产品说明书

Nilotinib

Print

	同义名 :	尼罗替尼 (AMN-107) ;AMN107
	CAS号 :	641571-10-0
	货号 :	A448494
	分子式 :	C₂₈H₂₂F₃N₇O
	纯度 :	98%
	分子量 :	529.52
	MDL号 :	MFCD09833716
	存储条件：	粉末 Sealed in dry,Store in freezer, under -20°C 液体 -20°C:3-6个月-80°C:12个月
	溶解度 :	DMSO: 12 mg/mL(22.66 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
	动物实验配方：	IP 2% DMSO+water 0.2 mg/mL clear PO 0.5% CMC-Na 40 mg/mL suspension

生物活性
靶点	Bcr-Abl Bcr-Abl, IC50:<30 nM
描述	The oncogenic tyrosine kinase Bcr-Abl plays a central role in the pathogenesis of chronic myelogenous leukemia, thus makes it as the therapy drug target. However, it is demonstrated that the mutations of Bcr-Abl kinase have been the most common mechanism of drug resistance, such as imatinib. Nilotinib is a potent and selective Bcr-Abl inhibitor with IC50 values of 15nM, as well as IC50 values ranging in 9-400nM for different Abl mutations except the T315l mutation (measured by in vitro kinase assays)^[1]. Though Nilotinib was structured based on imatinib, in vitro study showed that Nilotinib showed differential sensitivity of Abl point mutations with imatinib^[1]^[2]. Nilotinib inhibited proliferation of Ba/F3 cells expressing G250E, E255K(V), F317L, M351T, F486S, M244V, L248R, Q252H, Y253H, E255K, E279K, E282D, V289S, and L348M Bcr-Abl mutants at concentration<1μM, as well as tyrosine autophosphorylation of the E255K, E255V, F317L, M351T and F486S Bcr-Abl mutants with mean IC50 values of 150, 246, 41, 31 and 43 nM, respectively. Activity against PDGFR and c-Kit by Nilotinib also can be observed at concentration<200nM. Oral dose of 75mg/kg Nilotinib prolonged survival and decreased tumor burden in an imatinib-resistant Bcr-Abl mutant BMT model^[2].
作用机制	Nilotinib was found to bind to the inactive conformation of Abl as observed for imatinib, resulting differential sensitivity of Abl point mutations by Nilotinib.^[2]

细胞研究
细胞系	浓度	检测类型	检测时间	活动说明	数据源
697		Growth Inhibition Assay		IC50=11.2101 μM	SANGER
769-P		Growth Inhibition Assay		IC50=19.6335 μM	SANGER
A101D		Growth Inhibition Assay		IC50=10.8923 μM	SANGER

临床研究
NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
NCT00785785	-		Completed	-	-
NCT01220648	Chronic Myeloid Leukemia	Phase 1	Completed	-	Germany ... 展开 >> Novartis Investigative Site Leipzig, Germany, 04103 收起 <<
NCT01806571	Untreated Adult Acute Myeloid ... 展开 >>Leukemia 收起 <<	Phase 2	Active, not recruiting	April 18, 2020	United States, Arizona ... 展开 >> Mayo Clinic in Arizona Scottsdale, Arizona, United States, 85259 United States, Minnesota Mayo Clinic Rochester, Minnesota, United States, 55905 收起 <<

实验方案

1mg

5mg

10mg

1 mM

5 mM

10 mM

1.89mL

0.38mL

0.19mL

9.44mL

1.89mL

0.94mL

18.89mL

3.78mL

1.89mL

参考文献

[1]O'Hare T, Walters DK, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 2005 Jun 1;65(11):4500-5.

[2]Weisberg E, Manley PW, et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell. 2005 Feb;7(2):129-41.

✕

靶点

靶点	数值

Bcr-Abl

Bcr-Abl, IC50:<30 nM