Quizartinib (AC220)

製品コードS1526 バッチS152604

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C29H32N6O4S
分子量 560.67 CAS No. 950769-58-1
Solubility (25°C)* 体外 DMSO 100 mg/mL (178.35 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
0.5mg/ml Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Quizartinib (AC220) is a second-generation FLT3 inhibitor for Flt3(ITD/WT) with IC50 of 1.1 nM/4.2 nM in MV4-11 and RS4;11 cells, respectively, 10-fold more selective for Flt3 than KIT, PDGFRα, PDGFRβ, RET, and CSF-1R. Quizartinib (AC220) induces apoptosis of tumor cells. Phase 3.
in vitro AC220, a unique, potent and selective inhibitor of FLT3, has high affinity for FLT3 with a Kd value of 1.6 nM. AC220 inhibits the autophosphorylation of FLT3 in the human leukemia cell lines MV4-11 which harbor a homozygous FLT3-ITD mutation and is FLT3 dependent, and RS4;11 which expresses wild-type FLT3 with IC50 values of 1.1 nM and 4.2 nM, respectively. AC220 is the most potent cellular FLT3-ITD inhibitor, leading to the most significant inhibition of MV4-11 cell proliferation with IC50 of 0.56 nM compared to all other FLT3 inhibitors whose IC50 values range from 0.87 nM to 64 nM. AC220 has no inhibitory activity against the proliferation of A375 cells which harbor an activating mutation in BRAF and are not FLT3 dependent, indicating a large window between FLT3 inhibition and general cytotoxic effects. [1]
in vivo Oral administration of AC220 (10 mg/kg) induces time-dependent inhibition of FLT3 autophosphorylation in the FLT3-ITD–dependent MV4-11 tumor xenograft mouse model; the inhibition being 90% at 2 hours and 40% at 24 hours. AC220 significantly extends survival in a mouse model of FLT3-ITD AML with doses as low as 1 mg/kg given orally once a day. Treatment with AC220 at 10 mg/kg for 28 days results in rapid and complete regression of tumors in all mice with no tumor regrowth during the 60-day posttreatment period. AC220 displays more significant efficacy compared to sunitinib treatment which causes tumors to shrink slowly and resume growth immediately upon discontinuation of treatment in all but one of the mice. [1]
特徴 The most potent cellular FLT3-ITD inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ Inhibition of FLT3 autophosphorylation
To measure inhibition of FLT3 autophosphorylation, MV4-11 or RS4;11 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 different concentrations of AC220 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 AC220 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. The concentration of AC220 that inhibits FLT3-ITD or TLT3-WT autophosphorylation by 50% represents IC50 value
細胞アッセイ 細胞株 MV4-11 and RS4;11 cells
濃度 Dissolved in DMSO, final concentration ~20 μM
反応時間 72 hours
実験の流れ Cells are cultured overnight in low serum media (0.5% FBS), seeded in a 96-well plate at 40 000 cells per well and exposed to AC220 for 72 hours at 37 °C. Cell viability is measured using the Cell Titer-Blue Cell Viability Assa
動物実験 動物モデル Female NU/NU or severe combined immunodeficient mice implanted with MV4-11 cells
投薬量 ~10 mg/kg
投与方法 Oral gavage

カスタマーフィードバック

Data from [Data independently produced by Mol Cancer Ther, 2014, 13(10), 2315-27]

Data from [Data independently produced by PLoS One, 2013, 8(8), e71266]

, , Leuk Lymphoma, 2017, 58(10):2426-2438

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Targeting FLT3-TAZ signaling to suppress drug resistance in blast phase chronic myeloid leukemia [ Mol Cancer, 2023, 10.1186/s12943-023-01837-4] PubMed: 37932786
Targeting FLT3 with a new-generation antibody-drug conjugate in combination with kinase inhibitors for treatment of AML [ Blood, 2023, 141(9):1023-1035] PubMed: 35981498
A combinatorial therapeutic approach to enhance FLT3-ITD AML treatment [ Cell Rep Med, 2023, 10.1016/j.xcrm.2023.101286] PubMed: 37951217
Structural and functional analyses of a germline KRAS T50I mutation provide insights into Raf activation [ JCI Insight, 2023, 8(17)e168445] PubMed: 37681415
Structural and functional analyses of a germline KRAS T50I mutation provide insights into Raf activation [ JCI Insight, 2023, 8(17)e168445] PubMed: 37681415
The Flt3-inhibitor quizartinib augments apoptosis and promotes maladaptive remodeling after myocardial infarction in mice [ Apoptosis, 2023, 10.1007/s10495-023-01911-8] PubMed: 37945814
The GSK3β/Mcl-1 axis is regulated by both FLT3-ITD and Axl and determines the apoptosis induction abilities of FLT3-ITD inhibitors [ Cell Death Discov, 2023, 9(1):44] PubMed: 36739272
The multi-kinase inhibitor CG-806 exerts anti-cancer activity against acute myeloid leukemia by co-targeting FLT3, BTK, and Aurora kinases [ Res Sq, 2023, rs.3.rs-2570204] PubMed: 36865133
A truncated derivative of FGFR1 kinase cooperates with FLT3 and KIT to transform hematopoietic stem cells in syndromic and de novo AML [ Mol Cancer, 2022, 21(1):156] PubMed: 35906694
TARGETING FLT3 BY NEW-GENERATION ANTIBODY-DRUG-CONJUGATE IN COMBINATION WITH KINASE INHIBITORS FOR TREATMENT OF AML [ Blood, 2022, blood.2021015246] PubMed: 35981498

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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