Quizartinib (AC220)

製品コードS1526 バッチS152602

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 33 mg/mL (58.85 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）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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. This compound 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. It 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. This chemical 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. This compound 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 this chemical 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. It 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 this compound 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 incubation with this chemical. 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 this compound 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 this compound 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

参考

  • https://pubmed.ncbi.nlm.nih.gov/19654408/

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：

High mtDNA content identifies oxidative phosphorylation-driven acute myeloid leukemias and represents a therapeutic vulnerability [ Signal Transduct Target Ther, 2025, 10(1):222] PubMed: 40653487
ADH5/ALDH2 dehydrogenases and DNA polymerase theta protect normal and malignant hematopoietic cells from formaldehyde challenge: therapeutic implications [ Leukemia, 2025, 39(9):2152-2162] PubMed: 40640557
Dual targeting of CDK6 and LSD1 is synergistic and overcomes differentiation blockade in AML [ EMBO Mol Med, 2025, 10.1038/s44321-025-00296-2] PubMed: 40883610
Chaperone-mediated autophagy regulates the metastatic state of mesenchymal tumors [ EMBO Mol Med, 2025, 17(4):747-774] PubMed: 40055574
FLT3 inhibitors induce p53 instability, driven by STAT5/MDM2/p53 competitive interactions in acute myeloid leukemia [ Cancer Lett, 2025, 611:217446] PubMed: 39756787
Inhibition of NLRP3 enhances pro-apoptotic effects of FLT3 inhibition in AML [ Cell Commun Signal, 2025, 23(1):53] PubMed: 39875995
FLT3-ITD promotes immune checkpoint CD80 via ROS elevation in acute myeloid leukemia [ Front Immunol, 2025, 16:1577313] PubMed: 40746567
Conventional type 1 dendritic cells in the lymph nodes aggravate neuroinflammation after spinal cord injury by promoting CD8+ T cell expansion [ Mol Med, 2025, 31(1):37] PubMed: 39901071
Anti-Tumor Effects of Gilteritinib on FLT3 Mutations: Insights into Resistance Mechanisms in Ba/F3 Cell Models [ Onco Targets Ther, 2025, 18:489-501] PubMed: 40196870
Multi-selective RAS(ON) Inhibition Targets Oncogenic RAS Mutations and Overcomes RAS/MAPK-Mediated Resistance to FLT3 and BCL2 Inhibitors in Acute Myeloid Leukemia [ bioRxiv, 2025, 2025.06.10.658786] PubMed: 40661530

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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