ArticleProceedings of the National Academy of Sciences of the United States of America2012
Small molecule inhibitors of Smoothened ciliary localization and ciliogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 57 citations in OpenAlex.
- Primary cilia promote resistance to EGFR tyrosine kinase inhibitor, osimertinib, in non-small cell lung cancer.bioRxiv : the preprint server for biology · 2026Article
- Ciliary-Mediated Mechanotransduction in Skeletal Development and Diseases.Results and problems in cell differentiation · 2026Review
- Oncogenic B-Raf proto-oncogene, serine/threonine kinase-mediated hedgehog signalling in the pathogenesis and targeted therapy of melanoma.World journal of clinical oncology · 2025Review
- Cilia at the crossroad: convergence of regulatory mechanisms to govern cilia dynamics during cell signaling and the cell cycle.Cell & bioscience · 2025Review
- Proximity based proteomics reveals Git1 as a regulator of Smoothened signaling.bioRxiv : the preprint server for biology · 2025Article
- Deciphering vesicle-assisted transport mechanisms in cytoplasm to cilium trafficking.Frontiers in cellular neuroscience · 2024Review
- Review
- Targeted protein degradation reveals BET bromodomains as the cellular target of Hedgehog pathway inhibitor-1.Nature communications · 2023Article
- A Potent Antagonist of Smoothened in Hedgehog Signaling for Epilepsy.International journal of molecular sciences · 2022Article
- Functional aspects of primary cilium in signaling, assembly and microenvironment in cancer.Journal of cellular physiology · 2021Review
- Identification of a potent antagonist of smoothened in hedgehog signaling.Cell & bioscience · 2021Article
- Cilium Expression Score Predicts Glioma Survival.Frontiers in genetics · 2021Article
- An ABC Transporter Drives Medulloblastoma Pathogenesis by Regulating Sonic Hedgehog Signaling.Cancer research · 2020Article
- NRF2 negatively regulates primary ciliogenesis and hedgehog signaling.PLoS biology · 2020Article
- Sonic hedgehog signaling in epithelial tissue development.Regenerative medicine research · 2019Article
- Review
- TGF-β receptor I/II trafficking and signaling at primary cilia are inhibited by ceramide to attenuate cell migration and tumor metastasis.Science signaling · 2017Article
- Hedgehog Signaling: From Basic Biology to Cancer Therapy.Cell chemical biology · 2017Review
- INPP5E regulates phosphoinositide-dependent cilia transition zone function.The Journal of cell biology · 2017Article
- Novel small molecules targeting ciliary transport of Smoothened and oncogenic Hedgehog pathway activation.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Vertebrate Hedgehog (Hh) signals involved in development and some forms of cancer, such as basal cell carcinoma, are transduced by the primary cilium, a microtubular projection found on many cells. A critical step in vertebrate Hh signal transduction is the regulated movement of Smoothened (Smo), a seven-transmembrane protein, to the primary cilium. To identify small molecules that interfere with either the ciliary localization of Smo or ciliogenesis, we undertook a high-throughput, microscopy-based screen for compounds that alter the ciliary localization of YFP-tagged Smo. This screen identified 10 compounds that inhibit Hh pathway activity. Nine of these Smo antagonists (SA1-9) bind Smo, and one (SA10) does not. We also identified two compounds that inhibit ciliary biogenesis, which block microtubule polymerization or alter centrosome composition. Differential labeling of cell surface and intracellular Smo pools indicates that SA1-7 and 10 specifically inhibit trafficking of intracellular Smo to cilia. In contrast, SA8 and 9 recruit endogenous Smo to the cilium in some cell types. Despite these different mechanisms of action, all of the SAs inhibit activation of the Hh pathway by an oncogenic form of Smo, and abrogate the proliferation of basal cell carcinoma-like cancer cells. The SA compounds may provide alternative means of inhibiting pathogenic Hh signaling, and our study reveals that different pools of Smo move into cilia through distinct mechanisms.
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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.