Inhibition of hydrogen peroxide-induced necrotic cell death with 3-amino-2-indolylmaleimide derivatives.
Novel analogs of indolylmaleimide derivatives (IM derivatives) were synthesized and tested for cell death-inhibitory activity. 2-(1H-Indol-3-yl)-3-pentylamino-maleimide IM-54 was the most effective cell death inhibitor among the compounds tested. IM-54 inhibited necrotic cell death induced by H2O2, but not apoptotic cell death induced by etoposide. These results indicated that this novel cell death inhibitor is distinct from the well-known caspase inhibitor, Z-VAD, which can block apoptotic cell death, but not necrotic cell death. IM-54 is expected to be a powerful bioprobe for clarifying the unique signaling pathway of necrotic cell death.
Dodo
Kosuke
K
Institute of Multidisciplinary Research for Advanced Materials (IMRAM), Tohoku University, 2-1-1 Katahira, Aoba, Sendai, Miyagi 980-8577, Japan.
Katoh
Miho
M
Shimizu
Tadashi
T
Takahashi
Masahiro
M
Sodeoka
Mikiko
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D018922:HL-60 Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D009336:Necrosis; D016877:Oxidants / Q000494:pharmacology; D011494:Protein Kinases / Q000737:chemistry; D013329:Structure-Activity Relationship
C503757:2-(1H-indol-3-yl)-3-pentylamino-maleimide; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D016877:Oxidants; D005047:Etoposide; D006861:Hydrogen Peroxide; D011494:Protein Kinases