New inhibitors of SH2-mediated processes

Abstract

This patent discloses a group of compounds that bind with the SH2 domains of a number of different proteins. The compounds contain a nitro-group-substituted tyrosine residue as a phosphotyrosine analogue. These compounds are presented as a solution to the difficulty found when using a highly charged phosphotyrosine residue in a pharmaceutical preparation. The binding affinities of a selection of the claimed compounds were established using a competition assay and are reported as the concentration required to reduce binding by 50%. The compounds were tested for binding with the SH2 domains of proteins p60src, pp72syk and pp70zap. The most potent binding measured in this series was 11 μM. Binding was consistently tightest with pp72syk.

• phosphotyrosine mimic
• SH2 domain
• signal transduction