ArticleBioorganic & medicinal chemistry2018
Identification of DK419, a potent inhibitor of Wnt/β-catenin signaling and colorectal cancer growth.
Article in Bioorganic & medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- A novel drug prejudice scaffold-imidazopyridine-conjugate can promote cell death in a colorectal cancer model by binding to β-catenin and suppressing the Wnt signaling pathway.Journal of advanced research · 2025Article
- Blocking the WNT/β-catenin pathway in cancer treatment:pharmacological targets and drug therapeutic potential.Heliyon · 2024Review
- A New Wave of Targeting 'Undruggable' Wnt Signaling for Cancer Therapy: Challenges and Opportunities.Cells · 2023Review
- Blocking the Wnt/β‑catenin signaling pathway to treat colorectal cancer: Strategies to improve current therapies (Review).International journal of oncology · 2023Review
- Wnt signaling in colorectal cancer: pathogenic role and therapeutic target.Molecular cancer · 2022Review
- Signaling pathways and their potential therapeutic utility in esophageal squamous cell carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Wnt signaling in breast cancer: biological mechanisms, challenges and opportunities.Molecular cancer · 2020Review
- HMGA2 regulates acute myeloid leukemia progression and sensitivity to daunorubicin via Wnt/β-catenin signaling.International journal of molecular medicine · 2019Article
- Niclosamide-induced Wnt signaling inhibition in colorectal cancer is mediated by autophagy.The Biochemical journal · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
The Wnt signaling pathway is critical for normal tissue development and is an underlying mechanism of disease when dysregulated. Previously, we reported that the drug Niclosamide inhibits Wnt/β-catenin signaling by decreasing the cytosolic levels of Dishevelled and β-catenin, and inhibits the growth of colon cancers both in vitro and in vivo. Since the discovery of Niclosamide's anthelmintic activity, a growing body of literature indicates that Niclosamide is a multifunctional drug. In an effort to identify derivatives of Niclosamide with improved pharmacokinetic properties that maintain the multifunctional drug activity of Niclosamide for clinical evaluation, we designed DK419, a derivative containing a 1H-benzo[d]imidazole-4-carboxamide substructure, using the structure-activity relationships (SAR) of the Niclosamide salicylanilide chemotype. Similar to Niclosamide, we found DK419 inhibited Wnt/β-catenin signaling, altered cellular oxygen consumption rate and induced production of pAMPK. Moreover, we found DK419 inhibited the growth of CRC tumor cells in vitro, had good plasma exposure when dosed orally, and inhibited the growth of patient derived CRC240 tumor explants in mice dosed orally. DK419, a derivative of Niclosamide with multifunctional activity and improved pharmacokinetic properties, is a promising agent to treat colorectal cancer, Wnt-related diseases and other diseases in which Niclosamide has demonstrated functional activity.
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Registered trials
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.