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 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.
Cody
W L
WL
Departments of Chemistry and Cardiovascular Therapeutics, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan 48105, USA. Wayne.Cody@wl.com
Lin
Z
Z
Panek
R L
RL
Rose
D W
DW
Rubin
J R
JR
D000595:Amino Acid Sequence; D000818:Animals; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry; D018909:src Homology Domains / Q000187:drug effects*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry
D004791:Enzyme Inhibitors; D011505:Protein-Tyrosine Kinases; D019061:src-Family Kinases