Synthesis and structure-activity relationship studies of LLY-507 analogues as SMYD2 inhibitors

doi:10.1016/j.bmcl.2020.127598

	Synthesis and structure-activity relationship studies of LLY-507 analogues as SMYD2 inhibitors
	Zhang, Bin 1; Liao, Liping 2,3; Wu, Fan 1; Zhang, Fengcai 2,3; Sun, Zhongya 2,3; Chen, Haijun 1; Luo, Cheng 2,3
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2020-11-15
卷号	30 期号:22 页码:5
关键词	SMYD2 inhibitors Thermal shift assay Structure-activity relationships
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2020.127598
通讯作者	Chen, Haijun(chenhaij@gmail.com)
英文摘要	SET and MYND domain-containing protein 2 (SMYD2), a lysine methyltransferase, is reported to catalyze the methylation of lysine residues on histone and non-histone proteins. As a potential target for cancer therapy, there are several SMYD2 inhibitors are reported, LLY-507 as a cell-active inhibitor exhibits submicromolar potency against SMYD2 in several cancer cell lines. To know which structural fragment of LLY-507 is suitable for chemical modification, three sites are chosen for structure-activity relationship studies (SARs). Among our focused library, compounds 43 and 44 with amide link on site C showed reasonably improved potency indicating that modification on this fragment is more flexible and introduction of electrophilic warheads in this position might provide lysine-targeting covalent inhibitors for SMYD2.
资助项目	Natural Science Foundation of Fujian Province[2019J01202] ; Natural Science Foundation of China[81625022] ; Natural Science Foundation of China[91853205] ; Natural Science Foundation of China[81821005] ; K. C. Wong Education Foundation
WOS关键词	METHYLTRANSFERASE SMYD2 ; LYSINE ; DISCOVERY ; METHYLATION ; INSIGHTS ; FAMILY
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000594726800001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296254]
专题	中国科学院上海药物研究所
通讯作者	Chen, Haijun
作者单位	1.Fuzhou Univ, Key Lab Mol Synth & Funct Discovery, Coll Chem, Fujian Prov Univ, Fuzhou 350116, Fujian, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Bin,Liao, Liping,Wu, Fan,et al. Synthesis and structure-activity relationship studies of LLY-507 analogues as SMYD2 inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2020,30(22):5.
APA	Zhang, Bin.,Liao, Liping.,Wu, Fan.,Zhang, Fengcai.,Sun, Zhongya.,...&Luo, Cheng.(2020).Synthesis and structure-activity relationship studies of LLY-507 analogues as SMYD2 inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,30(22),5.
MLA	Zhang, Bin,et al."Synthesis and structure-activity relationship studies of LLY-507 analogues as SMYD2 inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 30.22(2020):5.