同义名 :	-
	CAS号 :	1257628-77-5
	货号 :	A163539
	分子式 :	C29H27F3N6O
	纯度 :	98%
	分子量 :	532.56
	MDL号 :	MFCD26142930
	存储条件：	Pure form Sealed in dry, 2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性
描述	Bcr-Abl fusion tyrosine kinase is formed because of a reciprocal chromosomal translocation between chromosomes 9 and 22, producing the Philadelphia chromosome. Bcr-Abl is expressed in chronic myeloid leukemia(CML) and a chronic of acute lymphocytic leukemia[3]. GZD824 is an orally bioavailable inhibitor against a broad spectrum of Bcr-Abl mutants including Bcr-AblWT and Bcr-AblT315I with Kd values of 0.32nM and 0.71nM, respectively, and with IC50 values of 0.34nM and 0.68nM, respectively. In vitro, GZD824 potently suppressed proliferation of Bcr-Abl positive human CML cell lines K562 , Ku812, SUP-B15, U-937, MOLT4 and HL-60 with IC50 values of 0.2nM, 0.13nM, 2.5nM, 390.2nM, 26.3nM, and348.9nM, respectively. GZD824 suppressed the activation of Bcr-Abl and downstream Crk1 and STAT5 in a dose-dependent manner in K562 cells. In vivo, oral administration of GZD824 at 5 and 10mg/kg once daily for 14 consecutive days significantly suppressed tumor growth in mice bearing xenografted K562 cells. Oral administration of GZD824 at 1mg/kg once daily for 14 days induced complete tumor regression in mice bearing xenografted Ku812 cells. In addition, treatment of the mice bearing xenografted Ba/F3 cells expressing Bcr-Abl T315I with GZD824 at dose of 20mg/kg once daily via oral administration for 14 days induced almost complete tumor regression[1].
作用机制	GZD824 inhibits the activation of Bcr-Abl by binding to the ATP-binding site of nonphosphorylated(DGF-out) Bcr-Abl[1].

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	1.88mL 0.38mL 0.19mL	9.39mL 1.88mL 0.94mL	18.78mL 3.76mL 1.88mL

参考文献

[1]Ren X, Pan X, Zhang Z, et al. Identification of GZD824 as an orally bioavailable inhibitor that targets phosphorylated and nonphosphorylated breakpoint cluster region-Abelson (Bcr-Abl) kinase and overcomes clinically acquired mutation-induced resistance against imatinib. Journal of Medicinal Chemistry, 2013, 56(3): 879-894 [2]Ye W, Jiang Z, et al. GZD824 suppresses the growth of human B cell precursor acute lymphoblastic leukemia cells by inhibiting the SRC kinase and PI3K/AKT pathways. Oncotarget. 2016 Jul 28;8(50):87002-87015. [3]Skorski T. BCR-ABL1 Kinase: Hunting an Elusive Target with New Weapons. Chemistry & Biology, 2011, 18(11): 1352-1353