Development of Novel Alkene Oxindole Derivatives As Orally Efficacious AMP-Activated Protein Kinase Activators

doi:10.1021/ml400028q

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	Development of Novel Alkene Oxindole Derivatives As Orally Efficacious AMP-Activated Protein Kinase Activators
	Yu, Li-Fang; Li, Yuan-Yuan; Su, Ming-Bo; Zhang, Mei; Zhang, Wei; Zhang, Li-Na; Pang, Tao; Zhang, Run-Tao; Liu, Bing; Li, Jing-Ya
刊名	ACS MEDICINAL CHEMISTRY LETTERS
	2013-05
卷号	4 期号:5 页码:475-480
关键词	AMPK activator alkene oxindole DIO mouse model insulin sensitivity diabetes
ISSN号	1948-5875
DOI	10.1021/ml400028q
文献子类	Article
英文摘要	Adenosine 5'-monophosphate-activated protein kinase (AMPK) is emerging as a promising drug target for its regulatory function in both glucose and lipid metabolism. Compound PT1 (5) was originally identified from high throughput screening as a small molecule activator of AMPK through the antagonization of the autoinhibition in alpha subunits. In order to enhance its potency at AMPK and bioavailability, structure-activity relationship studies have been performed and resulted in a novel series of AMPK activators based on an alkene oxindole scaffold. Following their evaluation in pharmacological AMPK activation assays, lead compound 24 was identified to possess improved potency as well as favorable pharmacokinetic profile. In the diet-induced obesity (DIO) mouse model, compound 24 was found to improve glucose tolerance and alleviate insulin resistance. The in vitro and in vivo data for these alkene oxindoles warrant further studies for their potential therapeutic medications in metabolic associated diseases.
资助项目	National Natural Science Foundation of China[30725049] ; National Natural Science Foundation of China[81125023] ; National Natural Science Foundation of China[81273566]
WOS关键词	SKELETAL-MUSCLE ; BIOACTIVATION ; METFORMIN ; PATHWAYS ; LEPTIN ; DRUGS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000318892800013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277634]
专题	国家新药筛选中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Nan, Fa-Jun
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Chinese Natl Ctr Drug Screening, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Yu, Li-Fang,Li, Yuan-Yuan,Su, Ming-Bo,et al. Development of Novel Alkene Oxindole Derivatives As Orally Efficacious AMP-Activated Protein Kinase Activators[J]. ACS MEDICINAL CHEMISTRY LETTERS,2013,4(5):475-480.
APA	Yu, Li-Fang.,Li, Yuan-Yuan.,Su, Ming-Bo.,Zhang, Mei.,Zhang, Wei.,...&Nan, Fa-Jun.(2013).Development of Novel Alkene Oxindole Derivatives As Orally Efficacious AMP-Activated Protein Kinase Activators.ACS MEDICINAL CHEMISTRY LETTERS,4(5),475-480.
MLA	Yu, Li-Fang,et al."Development of Novel Alkene Oxindole Derivatives As Orally Efficacious AMP-Activated Protein Kinase Activators".ACS MEDICINAL CHEMISTRY LETTERS 4.5(2013):475-480.