2. Protein Tyrosine Kinase/RTK PROTAC Apoptosis
  3. FLT3 Ligands for Target Protein for PROTAC Apoptosis
  4. Quizartinib

Quizartinib  (Synonyms: AC220; AC708)

Cat. No.: HY-13001 Purity: 98.83%
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Quizartinib (AC220) est un Flt3 inhibiteur puissant de la tyrosine kinase avec un Kd de 1,6 nM. Quizartinib peut être lié au ligand VHL via un linker optimisé pour former un dégradeur PROTAC FLT3. Quizartinib induit l'apoptose.

Quizartinib (AC220) ist ein oral wirksamer, hochselektiver und potenter Typ-II-FLT3 tyrosine kinase-Inhibitor der zweiten Generation mit einem Kd von 1,6 nM. Quizartinib hemmt die Wildtyp-FLT3- und FLT3-ITD-Autophosphorylierung in MV4-11-Zellen mit IC50s von 4,2 bzw. 1,1 nM. Quizartinib kann über einen optimierten Linker an den VHL-Liganden gebunden werden, um einen PROTAC FLT3-Degrader zu bilden. Quizartinib induziert die Apoptose.

Quizartinib (AC220) is an orally active, highly selective and potent second-generation type II FLT3 tyrosine kinase inhibitor, with a Kd of 1.6 nM. Quizartinib inhibits wild-type FLT3 and FLT3-ITD autophosphorylation in MV4-11 cells with IC50s of 4.2 and 1.1 nM, respectively. Quizartinib can be linked to the VHL ligand via an optimized linker to form a PROTAC FLT3 degrader. Quizartinib induces apoptosis.

For research use only. We do not sell to patients.

Quizartinib Chemical Structure

Quizartinib Chemical Structure

CAS No. : 950769-58-1

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 81 In-stock
Solution
10 mM * 1 mL in DMSO USD 81 In-stock
Solid
1 mg USD 26 In-stock
5 mg USD 66 In-stock
10 mg USD 92 In-stock
50 mg USD 158 In-stock
100 mg USD 264 In-stock
200 mg USD 462 In-stock
500 mg USD 858 In-stock
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Based on 34 publication(s) in Google Scholar

Other Forms of Quizartinib:

Quizartinib Related Antibodies

Top Publications Citing Use of Products

31 Publications Citing Use of MCE Quizartinib

WB

    Quizartinib purchased from MedChemExpress. Usage Cited in: J Med Chem. 2017 Oct 26;60(20):8407-8424.  [Abstract]

    Doseresponsive immunoblotting of the signaling pathway with the cells extracted from tumor tissues of the experimental animal after the 14 and 7 (AC220) treatments.

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

    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.

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

    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.

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Quizartinib (AC220) is an orally active, highly selective and potent second-generation type II FLT3 tyrosine kinase inhibitor, with a Kd of 1.6 nM. Quizartinib inhibits wild-type FLT3 and FLT3-ITD autophosphorylation in MV4-11 cells with IC50s of 4.2 and 1.1 nM, respectively. Quizartinib can be linked to the VHL ligand via an optimized linker to form a PROTAC FLT3 degrader. Quizartinib induces apoptosis[1].

    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].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    Quizartinib Related Antibodies
    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].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
    Clinical Trial
    Molecular Weight

    560.67

    Formula

    C29H32N6O4S
    CAS No.
    Appearance

    Solid

    Color

    White to light yellow

    SMILES

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

    Room temperature in continental US; may vary elsewhere.
    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 1 year
    -20°C 6 months
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 33 mg/mL (58.86 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    DMF : 10 mg/mL (17.84 mM; Need ultrasonic)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent 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
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

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    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

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    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMF    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 1 mg/mL (1.78 mM); Clear solution

    • Protocol 2

      Add each solvent one by one:  10% DMF    90% (20% SBE-β-CD in Saline)

      Solubility: ≥ 1 mg/mL (1.78 mM); Clear solution

    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

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    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
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    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation
    References
    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]

    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]

    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 SU 11248 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 Bay 43-9006 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

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMF / DMSO 1 mM 1.7836 mL 8.9179 mL 17.8358 mL 44.5895 mL
    5 mM 0.3567 mL 1.7836 mL 3.5672 mL 8.9179 mL
    10 mM 0.1784 mL 0.8918 mL 1.7836 mL 4.4590 mL
    15 mM 0.1189 mL 0.5945 mL 1.1891 mL 2.9726 mL
    DMSO 20 mM 0.0892 mL 0.4459 mL 0.8918 mL 2.2295 mL
    25 mM 0.0713 mL 0.3567 mL 0.7134 mL 1.7836 mL
    30 mM 0.0595 mL 0.2973 mL 0.5945 mL 1.4863 mL
    40 mM 0.0446 mL 0.2229 mL 0.4459 mL 1.1147 mL
    50 mM 0.0357 mL 0.1784 mL 0.3567 mL 0.8918 mL
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    Quizartinib Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    Quizartinib950769-58-1AC220 AC708AC 220AC-220AC708AC 708AC-708FLT3Ligands for Target Protein for PROTACApoptosisCluster of differentiation antigen 135CD135Fms like tyrosine kinase 3Target Protein-binding MoietyoralselectiveAMLacutemyeloidleukemiaFLT3-ITDmutationInhibitorinhibitorinhibit

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