Inhibition of the her2 tyrosine kinase and characterization of a hydrophobic site near the nucleotide binding domain

A series of compounds was prepared to investigate the hydrophobic character of the HER2 receptor tyrosine kinase active site. These bisubstrate analogs contained hydrophobic moieties in place of the polar triphosphate and nucleoside fragments of the natural ATP ligand. Despite these modifications, good affinity was observed as measured by inhibition of receptor autophosphorylation.