Abstract
Phosphoinositide 3-kinase (PI3K) is an important target for cancer chemotherapy due to the deregulation of its signaling pathway in a wide spectrum of human tumors. Wortmannin and its analogues are potent PI3K inhibitors whose therapeutic use has been impeded by inherent defects such as instability and toxicity. Pegylation of wortmannin and 17-hydroxywortmannin gives rise to conjugates with improved properties, including a higher therapeutic index. Pegylated 17-hydroxywortmannin (8, PWT-458) has been selected for further development.
MeSH terms
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Androstadienes / chemical synthesis*
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Androstadienes / chemistry
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Androstadienes / pharmacology
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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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Humans
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Mice
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Mice, Nude
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Phosphoinositide-3 Kinase Inhibitors*
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Polyethylene Glycols / chemical synthesis
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Polyethylene Glycols / chemistry*
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Polyethylene Glycols / pharmacology
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Structure-Activity Relationship
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Wortmannin
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Xenograft Model Antitumor Assays
Substances
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Androstadienes
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Antineoplastic Agents
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Phosphoinositide-3 Kinase Inhibitors
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pegylated 17-hydroxywortmannin
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17-hydroxywortmannin
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Polyethylene Glycols
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Wortmannin