1. A Specific Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase
- Author
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Alan J. Kraker, Linda A. Ambroso, David W. Fry, Wilbur R. Leopold, Amy McMichael, Alexander James Bridges, Richard W. Connors, and James M. Nelson
- Subjects
Gene Expression ,Mitosis ,Protein tyrosine phosphatase ,Biology ,Tropomyosin receptor kinase C ,Receptor tyrosine kinase ,Mice ,Tumor Cells, Cultured ,Animals ,Humans ,Phosphorylation ,Platelet-Derived Growth Factor ,Multidisciplinary ,Epidermal Growth Factor ,Autophosphorylation ,3T3 Cells ,Protein-Tyrosine Kinases ,Molecular biology ,ErbB Receptors ,Kinetics ,Cell Transformation, Neoplastic ,ROR1 ,Quinazolines ,Cancer research ,biology.protein ,Tyrosine ,Fibroblast Growth Factor 2 ,Tyrosine kinase ,Platelet-derived growth factor receptor ,Proto-oncogene tyrosine-protein kinase Src - Abstract
A small molecule called PD 153035 inhibited the epidermal growth factor (EGF) receptor tyrosine kinase with a 5-pM inhibition constant. The inhibitor was specific for the EGF receptor tyrosine kinase and inhibited other purified tyrosine kinases only at micromolar or higher concentrations. PD 153035 rapidly suppressed autophosphorylation of the EGF receptor at low nanomolar concentrations in fibroblasts or in human epidermoid carcinoma cells and selectively blocked EGF-mediated cellular processes including mitogenesis, early gene expression, and oncogenic transformation. PD 153035 demonstrates an increase in potency over that of other tyrosine kinase inhibitors of four to five orders of magnitude for inhibition of isolated EGF receptor tyrosine kinase and three to four orders of magnitude for inhibition of cellular phosphorylation.
- Published
- 1994
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