title: A novel necroptosis inhibitor-necrostatin-21 and its SAR study.
abstract: An initial structure-activity relationship study of the novel necroptosis inhibitor Nec-21 was described. Any changes of the tetracyclic scaffold were detrimental for the activity. Introduction of a substituent to 7 or 8 position (e.g., cyano or methoxy group, respectively), would increase the activity. The 7 and 8-position disubstituted compound 17 b was 35-fold as potent as the lead, while EC50 reached 14 nM.
authors.affiliation: State Key Laboratory of Bio-organic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Cai
authors.forename: Junying
authors.initials: J
authors.lastname: Yuan
authors.forename: Chengye
authors.initials: C
authors.lastname: Yuan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002227:Carbazoles / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D009336:Necrosis / Q000188:drug therapy*; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D002227:Carbazoles; D011720:Pyrazoles
keywords: Inhibitor; JNK3; Nec-21; Necroptosis; RIP1; SAR study