Signal transducer and activator of transcription (Stat3) is constitutively active in several cancer types and it participates in the increased transcription of cell cycling, survival, and angiogenesis genes. Therefore Stat3 is a target for anti-cancer drug design [1]. Compounds targeted to the SH2 domain of Stat3 would uncouple this protein from its aberrant activity by preventing recruitment to receptors, blocking reciprocal pTyr-SH2 domain dimerization, translocation to the nucleus and DNA binding, thus preventing transcription of the cell-cycling, survival, and angiogenesis genes. To date there are no crystal or NMR structures of high affinity phosphopeptides complexed with the SH2 domain of Stat3 to aid in inhibitor design.
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