Metabolic research of domestically developed small molecule tyrosine kinase inhibitors

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 上海药物代谢研究中心

	Metabolic research of domestically developed small molecule tyrosine kinase inhibitors
	Jiang Jinfang; Chen Xiaoyan; Zhong Dafang
刊名	Acta Pharmaceutica Sinica
	2016
卷号	51 期号:2 页码:248-256
关键词	tyrosine kinase inhibitor in vivo metabolism metabolic approach
ISSN号	0513-4870
其他题名	我国研发的小分子酪氨酸激酶抑制剂的药物代谢研究
文献子类	Review
英文摘要	Drug metabolism research plays an essential role in drug discovery and development. Great efforts have been made domestically to be line with the international standardized research on drug metabolism. In this article, we will review new-generation of tyrosine kinase inhibitors (TKIs), these TKIs include icotinib, apatinib, famitinib, flumatinb, allitinib, fruquintinib, and selatinib, among which icotinib and apatinib have been approved by China food and drug administration (CFDA) to reach the market, while others are in clinical trials. For these TKIs, the structural modified sites are active metabolic centers and CYP3A4 is identified as the primary metabolic enzyme. Considering the active intermediates, the crown ether ring of icotinib is oxidated to open to form an aldehyde; the indolylidene ring of famitinib is oxidated followed by rearrangement to form a quinoneimine; the alpha, beta-unsaturated carbonyl group of allitinib is oxidated to form an epoxide, these intermediates are capable of covalently binding biomolecules and generating toxicity. In addition, human 14C radioactive trials of most of these TKIs have not been conducted, and the data of drug-drug interactions in clinic are also absent, which indicate our deficiency compared to the international regular approaches in metabolic research.
资助项目	重大新药创制科技重大专项[00000000] ; 中国科学院上海药物研究所新药研究国家重点实验室项目[00000000]
WOS研究方向	Pharmacology & Pharmacy (provided by Clarivate Analytics)
语种	中文
CSCD记录号	CSCD:5802457
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/269236]
专题	上海药物代谢研究中心
通讯作者	Zhong Dafang
作者单位	Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
推荐引用方式 GB/T 7714	Jiang Jinfang,Chen Xiaoyan,Zhong Dafang. Metabolic research of domestically developed small molecule tyrosine kinase inhibitors[J]. Acta Pharmaceutica Sinica,2016,51(2):248-256.
APA	Jiang Jinfang,Chen Xiaoyan,&Zhong Dafang.(2016).Metabolic research of domestically developed small molecule tyrosine kinase inhibitors.Acta Pharmaceutica Sinica,51(2),248-256.
MLA	Jiang Jinfang,et al."Metabolic research of domestically developed small molecule tyrosine kinase inhibitors".Acta Pharmaceutica Sinica 51.2(2016):248-256.