Accession Number : ADA338938

Title :   Study of Inhibitors of Neu and Related Tyrosine-Specific Protein Kinases: Implications for the Treatment of Breast Cancer

Descriptive Note : Annual rept. 30 Sep 96-31 Aug 97

Corporate Author : STATE UNIV OF NEW YORK AT BUFFALO AMHERST

Personal Author(s) : Edelman, Arthur

PDF Url : ADA338938

Report Date : SEP 1997

Pagination or Media Count : 17

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.

Descriptors :   *INHIBITORS, *TYROSINE, *PHOSPHORUS TRANSFERASES, *BREAST CANCER, PEPTIDES, PROTEINS, SUBSTRATES, INHIBITION, CELLS(BIOLOGY), GROWTH(PHYSIOLOGY), PHENYLALANINE, COENZYMES.

Subject Categories : Biochemistry
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE