SH2 domain inhibition: a problem solved?

The past two years have witnessed a number of significant advances in the d esign of SH2 inhibitors of both Src and Grb2. For Src, several non-peptide templates have been developed with high affinity, and one case, in the cont ext of bone-binding phosphotyrosine bioisostere, has yielded an in vivo act ive antiresorptive agent. Similarly, high-affinity Grb2 SH2 inhibitors with novel phosphotyrosine replacements have now been reported that demonstrate , for the first time, cellular activities consistent with an anticancer age nt.