1. Protein Tyrosine Kinase/RTK
    PROTAC
    Apoptosis
    Autophagy
  2. FLT3
    Ligand for Target Protein for PROTAC
    Apoptosis
    Autophagy
  3. Quizartinib

Quizartinib (Synonyms: AC220)

製品番号: HY-13001 純度: 99.34%
取扱説明書

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.

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Quizartinib 構造式

Quizartinib 構造式

CAS 番号 : 950769-58-1

容量 価格(税別) 在庫状況 数量
無料サンプル (0.5-1 mg)   今すぐ申し込む  
10 mM * 1  mL in DMSO USD 74 在庫あり
Estimated Time of Arrival: December 31
5 mg USD 60 在庫あり
Estimated Time of Arrival: December 31
10 mg USD 84 在庫あり
Estimated Time of Arrival: December 31
50 mg USD 144 在庫あり
Estimated Time of Arrival: December 31
100 mg USD 240 在庫あり
Estimated Time of Arrival: December 31
200 mg USD 420 在庫あり
Estimated Time of Arrival: December 31
500 mg USD 780 在庫あり
Estimated Time of Arrival: December 31
1 g   お問い合わせ  
5 g   お問い合わせ  

* アイテムを追加する前、数量をご選択ください

カスタマーレビュー

Based on 17 publication(s) in Google Scholar

Top Publications Citing Use of Products

    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.

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

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

    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]

    体外実験

    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].

    体内実験

    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].

    臨床実験
    分子量

    560.67

    分子式

    C₂₉H₃₂N₆O₄S

    CAS 番号

    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

    輸送条件

    Room temperature in continental US; may vary elsewhere.

    保管条件
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    溶剤 & 溶解度
    体外: 

    DMSO : ≥ 33 mg/mL (58.86 mM)

    *"≥" 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
    10 mM 0.1784 mL 0.8918 mL 1.7836 mL
    *Please refer to the solubility information to select the appropriate solvent.
    体内:
    • 1.

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

    参考文献
    キナーゼ実験
    [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 はこれらの方法の精度を確認していません。 こちらは参照専用です。

    細胞実験
    [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 はこれらの方法の精度を確認していません。 こちらは参照専用です。

    動物実験
    [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 はこれらの方法の精度を確認していません。 こちらは参照専用です。

    参考文献
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    Keywords:

    QuizartinibAC220AC 220AC-220FLT3Ligand for Target Protein for PROTACApoptosisAutophagyCluster of differentiation antigen 135CD135Fms like tyrosine kinase 3Target Protein-binding MoietyoralselectiveAMLacutemyeloidleukemiaFLT3-ITDmutationInhibitorinhibitorinhibit

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    製品名:
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    製品番号:
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