Study of Inhibitors of Neu and Related Tyrosine-Specific Protein Kinases: Implications for the Treatment of Breast Cancer
Abstract
The vast majority of potent tyrosine kinase-specific inhibitors described to date are competitive with ATP. Although these species tend to exhibit impressive Ki values, their effectiveness under physiological conditions is markedly impaired due to high intracellular concentrations of ATP. Peptide based inhibitors that are competitive with protein/peptide substrate have been described for various tyrosine kinases, however these nonphosphorylatable phenylalanine containing inhibitors typically display poor inhibitory profiles. We have found that L-Dopa serves as a powerful nonphosphorylatable tyrosine mimetic. In addition, we have identified several promising leads in the creation of nonpeptidic inhibitors of tyrosine kinases. Since these species are not directed to the ATP binding region, they do not suffer from the disadvantages associated with ATP analogs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1997
- Accession Number
- ADA338938
Entities
People
- Arthur Edelman
Organizations
- University at Buffalo