Abstract
The first direct activator of BAX, a pro-apoptotic member of the BCL-2 family, has been recently identified. Herein, a structure-based lead optimization turned out into a small series of analogues, where 8 is the most potent compound published so far. 8 was used as pharmacological tool to ascertain, for the first time, the anticancer potential of BAX direct activators and the obtained results would suggest that BAX direct activators are potential future anticancer drugs rather than venoms.
Publication types
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Evaluation Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Cell Survival / drug effects
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Cells, Cultured
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Drug Screening Assays, Antitumor*
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Female
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Fluorescent Antibody Technique
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Humans
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Hydrazones / chemistry*
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Hydrazones / pharmacology*
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Immunoblotting
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Immunoprecipitation
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Jurkat Cells
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mitochondria / drug effects
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Mitochondria / metabolism
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Models, Molecular
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Pyrazoles / chemistry*
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Pyrazoles / pharmacology*
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Structure-Activity Relationship
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bcl-2-Associated X Protein / antagonists & inhibitors*
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bcl-2-Associated X Protein / physiology
Substances
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1-(4'-(dimethylamino)-5-hydroxy-(1,1'-biphenyl)-3-yl)-4-(2-(2-ethoxyphenyl)hydrazono)-3-methyl-1H-pyrazol-5(4H)-one
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Antineoplastic Agents
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Hydrazones
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Pyrazoles
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bcl-2-Associated X Protein