Quizartinib (AC220)
(Synonyms: 奎扎替尼; AC220) 目录号 : GC17615
Quizartinib (AC220)是一种高效的第二代Fms样酪氨酸激酶3（FLT3）抑制剂，对FLT3-ITD和FLT3-WT的IC50值分别为1.1nM和4.2nM。
Cas No.:950769-58-1
Sample solution is provided at 25 µL, 10mM.
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Quizartinib (AC220) is a highly potent second-generation Fms-like tyrosine kinase 3 (FLT3) inhibitor, with IC50 values of 1.1nM and 4.2nM for FLT3-ITD and FLT3-WT, respectively[1]. Quizartinib exhibits significantly higher selectivity for FLT3 than for other kinases such as PDGFRα, PDGFRβ, KIT, RET, and CSF-1R[2]. Quizartinib is primarily used to treat relapsed/refractory acute myeloid leukemia (AML), showing significant efficacy in patients with FLT3-ITD mutations[3]. Quizartinib can inhibit necroptosis by targeting receptor-interacting serine/threonine protein kinase 1 (RIPK1)[4].
In vitro, treatment of FLT3-ITD-mutant acute myeloid leukemia MV4-11 cells with Quizartinib (20nM) for 1h significantly inhibited cell growth and phosphorylation of FLT3 and ERK[5]. Treatment of neonatal rat ventricular myocytes and H9c2 cells with Quizartinib (200nM-20μM) for 72h dose-dependently reduced cell viability and significantly enhanced H2O2-induced cell death and apoptosis[6].
In vivo, oral administration of Quizartinib (1, 10mg/kg/day) for 14 days to mice bearing MV4-11 cell xenografts significantly inhibited tumor growth and reduced the levels of pFLT3, pErk1/2, pSTAT5, and pAkt in tumor cells[7].
References:
[1] Zarrinkar P P, Gunawardane R N, Cramer M D, et al. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML)[J]. Blood, 2009, 114(14): 2984-2992.
[2] Acharya B, Saha D, Armstrong D, et al. FLT3 inhibitors for acute myeloid leukemia: successes, defeats, and emerging paradigms[J]. RSC Medicinal Chemistry, 2022, 13(7): 798-816.
[3] Wander S A, Levis M J, Fathi A T. The evolving role of FLT3 inhibitors in acute myeloid leukemia: quizartinib and beyond[J]. Therapeutic advances in hematology, 2014, 5(3): 65-77.
[4] Aikawa T, Togashi N, Iwanaga K, et al. Quizartinib, a selective FLT3 inhibitor, maintains antileukemic activity in preclinical models of RAS-mediated midostaurin-resistant acute myeloid leukemia cells[J]. Oncotarget, 2020, 11(11): 943.
[5] Li M, Wei J, Zhu G, et al. Quizartinib inhibits necroptosis by targeting receptor‐interacting serine/threonine protein kinase 1[J]. The FASEB Journal, 2023, 37(10): e23178.
[6] Monogiou Belik D, Bernasconi R, Xu L, et al. The Flt3-inhibitor quizartinib augments apoptosis and promotes maladaptive remodeling after myocardial infarction in mice[J]. Apoptosis, 2024, 29(3): 357-371.
[7] Gunawardane R N, Nepomuceno R R, Rooks A M, et al. Transient exposure to quizartinib mediates sustained inhibition of FLT3 signaling while specifically inducing apoptosis in FLT3-activated leukemia cells[J]. Molecular cancer therapeutics, 2013, 12(4): 438-447.
Quizartinib (AC220)是一种高效的第二代Fms样酪氨酸激酶3（FLT3）抑制剂，对FLT3-ITD和FLT3-WT的IC50值分别为1.1nM和4.2nM[1]。Quizartinib对FLT3的选择性远高于PDGFRα、PDGFRβ、KIT、RET和CSF-1R等激酶[2]。Quizartinib主要用于治疗复发/难治性急性髓系白血病（AML），尤其对携带FLT3-ITD突变的患者显示出显著疗效[3]。Quizartinib能够通过靶向受体相互作用丝氨酸/苏氨酸蛋白激酶1（RIPK1）抑制细胞坏死性凋亡[4]。
在体外，Quizartinib（20nM）处理FLT3-ITD突变急性髓系白血病MV4-11细胞1h，显著抑制了细胞生长，抑制了细胞内FLT3和ERK的磷酸化[5]。Quizartinib（200nM-20μM）处理新生大鼠心室肌细胞和H9c2细胞72h，剂量依赖性地降低了细胞的活力，显著增强了H2O2诱导的细胞死亡和凋亡[6]。
在体内，Quizartinib（1, 10mg/kg/day）通过口服治疗MV4-11细胞异种移植小鼠14天，显著抑制了小鼠体内肿瘤生长，降低了肿瘤细胞内pFLT3、pErk1/2、pSTAT5和pAkt的水平[7]。
| Cell experiment [1]: | |
Cell lines | FLT3-ITD MV4-11 cells |
Preparation Method | Cells were treated with Quizartinib or gilteritinib at 20nM for 1h, and then the levels of phosphorylated FLT3 and ERK were measured up to 3h after removal of the inhibitors from the cells. |
Reaction Conditions | 20nM; 1h |
Applications | Quizartinib maintained inhibition of FLT3 phosphorylation and ERK phosphorylation through 3h after removal, while gilteritinib had no significant inhibitory activity starting 1h after removal. |
| Animal experiment [2]: | |
Animal models | Female C.B-17 SCID mice |
Preparation Method | Mice were implanted subcutaneously on day 0 with 5×106 MV4-11 cells in a 50:25:25 mixture of PBS and high/low concentration Matrigel basement membrane matrix. Treatment began when the mean estimated tumor mass for all groups (10 mice per group) reached approximately 250mm3. Quizartinib, formulated in 5% hydroxypropyl-β-cyclodextrin, was administered orally by gavage at 1 or 10mg/kg once daily for 1 or 14 consecutive days. Animals with tumors exceeding 2000mm3 or with severely ulcerated tumors were euthanized, as were those showing obvious signs of distress or a moribund condition. Body weights and tumor measurements were recorded three times weekly. |
Dosage form | 1 or 10mg/kg/day; 1 or 14 days; p.o. |
Applications | Administration of Quizartinib at a dose of 1mg/kg or 10mg/kg daily for 14 consecutive days can significantly inhibit tumor growth. |
References: | |
| Cas No. | 950769-58-1 | SDF | |
| 别名 | 奎扎替尼; AC220 | ||
| 化学名 | 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[4-[6-(2-morpholin-4-ylethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl]urea | ||
| Canonical SMILES | CC(C)(C)C1=CC(=NO1)NC(=O)NC2=CC=C(C=C2)C3=CN4C5=C(C=C(C=C5)OCCN6CCOCC6)SC4=N3 | ||
| 分子式 | C29H32N6O4S | 分子量 | 560.67 |
| 溶解度 | ≥ 28.0335mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7836 mL | 8.9179 mL | 17.8358 mL |
| 5 mM | 356.7 μL | 1.7836 mL | 3.5672 mL |
| 10 mM | 178.4 μL | 891.8 μL | 1.7836 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.50%
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