ArticlePharmacology research & perspectives2016
Pharmacological evaluation of a series of smoothened antagonists in signaling pathways and after topical application in a depilated mouse model.
Article in Pharmacology research & perspectives, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Article
- Pharmacology ofPharmaceuticals (Basel, Switzerland) · 2024Article
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Topical Delivery of Hedgehog Inhibitors: Current Status and Perspectives.International journal of molecular sciences · 2022Review
- Novel Approaches in Non-Melanoma Skin Cancers-A Focus on Hedgehog Pathway in Basal Cell Carcinoma (BCC).Cells · 2022Review
- Review
- Article
- Inhibition of Hedgehog Signaling Alters Fibroblast Composition in Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- The use of hedgehog antagonists in cancer therapy: a comparison of clinical outcomes and gene expression analyses.Cancer biology & therapy · 2020Article
- Astrocytic Sonic Hedgehog Alleviates Intracerebral Hemorrhagic Brain InjuryFrontiers in cellular neuroscience · 2020Article
- Hedgehog Pathway Inhibition for the Treatment of Basal Cell Carcinoma.Targeted oncology · 2019Review
- Article
- Safety and Tolerability of Sonic Hedgehog Pathway Inhibitors in Cancer.Drug safety · 2019Review
- Reproducibility of academic preclinical translational research: lessons from the development of Hedgehog pathway inhibitors to treat cancer.Open biology · 2018Review
- The role of the Hedgehog signaling pathway in cancer: A comprehensive review.Bosnian journal of basic medical sciences · 2018Review
- Advances in targeted therapy for acute myeloid leukaemia.British journal of haematology · 2018Review
- Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond.Molecular carcinogenesis · 2017Review
- Synthesis and Investigation ofACS medicinal chemistry letters · 2017Article
- Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas.OncoTargets and therapy · 2017Review
- Pharmacological evaluation of a series of smoothened antagonists in signaling pathways and after topical application in a depilated mouse model.Pharmacology research & perspectives · 2016Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Hedgehog (HH) pathway has been linked to the formation of basal cell carcinoma (BCC), medulloblastoma, and other cancers. The recently approved orally active drugs vismodegib (GDC-0449) and sonidegib (LDE-225) were not only efficacious for the treatment of advanced or metastatic BCC by antagonizing the smoothened (SMO) receptor, but also produced important side effects, limiting their use for less invasive BCC. Herein, we compared a large series of SMO antagonists, including GDC-0449 and LDE-225, the clinically tested BMS-833923, CUR-61414, cyclopamine, IPI-926 (saridegib), itraconazole, LEQ-506, LY-2940680 (taladegib), PF-04449913 (glasdegib), and TAK-441 as well as preclinical candidates (PF-5274857, MRT-83) in two SMO-dependent cellular assays and for G-protein activation. We report marked differences in inhibitor potencies between compounds as well as a notable disparity between the G-protein assay and the cellular tests, suggesting that classification of drugs is assay dependent. Furthermore, we explored topical efficacies of SMO antagonists on depilated mice using Gli1 and Ptch1 mRNA quantification in skin as biomarkers of the HH signaling inhibition. This topical model rapidly discriminated drugs in terms of efficacies and potencies for inhibition of both biomarkers. SMO antagonists showed also a large variation in their blood and skin partition, suggesting that some drugs are more favorable for topical application. Overall, our data suggested that in vitro and in vivo efficacious drugs such as LEQ-506 and TAK-441 may be of interest for topical treatment of less invasive BCC with minimal side effects.
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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.