1. Protein Tyrosine Kinase/RTK
    Autophagy
  2. FLT3
    Autophagy

Quizartinib (Synonyms: AC220)

Cat. No.: HY-13001 Purity: 99.46%
Handling Instructions

Quizartinib is a uniquely potent and selective Flt3 inhibitor with Kd (FLT3 binding affinity) of 1.6±0.7 nM in Biochemical assay.

For research use only. We do not sell to patients.
Quizartinib Chemical Structure

Quizartinib Chemical Structure

CAS No. : 950769-58-1

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 74 In-stock
5 mg USD 60 In-stock
10 mg USD 84 In-stock
50 mg USD 144 In-stock
100 mg USD 240 In-stock
200 mg USD 420 In-stock
500 mg USD 780 In-stock
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Customer Review

    Quizartinib purchased from MCE. Usage Cited in: Leukemia. 2012 Oct;26(10):2233-44.

    Drug combination effect on phosphorylation of AKT. Expression of phospho-AKT and total AKT in MOLM13 cells treated for 15 minutes with DMSO vehicle, PKC412 (2.5 nM), Dasatinib (165 nM), or a combination of both. Protein lysates are prepared from MOLM13 cells, and are analyzed via immunoblotting with antibodies to phospho-AKT and total AKT.

    Quizartinib purchased from MCE. Usage Cited in: Leukemia. 2012 Oct;26(10):2233-44.

    SCM stimulation of phospho-STAT5 and drug combination effect on phosphorylation of phospho-STAT5. Expression of phospho-STAT5 and total STAT5 in MOLM13 cells treated for 1.5 h with DMSO vehicle, PKC412 (5 nM), KIN40 (82.5 nM) or a combination of both. Results shown are representative of two independent experiments in which similar results are observed.

    Quizartinib purchased from MCE. Usage Cited in: Cancer Cell. 2014 Feb 10;25(2):226-42.

    Western blot for indicated proteins on lysates from FLT3-ITD-positive primary murine cells expressing either wild-type (WT) or constitutive active (SYK-TEL) SYK and treated for eight hours with indicated doses of AC220.

    Quizartinib purchased from MCE. Usage Cited in: Oncotarget. 2016 Jul 26;7(30):47018-47032.

    A. The established 32D cells are treated with Quizartinib for 2h, followed by 10 ng/mL FL stimulation for 10 minutes. Wt-FLT3 and mutant FLT3 are immunoprecipitated by each tag as indicated and subjected to Western blot. Phosphorylation levels of FLT3, STAT5, AKT and MAPK are examined. B. 32D cells are treated with Quizartinib at the indicated concentrations in the presence or absence of 10 ng/mL FL for 2 hours. Phosphorylation levels of FLT3, STAT5, AKT and MAPK are detected by Western blot.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    Quizartinib is a uniquely potent and selective Flt3 inhibitor with Kd (FLT3 binding affinity) of 1.6±0.7 nM in Biochemical assay.

    IC50 & Target

    Kd: 1.6±0.7 nM (Flt3)[1]

    In Vitro

    Quizartinib (AC220) is a novel compound expressly optimized as a FLT3 inhibitor for the treatment of acute myeloid leukemia (AML). Quizartinib inhibits FLT3-WT and FLT3-ITD autophosphorylation with IC50 of 4.2±0.3 nM and 1.1±0.1 nM, respectively. Quizartinib inhibits MV4-11 and A375 cells with IC50 of 0.56±0.3 nM and >10 000 nM, respectively. Quizartinib inhibits FLT3 with low nanomolar potency in cellular assays and is highly selective when screened against the majority of the human protein kinome[1].

    In Vivo

    Quizartinib (AC220) inhibits FLT3 activity in vivo, significantly extends survival in a mouse model of FLT3-ITD AML at doses as low as 1 mg/kg when dosed orally once a day, eradicates tumors in a FLT3-dependent mouse xenograft model at 10 mg/kg, and potently inhibits FLT3 activity in primary patient cells. The oral bioavailability of Quizartinib, determined in rats by comparing oral and intravenous pharmacokinetics at 3 mg/kg, is approximately 40%. A single 10 mg/kg dose of Quizartinib is administered by oral gavage, and mice are killed at 2 time points after dosing, using groups of 4 animals each. Quantitation of total FLT3 and phospho-FLT3 in tumor samples revealed time-dependent inhibition of FLT3 autophosphorylation. FLT3 activity is inhibited by 90% at 2 hours, and 40% at 24 hours after administration. The extent of inhibition therefore correlated well with the expected free Quizartinib plasma levels, based on pharmacokinetic experiments[1].

    Clinical Trial
    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 1.7836 mL 8.9179 mL 17.8358 mL
    5 mM 0.3567 mL 1.7836 mL 3.5672 mL
    10 mM 0.1784 mL 0.8918 mL 1.7836 mL
    Please refer to the solubility information to select the appropriate solvent.
    Kinase Assay
    [1]

    KinomeScan kinase binding assays are performed. For the FLT3 assay, a kinase construct that spanned the catalytic domain only (amino acids 592 to 969) is used. 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]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [1]

    Quizartinib (AC220) is dissolved in DMSO and stored, and then diluted with appropriate medium before use[1].

    MV4-11 and RS4;11 cells are cultured in Iscove media with 10% fetal bovine serum (FBS) and RPMI complete with 10% FBS, respectively. For proliferation assays, cells are cultured overnight in low serum media (0.5% FBS), then seeded in a 96-well plate at 40 000 cells per well. Inhibitors (e.g., Quizartinib) are added to the cells and incubated at 37°C for 72 hours. Cell viability is measured using the Cell Titer-Blue Cell Viability Assay. To measure inhibition of FLT3 autophosphorylation, cells are 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 are incubated with inhibitors (e.g., Quizartinib) for 2 hours at 37°C. To induce FLT3 autophosphorylation in RS4;11 cells, 100 ng/mL FLT3 ligand is added for 15 minutes after the 2-hour compound incubation. Cell lysates are prepared and incubated in 96-well plates precoated with a total FLT3 capture antibody. The coated plates are 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 is used for electrochemiluminescence detection on the Meso Scale Discovery platform[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Quizartinib (hydrochloride salt) is formulated in 22% hydroxypropyl-β-cyclodextrin (Mice)[1].

    Mice[1]
    Female NU/NU or severe combined immunodeficient mice are used. Quizartinib (hydrochloride salt) is formulated in 22% hydroxypropyl-β-cyclodextrin, CEP-701 is formulated in 20% gelucire 44/14 in water (vol/vol), MLN-518 and sunitinib are formulated in 10 mM sodium citrate (pH 3.5), PKC-412 is formulated in 3:1 gelucire 44/14-propylene glycol (vol/vol), and sorafenib (toluene sulfonate salt) is formulated in 80% PEG-400. Compound concentrations are chosen to deliver the desired dose in a volume of 10 mL/kg. Compounds are administered by oral gavage and plasma samples collected 0.25, 0.5, 1, 2, 4, 6, and 24 hours after dosing. To collect plasma samples, eye bleeds (150 μL) are taken semilongitudinally using 3 groups of 3 animals each, taking 2 to 3 time points per animal to obtain a total of 3 independent plasma concentration time courses. Plasma samples and controls (25 μL) are extracted with 4 volumes of acetonitrile containing an internal standard and analyzed by liquid chromatography tandem mass spectrometry. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    560.67

    Formula

    C₂₉H₃₂N₆O₄S

    CAS No.

    950769-58-1

    SMILES

    O=C(NC1=NOC(C(C)(C)C)=C1)NC2=CC=C(C=C2)C3=CN4C(SC5=CC(OCCN6CCOCC6)=CC=C45)=N3

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥ 33 mg/mL

    Quizartinib (AC220) is prepared in vehicle (22% hydroxypropyl-β-cyclodextrin in sterile water)[2].

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    References

    Purity: 99.46%

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