Abstract
Epidermal growth factor receptor (EGF-R), a transmembrane glycoprotein that mediates the mitogenic response of cells to epidermal growth factor, is highly expressed on malignant human bladder cancer cells. The 4,5-dianilinophthalimides represent a novel class of inhibitors of the EGF-R family of tyrosine kinase with selectivity at the enzymatic and cellular levels. Two compounds of this class, CGP 54211 and CGP 53353, inhibited tyrosine kinase activity of the EGF-R in five different human transitional cell carcinoma lines. The compounds also produced cytostasis in vitro. Highly metastatic human 253J B-V cells were implanted in the bladder wall of nude mice. The daily oral administration of CGP 54211 inhibited the level of EGF-R phosphorylation in this tumor; necrosis and inhibition of tumor growth paralleled this inhibition.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Triphosphate / metabolism
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Administration, Oral
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Animals
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Carcinoma, Transitional Cell / drug therapy*
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Carcinoma, Transitional Cell / enzymology
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Carcinoma, Transitional Cell / pathology
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Cell Division / drug effects
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / therapeutic use*
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / metabolism
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Humans
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Immunohistochemistry
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasm Transplantation
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Phthalimides / pharmacology
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Phthalimides / therapeutic use*
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Tumor Cells, Cultured
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Urinary Bladder Neoplasms / drug therapy*
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Urinary Bladder Neoplasms / enzymology
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Urinary Bladder Neoplasms / pathology
Substances
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Enzyme Inhibitors
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Phthalimides
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Adenosine Triphosphate
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ErbB Receptors
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4,5-dianilinophthalimide