Cart
Angiogenesis FLT Quizartinib

Quizartinib

Catalog No. T2066   CAS 950769-58-1
Synonyms: AC220

Quizartinib is an inhibitor of FLT3 (Kd: 1.6 nM) and demonstrates high selectivity for FLT3 when tested against a panel of 227 additional kinases.

Quizartinib, CAS 950769-58-1
Pack Size Availability Price/USD Quantity
5 mg In stock 60.00
10 mg In stock 80.00
25 mg In stock 120.00
50 mg In stock 145.00
100 mg In stock 238.00
1 mL * 10 mM (in DMSO) In stock 80.00
Bulk Inquiry
Get quote
Select Batch  
Purity 98.87%
Purity 99.42%
Purity 98.00%
Purity 99.42%
Biological Description
Chemical Properties
Storage & Solubility Information
Preparing Solutions
Description Quizartinib is an inhibitor of FLT3 (Kd: 1.6 nM) and demonstrates high selectivity for FLT3 when tested against a panel of 227 additional kinases.
Targets&IC50 FLT3 (ITD) ,   FLT3 (WT) ,   FLT3
In vitro The highest affinity target identified for Quizartinib (AC220) was FLT3. The only other kinases with binding constants within 10-fold that for FLT3 were the closely related receptor tyrosine kinases (RTKs) KIT, PDGFRA, PDGFRB, RET, and CSF1R, and only 4 additional kinases, also related RTKs (FLT1, FLT4, DDR1, VEGFR2), bound with Kds within 100-fold of that for FLT3. In primary cells, treatment with AC220 for 1 hour inhibited FLT3 autophosphorylation (IC50: 2 nM), comparable with the activity observed in the MV4-11 cell line. The primary cells were sensitive to AC220 (IC50: 0.3 nM), again comparable with the activity observed in the MV4-11 cell line [1]. It inhibits the proliferation of the human leukemia cell line MV4-11, which harbors a homozygous FLT3-ITD mutation, with an IC50 value of 0.56 nM [2].
In vivo Treatment with AC220 at 10 mg/kg resulted in rapid and complete regression of tumors in all animals, and no tumor regrowth was observed during the 60-day posttreatment observation period. AC220 prolonged survival in a dose-dependent manner. At 10 mg/kg, 80% of animals treated survived until the study was terminated on day 172, 119 days after discontinuation of treatment, corresponding to at least a 250% increase in life span (ILS). At the time the study was terminated the animals did not exhibit any signs of disease. At 1 mg/kg a significant increase in the mean survival time was observed, to 77 days. At the lowest dose tested of 0.1 mg/kg, a marginal 10% ILS relative to vehicle was observed [1]. At 1 mg/kg of AC220, tumor growth was completely inhibited during the dosing period, after which growth resumed. At 3 and 10 mg/kg of AC220, tumors regressed almost completely and the tumor volume stayed suppressed after dosing was halted. At 3 mg/kg, tumors appeared to regrow after day 49 (21 days post last dose), while there was no sign of tumor regrowth until day 60 (32 days post last dose) in the animals treated with 10 mg/kg of AC220 [2].
Kinase Assay KinomeScan kinase binding assays were performed as previously described. For the FLT3 assay, we used a kinase construct that spanned the catalytic domain only (amino acids 592 to 969 in NP_004110.2). This construct does not include the juxtamembrane domain and is designed to measure the intrinsic binding affinity of the open FLT3 active site for inhibitors [1].
Cell Research
MV4-11 and RS4;11 cells were cultured in Iscove media with 10% fetal bovine serum (FBS) and RPMI complete with 10% FBS, respectively. For proliferation assays, cells were cultured overnight in low serum media (0.5% FBS), then seeded in a 96-well plate at 40 000 cells per well. Inhibitors were added to the cells and incubated at 37°C for 72 hours. Cell viability was measured using the Cell Titer-Blue Cell Viability Assay. To measure inhibition of FLT3 autophosphorylation, cells were cultured in low serum media (0.5% FBS) overnight and seeded at a density of 400 000 cells per well in a 96-well plate the following day. The cells were incubated with inhibitors for 2 hours at 37°C. To induce FLT3 autophosphorylation in RS4;11 cells, 100 ng/mL FLT3 ligand was added for 15 minutes after the 2-hour compound incubation. Cell lysates were prepared and incubated in 96-well plates pre-coated with a total FLT3 capture antibody. The coated plates were incubated with either a biotinylated antibody against FLT3 to detect total FLT3 or an antibody against phosphotyrosines to detect FLT3 autophosphorylation. In both cases, a SULFO-tagged streptavidin secondary antibody was used for electrochemiluminescence detection on the Meso Scale Discovery platform [1].
Cell lines: MV4-11 and RS4;11 cells
Animal Research
The model was performed according to published procedures.20 For intravenous bone marrow engraftment, nonobese diabetic/severe combined immunodeficient mice were acclimated for 2 weeks before pretreatment with 150 mg/kg cyclophosphamide delivered intraperitoneally once a day for 2 days. After a 48-hour rest period, animals were given an intravenous injection of 5 × 10^6 MV4-11 cells into the tail vein. AC220 was formulated and delivered as described for pharmacokinetic studies [1].
Synonyms AC220
Purity 98.87%
Molecular Weight 560.67
Formula C29H32N6O4S
CAS No. 950769-58-1

Storage

0-4℃ for short term (days to weeks), or -20℃ for long term (months).

Solubility Information

DMSO: 33.2 mg/mL (59.21 mM)

Ethanol: <1 mg/mL

( < 1 mg/ml refers to the product slightly soluble or insoluble )

Solution 1

15% Captisol: 30 mg/mL

Citations

References and Literature
1. Zarrinkar PP, et al. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood, 2009, 114(14), 2984-2992. 2. Chao Q, et al. Identification of N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea dihydrochloride (AC220), a uniquely potent, selective, and efficacious FMS-like tyrosine kinase-3 (FLT3) inhibitor. J Med Chem. 2009 Dec 10;52(23):7808-16.

Related compound libraries

This product is contained In the following compound libraries:
Bioactive Compound Library Inhibitor Library Anti-cancer Compound Library Clinical Compound Library Apoptosis Compound Library Autophagy Compound Library Tyrosine kinase inhibitor library Cytokine Inhibitor Library Kinase Inhibitor Library Anti-cancer Approved drug Library Anti-cancer Clinical Compound Library Anti-Cardiovascular Disease Compound Library Angiogenesis related Compound Library Anti-aging Compound Library Hematonosis Compound Library Anti-cancer Active Compound library Anti-cancer Drug library Drug Repurposing Library Drug-induced Liver Injury (DILI) Compound Library Covalent Inhibitor Library FDA Approved & Pharmacopeial Drug Library

Related Products

Related compounds with same targets
NVP-AEW541 Sorafenib Sorafenib tosylate KW2449 3-Hydroxy Midostaurin Rigosertib TAS05567 UNC2541

Dose Conversion

You can also refer to dose conversion for different animals. More

In vivo Formulation Calculator (Clear solution)

Step One: Enter information below
Dosage
mg/kg
Average weight of animals
g
Dosing volume per animal
ul
Number of animals
Step Two: Enter the in vivo formulation
% DMSO
%
% Tween 80
% ddH2O
Calculate Reset

Calculator

Molarity Calculator
Dilution Calculator
Reconstitution Calculation
Molecular Weight Calculator
=
X
X

Molarity Calculator allows you to calculate the

  • Mass of a compound required to prepare a solution of known volume and concentration
  • Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Concentration of a solution resulting from a known mass of compound in a specific volume
See Example

An example of a molarity calculation using the molarity calculator
What is the mass of compound required to make a 10 mM stock solution in 10 ml of water given that the molecular weight of the compound is 197.13 g/mol?
Enter 197.13 into the Molecular Weight (MW) box
Enter 10 into the Concentration box and select the correct unit (millimolar)
Enter 10 into the Volume box and select the correct unit (milliliter)
Press calculate
The answer of 19.713 mg appears in the Mass box

X
=
X

Calculator the dilution required to prepare a stock solution

Calculate the dilution required to prepare a stock solution
The dilution calculator is a useful tool which allows you to calculate how to dilute a stock solution of known concentration. Enter C1, C2 & V2 to calculate V1.

See Example

An example of a dilution calculation using the Tocris dilution calculator
What volume of a given 10 mM stock solution is required to make 20ml of a 50 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=50 μM, V2=20 ml and V1 is the unknown:
Enter 10 into the Concentration (start) box and select the correct unit (millimolar)
Enter 50 into the Concentration (final) box and select the correct unit (micromolar)
Enter 20 into the Volume (final) box and select the correct unit (milliliter)
Press calculate
The answer of 100 microliter (0.1 ml) appears in the Volume (start) box

=
/

Calculate the volume of solvent required to reconstitute your vial.

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial.
Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

g/mol

Enter the chemical formula of a compound to calculate its molar mass and elemental composition

Tip: Chemical formula is case sensitive: C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed n the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

bottom

Tech Support

Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.