Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents, Phytogenic / pharmacology
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Apoptosis / drug effects
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Cell Death / drug effects*
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Enzyme Inhibitors / pharmacology
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Etoposide / pharmacology
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HL-60 Cells / drug effects
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HL-60 Cells / pathology
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Humans
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Hydrogen Peroxide / pharmacology
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Indoles / chemical synthesis
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Indoles / chemistry*
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Indoles / pharmacology*
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Maleimides / chemical synthesis
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Maleimides / chemistry*
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Maleimides / pharmacology*
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Molecular Structure
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Necrosis
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Oxidants / pharmacology
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Protein Kinases / chemistry
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Structure-Activity Relationship
Substances
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2-(1H-indol-3-yl)-3-pentylamino-maleimide
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Antineoplastic Agents
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Antineoplastic Agents, Phytogenic
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Enzyme Inhibitors
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Indoles
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Maleimides
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Oxidants
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Etoposide
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Hydrogen Peroxide
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Protein Kinases