ArticleCancer research2014
Pyrvinium attenuates Hedgehog signaling downstream of smoothened.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 74 citations in OpenAlex.
- Transforming Outcomes in Advanced Basal Cell Carcinoma: The Evolving Role of Systemic Therapy.American journal of clinical dermatology · 2026Review
- CK1α agonists attenuate medulloblastoma stemness and relapse risk.Cell death & disease · 2026Article
- A High-Throughput Drug Repurposing Strategy to Treat TBX2 and/or TBX3 Dependent Cancers.Cancer medicine · 2024Article
- Mechanistic insights into medulloblastoma relapse.Pharmacology & therapeutics · 2024Review
- Identification of Novel GANT61 Analogs with Activity in Hedgehog Functional Assays and GLI1-Dependent Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- Recurrent UBE3C-LRP5 translocations in head and neck cancer with therapeutic implications.NPJ precision oncology · 2024Article
- Targeting Stem Cells and Dysplastic Features With Dual MEK/ERK and STAT3 Suppression in Gastric Carcinogenesis.Gastroenterology · 2024Article
- Current Status of Hedgehog Signaling Inhibitors.Current topics in medicinal chemistry · 2024Review
- The FDA-Approved Drug Pyrvinium Selectively Targets ERCancers · 2022Article
- Pyrvinium Pamoate: Past, Present, and Future as an Anti-Cancer Drug.Biomedicines · 2022Review
- Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Hedgehog signaling mechanism and role in cancer.Seminars in cancer biology · 2022Review
- Molecular Mechanisms Involving the Sonic Hedgehog Pathway in Lung Cancer Therapy: Recent Advances.Frontiers in oncology · 2022Review
- Article
- Hedgehog Signaling in Myeloid Malignancies.Cancers · 2021Review
- Switching Hedgehog inhibitors and other strategies to address resistance when treating advanced basal cell carcinoma.Oncotarget · 2021Review
- Medulloblastoma drugs in development: Current leads, trials and drawbacks.European journal of medicinal chemistry · 2021Review
- Exploration of databases and methods supporting drug repurposing: a comprehensive survey.Briefings in bioinformatics · 2021Review
- Drug Repurposing in Medulloblastoma: Challenges and Recommendations.Current treatment options in oncology · 2020Review
- Pyrvinium Pamoate Induces Death of Triple-Negative Breast Cancer Stem-Like Cells and Reduces Metastases through Effects on Lipid Anabolism.Cancer research · 2020Article
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
The Hedgehog (HH) signaling pathway represents an important class of emerging developmental signaling pathways that play critical roles in the genesis of a large number of human cancers. The pharmaceutical industry is currently focused on developing small molecules targeting Smoothened (Smo), a key signaling effector of the HH pathway that regulates the levels and activity of the Gli family of transcription factors. Although one of these compounds, vismodegib, is now FDA-approved for patients with advanced basal cell carcinoma, acquired mutations in Smo can result in rapid relapse. Furthermore, many cancers also exhibit a Smo-independent activation of Gli proteins, an observation that may underlie the limited efficacy of Smo inhibitors in clinical trials against other types of cancer. Thus, there remains a critical need for HH inhibitors with different mechanisms of action, particularly those that act downstream of Smo. Recently, we identified the FDA-approved anti-pinworm compound pyrvinium as a novel, potent (IC50, 10 nmol/L) casein kinase-1α (CK1α) agonist. We show here that pyrvinium is a potent inhibitor of HH signaling, which acts by reducing the stability of the Gli family of transcription factors. Consistent with CK1α agonists acting on these most distal components of the HH signaling pathway, pyrvinium is able to inhibit the activity of a clinically relevant, vismodegib -resistant Smo mutant, as well as the Gli activity resulting from loss of the negative regulator suppressor of fused. We go on to demonstrate the utility of this small molecule in vivo, against the HH-dependent cancer medulloblastoma, attenuating its growth and reducing the expression of HH biomarkers.
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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.