Progress in the development of inhibitors of SH2 domains

SH2 domains are discrete structural motifs common to a variety of critical intracellular signaling proteins. Inhibitors of specific SH2 domains have b ecome important therapeutic targets in the treatment and/or prevention of r estenosis, cancers (including small cell lung), cardiovascular disease, ost eoporosis, apoptosis among others. Considering the social and economic impa ct of these diseases significant attention has been focused on the developm ent of potent and selective inhibitors of specific SH2 domains. In particul ar, considerable research has been performed on Src, PI 3-kinase, Grb2 and more recently, Lck. In this review, we will focus on progress in the develo pment of inhibitors for these specific SH2 domains and evaluate potential f uture targets.