Structure-activity relationship analysis of a novel necroptosis inhibitor, Necrostatin-5.
Necrostatin-5 (Nec-5) is a novel potent small-molecule inhibitor of necroptosis structurally distinct from previously described Necrostatin-1 (Nec-1), and therefore, represents a new direction for the inhibition of this cellular caspase-independent necrotic cell death mechanism. Here, we describe a series of structural modifications of Nec-5 and the structure-activity relationship (SAR) of Nec-5 series in inhibiting necroptosis.
Wang
Ke
K
State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
Li
Jinfeng
J
Degterev
Alexei
A
Hsu
Emily
E
Yuan
Junying
J
Yuan
Chengye
C
D017209:Apoptosis / Q000187:drug effects*; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D009336:Necrosis / Q000188:drug therapy*; D009570:Nitriles / Q000737:chemistry* / Q000494:pharmacology; D011744:Pyrimidinones / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000737:chemistry / Q000494:pharmacology*
D006575:Heterocyclic Compounds, 3-Ring; C519552:Necrostatin-5; D009570:Nitriles; D011744:Pyrimidinones; D013440:Sulfides