Abstract
The prominent role of IAPs in controlling cell death and their overexpression in a variety of cancers has prompted the development of IAP antagonists as potential antitumor therapies. We describe the identification of a series of heterodimeric antagonists with highly potent antiproliferative activities in cIAP- and XIAP-dependent cell lines. Compounds 15 and 17 further demonstrate curative efficacy in human melanoma and lung cancer xenograft models and are promising candidates for advanced studies.
MeSH terms
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Animals
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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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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Discovery*
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Drug Screening Assays, Antitumor
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Humans
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Inhibitor of Apoptosis Proteins / antagonists & inhibitors*
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Mice
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Molecular Structure
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Neoplasms, Experimental / drug therapy*
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Neoplasms, Experimental / pathology
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Proline / chemical synthesis
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Proline / chemistry
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Proline / pharmacology*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Inhibitor of Apoptosis Proteins
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Proline