ArticleJournal of medicinal chemistry2012
Wnt inhibition correlates with human embryonic stem cell cardiomyogenesis: a structure-activity relationship study based on inhibitors for the Wnt response.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 66 citations in OpenAlex.
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- Recent advances on small molecules in osteogenic differentiation of stem cells and the underlying signaling pathways.Stem cell research & therapy · 2022Review
- Small-molecule probe reveals a kinase cascade that links stress signaling to TCF/LEF and Wnt responsiveness.Cell chemical biology · 2021Article
- Proteome-wide Analysis Reveals Substrates of E3 Ligase RNF146 Targeted for Degradation.Molecular & cellular proteomics : MCP · 2020Article
- Role of Curcuminoids and Tricalcium Phosphate Ceramic in Rat Spinal Fusion.Tissue engineering. Part C, Methods · 2020Article
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- New Strategies to Enhance Myocardial Regeneration: Expectations and Challenges from Preclinical Evidence.Current stem cell research & therapy · 2020Review
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- Low Resting Membrane Potential and Low Inward Rectifier Potassium Currents Are Not Inherent Features of hiPSC-Derived Cardiomyocytes.Stem cell reports · 2018Article
- Differentiation of cardiomyocytes and generation of human engineered heart tissue.Nature protocols · 2017Article
- Automated Contraction Analysis of Human Engineered Heart Tissue for Cardiac Drug Safety Screening.Journal of visualized experiments : JoVE · 2017Article
- Possible Muscle Repair in the Human Cardiovascular System.Stem cell reviews and reports · 2017Review
- Ca(2+)-Currents in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Effects of Two Different Culture Conditions.Frontiers in pharmacology · 2016Article
- 1,5-Disubstituted benzimidazoles that direct cardiomyocyte differentiation from mouse embryonic stem cells.Bioorganic & medicinal chemistry · 2015Article
- Cholesterol-derived glucocorticoids control early fate specification in embryonic stem cells.Stem cell research · 2015Article
- Small-molecule inhibitors of Wnt signaling pathway: towards novel anticancer therapeutics.Future medicinal chemistry · 2015Review
- TNF receptor-associated factor 6 (TRAF6) mediates the angiotensin-induced non-canonical TGF-β pathway activation of c-kit(+) cardiac stem cells.American journal of translational research · 2015Article
- High content screening for modulators of cardiac differentiation in human pluripotent stem cells.Methods in molecular biology (Clifton, N.J.) · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Human embryonic stem cell-based high-content screening of 550 known signal transduction modulators showed that one "lead" (1, a recently described inhibitor of the proteolytic degradation of Axin) stimulated cardiomyogenesis. Because Axin controls canonical Wnt signaling, we conducted an investigation to determine whether the cardiogenic activity of 1 is Wnt-dependent, and we developed a structure-activity relationship to optimize the cardiogenic properties of 1. We prepared analogues with a range of potencies (low nanomolar to inactive) for Wnt/β-catenin inhibition and for cardiogenic induction. Both functional activities correlated positively (r(2) = 0.72). The optimal compounds induced cardiogenesis 1.5-fold greater than 1 at 30-fold lower concentrations. In contrast, no correlation was observed for cardiogenesis and modulation of transforming growth factor β (TGFβ)/Smad signaling that prominently influences cardiogenesis. Taken together, these data show that Wnt signaling inhibition is essential for cardiogenic activity and that the pathway can be targeted for the design of druglike cardiogenic molecules.
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