpo di cattura totale di FLT3. Le piastre rivestite vengono incubate con un anticorpo biotinilato contro FLT3 per rilevare il FLT3 totale o un anticorpo contro le fosfotirosine per rilevare l'autofosforilazione di FLT3. In entrambi i casi, viene utilizzato un anticorpo secondario streptavidina con tag SULFO per la rilevazione mediante elettrochemiluminescenza sulla piattaforma Meso Scale Discovery. La concentrazione di questo composto che inibisce l'autofosforilazione di FLT3-ITD o TLT3-WT del 50% rappresenta il valore IC50
In vivo
La somministrazione orale di AC220 (10 mg/kg) induce un'inibizione tempo-dipendente dell'autofosforilazione di FLT3 nel modello murino di xenotrapianto tumorale MV4-11 dipendente da FLT3-ITD; l'inibizione è del 90% a 2 ore e del 40% a 24 ore. Questo composto prolunga significativamente la sopravvivenza in un modello murino di AML FLT3-ITD con dosi di soli 1 mg/kg somministrate per via orale una volta al giorno. Il trattamento con questa sostanza chimica a 10 mg/kg per 28 giorni si traduce in una regressione rapida e completa dei tumori in tutti i topi senza ricrescita del tumore durante il periodo di 60 giorni post-trattamento. Mostra un'efficacia più significativa rispetto al trattamento con sunitinib che provoca un lento restringimento dei tumori e una ripresa della crescita immediatamente dopo l'interruzione del trattamento in tutti i topi tranne uno.
Riferimenti

Applicazioni

Metodi Biomarcatori Immagini PMID
Western blot p-STAT5 / STAT5 / β-catenin / p-AKT / AKT / p-ERK / ERK / p-S6 / S6 phospho-FLT3 / FLT3
S1526-WB1
28625976
Immunofluorescence WGA / FLT3
S1526-IF1
28895560
Growth inhibition assay Cell viability
S1526-viability1
23967177

Informazioni sullo studio clinico

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT Reclutamento Condizioni Sponsor/Collaboratori Data di inizio Fasi
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

Supporto tecnico

Istruzioni per la manipolazione

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

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Domande Frequenti

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

Risposta:
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.