ArticleThe Journal of biological chemistry2015
Structure-based Discovery of Novel Small Molecule Wnt Signaling Inhibitors by Targeting the Cysteine-rich Domain of Frizzled.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Refolding Protocol of the Cysteine-Rich Domain of Frizzled8 from Inclusion Bodies.International journal of molecular sciences · 2026Article
- Targeting frizzled receptors (FZDs) for anti-tumor therapy: From orthosteric to allosteric inhibition.Acta pharmaceutica Sinica. B · 2026Review
- WNT signaling in cancer: molecular mechanisms and potential therapies.Molecular biomedicine · 2025Review
- Isolation and characterization of a bioactive compound from Sphingomonas sanguinis DM with cytotoxic and molecular docking analysis.Scientific reports · 2025Article
- Evaluation of the Anti-Inflammatory Effects of Novel Fatty Acid-Binding Protein 4 Inhibitors in Microglia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Frizzled receptors: gatekeepers of Wnt signaling in development and disease.Frontiers in cell and developmental biology · 2025Review
- Challenging Reported Frizzled-Targeting Compounds in Selective Assays Reveals Lack of Functional Inhibition and Claimed Profiles.ACS pharmacology & translational science · 2024Article
- A New Wave of Targeting 'Undruggable' Wnt Signaling for Cancer Therapy: Challenges and Opportunities.Cells · 2023Review
- Small-molecule Wnt inhibitors are a potential novel therapy for intestinal fibrosis in Crohns disease.Clinical science (London, England : 1979) · 2022Article
- Characterizing the extracellular matrix transcriptome of cervical, endometrial, and uterine cancers.Matrix biology plus · 2022Article
- R-etodolac is a more potent Wnt signaling inhibitor than enantiomer, S-etodolac.Biochemistry and biophysics reports · 2022Article
- Wnt signaling activation: targets and therapeutic opportunities for stem cell therapy and regenerative medicine.RSC chemical biology · 2021Review
- Carboxylesterase Notum Is a Druggable Target to Modulate Wnt Signaling.Journal of medicinal chemistry · 2021Article
- Pharmacologically Targeting the WNT/β-Catenin Signaling Cascade: Avoiding the Sword of Damocles.Handbook of experimental pharmacology · 2021Article
- Wnt signaling in breast cancer: biological mechanisms, challenges and opportunities.Molecular cancer · 2020Review
- Article
- Antiepileptic Drug Carbamazepine Binds to a Novel Pocket on the Wnt Receptor Frizzled-8.Journal of medicinal chemistry · 2020Article
- New Advances in Canonical Wnt/β-Catenin Signaling in Cancer.Cancer management and research · 2020Review
- Identification of Genes Regulating Breast Cancer Dormancy in 3D Bone Endosteal Niche Cultures.Molecular cancer research : MCR · 2019Article
- More Favorable Palmitic Acid Over Palmitoleic Acid Modification of Wnt3 Ensures Its Localization and Activity in Plasma Membrane Domains.Frontiers in cell and developmental biology · 2019Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Frizzled is the earliest discovered glycosylated Wnt protein receptor and is critical for the initiation of Wnt signaling. Antagonizing Frizzled is effective in inhibiting the growth of multiple tumor types. The extracellular N terminus of Frizzled contains a conserved cysteine-rich domain that directly interacts with Wnt ligands. Structure-based virtual screening and cell-based assays were used to identify five small molecules that can inhibit canonical Wnt signaling and have low IC50 values in the micromolar range. NMR experiments confirmed that these compounds specifically bind to the Wnt binding site on the Frizzled8 cysteine-rich domain with submicromolar dissociation constants. Our study confirms the feasibility of targeting the Frizzled cysteine-rich domain as an effective way of regulating canonical Wnt signaling. These small molecules can be further optimized into more potent therapeutic agents for regulating abnormal Wnt signaling by targeting Frizzled.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.