SH2 domain inhibition: a problem solved?
The past two years have witnessed a number of significant advances in the design 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 context of bone-binding phosphotyrosine bioisostere, has yielded an in vivo active 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 agent.
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ARIAD Pharmaceuticals, Inc., 26 Landsdowne Street, 02139-4234, Cambridge, MA, USA
D008958:Models, Molecular; D011487:Protein Conformation; D018909:src Homology Domains