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SOLUTIONS FORWNT PATHWAY SCREENINGHigh-throughput Assays for Canonical Wnt Pathway AnalysisSince the discovery of the Wnt gene over 30 years ago <strong>as</strong> the Int1 proto-oncogene involved inthe pathology of Mouse Mammary Tumor Virus (MMTV), Wnt expression and signal transductionhave been identified <strong>as</strong> critical components in regulating embryogenesis, cell proliferation,and bone, glucose, and lipid metabolism. Perturbations in Wnt expression, surface receptors,signaling partners (including β-catenin and GSK-3β), and the battery of Wnt-regulated genes(collectively the canonical Wnt pathway) are known to manifest in a variety of clinicallyrelevant dise<strong>as</strong>e states, including cancer, osteoporosis, cardiov<strong>as</strong>cular dise<strong>as</strong>e, diabetes, andneurodegeneration.WNT MODULATOR SCREENINGWntWIF-1PATHWAY ANALYSISScreen-Well ®Wnt PathwayLibrarySOSTDKKLRP5/6KremenLRP5/6WntFrizzledsFRPProte<strong>as</strong>omaldegradationLRP5/6WntFrizzledAxin Frat-1DshELISAsDkk-1, GSK-3β,[pSer9] GSK-3β,β-cateninLeading Light TMWnt ReporterAssayAPCGSK3AxinPβ-CateninGSK3β-CateninNuclearLocalizationp300/CBPβ-Cateninβ-Cateninβ-CateninWnt Regulated Gene ExpressionTCF/LEFAntibodiesGSK-3β,GSK-3 α/β,Dishevelled-1,Dishevelled-2,β-cateninProteinsAPC, Dkk-1,GSK-3β, Wnt-3a,C<strong>as</strong>ein Kin<strong>as</strong>e IIWnt InhibitionReceptor Activationβ-catenin phosphorylation by GSK3ββ-catenin degredationWnt ActivationReceptor Activationβ-catenin phosphorylation by GSK3ββ-catenin nuclear localizationCellular AnalysisWe have extensive experience in buildingnext generation cell b<strong>as</strong>ed <strong>as</strong>says for use indrug development, secondary screening, andpathway analysis. Our Leading Light andCELLestial ® <strong>as</strong>say systems are optimizedto meet the needs of demanding highthroughputapplications to deliver better,high-quality hits.Our portfolio of over 300 ELISA kits includessensitive, specific <strong>as</strong>says for key signalingproteins in the canonical Wnt pathway in avariety of species. In addition, our catalogof over 3000 antibodies and recombinantproteins includes thoroughly validatedreagents for dissection of Wnt pathwaysignaling.Small Molecule ChemistryOur long-standing, flagship Screen-Well ®Compound Library portfolio offers ane<strong>as</strong>y, ready-to-use method to streamlinecompound screening. Included within ourthousands of stand-alone small molecules isa unique collection of Wnt Pathway targetingcompounds <strong>as</strong> well <strong>as</strong> focused libraries forkin<strong>as</strong>e inhibitors, natural products, prote<strong>as</strong>einhibitors, nuclear receptors, autophagyregulators, and more.Through our supplier network built over a 25year history, we have the ability to rapidlyand inexpensively source traditional, custom,and bulk compounds in the gram to kilogramscale. We complete our sourcing usingstringent quality control standards withstate-of-the-art methods.
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