Progress in the Development of Inhibitors of SH2 Domains

Authors: Cody, W.L.; Lin, Z.; Panek, R.L.; Rose, D.W.; Rubin, J.R.

Source: Current Pharmaceutical Design, Volume 6, Number 1, 1 January 2000 , pp. 59-98(40)

Publisher: Bentham Science Publishers

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Abstract:

SH2 domains are discrete structural motifs common to a variety of critical intracellular signaling proteins. Inhibitors of specific SH2 domains have become important therapeutic targets in the treatment and/or prevention of restenosis, cancers (including small cell lung), cardiovascular disease, osteoporosis, apoptosis among others. Considering the social and economic impact of these diseases significant attention has been focused on the development of potent and selective inhibitors of specific SH2 domains. In particular, 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 development of inhibitors for these specific SH2 domains and evaluate potential future targets.

Keywords: inhibitors; SH2 Domains; signaling proteins; intracellular; restenosis; cancer; small cell lung; cardiovascular disease; Lck; apoptosis; osteporosis; Src PI3 kinase Grb2; receptor; tyrosine kinases RTK; Fgr; Yrk; Fyn; HcK; Blk; mechansims; platelet derived growth factor PDGF; hepatovyte; fibroblast growth factor FGF; epidermal; focal adhesion kinase; mitogen activated protein kinase; FAK; Cortactin