Identification of new dual FABP4/5 inhibitors based on a naphthalene-1-sulfonamide FABP4 inhibitor

doi:10.1016/j.bmc.2019.07.031

	Identification of new dual FABP4/5 inhibitors based on a naphthalene-1-sulfonamide FABP4 inhibitor
	He, Yulong 2; Dou, Huixia 1,3; Gao, Dingding 2,4; Wang, Ting 3; Zhang, Mingming 2; Wang, Heyao 3; Li, Yingxia 2
刊名	BIOORGANIC & MEDICINAL CHEMISTRY
	2019-10-01
卷号	27 期号:19 页码:16
关键词	Dual FABP4/5 inhibitor Structure-based design Lipolysis inhibition Anti-inflammatory effects
ISSN号	0968-0896
DOI	10.1016/j.bmc.2019.07.031
通讯作者	Zhang, Mingming(10111030005@fudan.edu.cn) ; Wang, Heyao(hywang@simm.ac.cn) ; Li, Yingxia(liyx417@fudan.edu.cn)
英文摘要	Fatty acid binding protein 4 (FABP4) and fatty acid binding protein 5 (FABP5) are mainly expressed in adipocytes and/or macrophages and play essential roles in energy metabolism and inflammation. When FABP4 function is diminished, FABP5 expression is highly increased possibly as a functional compensation. Dual FABP4/5 inhibitors are expected to provide beneficial synergistic effect on treating diabetes, atherosclerosis, and inflammation-related diseases. Starting from our previously reported selective FABP4 inhibitor 8, structural biology information was used to modulate the selectivity profile and to design potent dual FABP4/5 inhibitors with good selectivity against FABP3. Two compounds A16 and B8 were identified to show inhibitory activities against both FABP4/5 and good selectivity over FABP3, which could also reduce the level of forskolin-stimulated lipolysis in mature 3T3-L1 adipocytes. Compared with compound 8, these two compounds exhibited better anti-inflammatory effects in lipopolysaccharide-stimulated RAW264.7 murine macrophages, with decreased levels of pro-inflammatory cytokines TNF alpha and MCP-1 and apparently inhibited IKK/NF-kappa B pathway.
资助项目	National Science and Technology Major Project of China[2018ZX09711002] ; Shanghai Science and Technology Support Project[18431900400] ; State Key Laboratory of Drug Research[SIMM1803KF-05] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040336] ; National Natural Science Foundation of China[81473262] ; National Natural Science Foundation of China[81773791] ; China Postdoctoral Science Foundation[2018M642064]
WOS关键词	ACID-BINDING PROTEIN ; METABOLIC-RESPONSES ; AP2 ; EXPRESSION ; OBESITY ; DEFICIENT ; APOPTOSIS ; INSIGHTS ; POTENT ; GENE
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000484396400002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/288740]
专题	中国科学院上海药物研究所
通讯作者	Zhang, Mingming; Wang, Heyao; Li, Yingxia
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Shanghai Univ Tradit Chinese Med, Innovat Res Inst Tradit Chinese Med IRI, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	He, Yulong,Dou, Huixia,Gao, Dingding,et al. Identification of new dual FABP4/5 inhibitors based on a naphthalene-1-sulfonamide FABP4 inhibitor[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2019,27(19):16.
APA	He, Yulong.,Dou, Huixia.,Gao, Dingding.,Wang, Ting.,Zhang, Mingming.,...&Li, Yingxia.(2019).Identification of new dual FABP4/5 inhibitors based on a naphthalene-1-sulfonamide FABP4 inhibitor.BIOORGANIC & MEDICINAL CHEMISTRY,27(19),16.
MLA	He, Yulong,et al."Identification of new dual FABP4/5 inhibitors based on a naphthalene-1-sulfonamide FABP4 inhibitor".BIOORGANIC & MEDICINAL CHEMISTRY 27.19(2019):16.