Quizartinib

立即咨询

Quizartinib

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

950769-58-1

包装与价格：

包装	价格(元)
10 mM * 1 mL in DMSO	电议
5mg	电议
10mg	电议
50mg	电议
100mg	电议
200mg	电议
500mg	电议
1 g	电议
5 g	电议

产品名称

奎扎替尼
AC220

产品介绍

Quizartinib (AC220) 是一种具有口服活性的、高选择性的，有效的第二代 Ⅱ 型 FLT3(type II FLT3)酪氨酸激酶抑制剂，K_d值为 1.6 nM。Quizartinib 抑制 Wt FLT3 和突变型 FLT3-ITD 自磷酸化，IC₅₀分别为 4.1 nM 和 1.1 nM。Quizartinib 可以通过优化的 linker 与 VHL 配体连接，从而形成 PROTAC Flt3 降解剂。Quizartinib 诱导细胞凋亡 (apoptosis)。

生物活性

Quizartinib (AC220) is an orally active, highly selective and potent second-generation type IIFLT3tyrosine kinaseinhibitor, with aK_dof 1.6 nM. Quizartinib inhibits wild-typeFLT3and 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 aPROTACFLT3 degrader. Quizartinib inducesapoptosis^[1].

IC₅₀& Target

Kd: 1.6±0.7 nM (Flt3)^[1]

体外研究
(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 IC₅₀of 4.2±0.3 nM and 1.1±0.1 nM, respectively. Quizartinib inhibits MV4-11 and A375 cells with IC₅₀of 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].

体内研究
(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].

Clinical Trial

分子量

560.67

性状

Solid

Formula

C₂₉H₃₂N₆O₄S

CAS 号

950769-58-1

中文名称

奎扎替尼

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

溶解性数据

In Vitro:

DMSO : ≥ 33 mg/mL(58.86 mM)

*"≥" means soluble, but saturation unknown.

配制储备液

浓度溶剂体积质量

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

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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

In Vivo:

1.
Quizartinib (AC220) is prepared in vehicle (22% hydroxypropyl-β-cyclodextrin in sterile water)^[2].