Active phosphatase scaffolds while bypassing a primary assay that would entail a highthroughput biochemical screening of compounds in vitro. Coupling this effort with biochemical assays, we prioritized compound 36 as a lead molecule. Our future studies will include structure-based refinement of this scaffold in order to develop 123653-11-2 cost selective inhibitors of PTPs. In this approach, we will characterize the activity of compound 36 against related PTPs and following, use molecular docking and structural analyses of these counter-targets to identify chemical modifications that promote selectivity for PTPs. Wnt family genes encode highly purchase 6078-17-7 conserved secreted glycoproteins, which activate downstream signal transduction pathways important in development and tissue homeostasis. Wnts can signal through one of several pathways, including the conserved Wnt/?catenin pathway. The Wnt/?-catenin pathway is activated by Wnt ligands binding to Frizzled serpentine receptors and to LRP5/ 6 co-receptors, leading to the post-translational regulation of the stability of catenin. In the absence of a Wnt signal, cytosolic CTNNB1 is bound by the scaffolding proteins Adenomatous Polyposis Coli and AXIN1, and the kinases Casein Kinase 1 and Glycogen Synthase Kinase. Sequential phosphorylation of CTNNB1 by CSNK1A1 and GSK3 leads to its recognition by a ubiquitin ligase protein complex and its subsequent degradation by the proteasome. Upon activation of Wnt/?-catenin signaling, this ����destruction complex���� is inhibited, resulting in accumulation of newly translated CTNNB1, which then translocates to the nucleus where it acts as a co-activator during transcription of target genes that ultimately lead to context-dependent changes in cell proliferation, specification, or differentiation. Wnt/?-catenin-dependent transcription plays critical roles in both embryonic development and in adults. Examination of mice and zebrafish that are transgenic for ?-catenin-dependent reporters has revealed that ?-catenin signaling is spatially and temporally regulated. Not surprisingly, Wnt-catenin signaling plays many roles in development, including patterning of all three germ layers. In addition, we and others have shown that ectopic activation of the Wnt/?-catenin pathway can drive differentiation of
