ArticleJournal of the American Chemical Society2013
Discovery of small-molecule modulators of the Sonic Hedgehog pathway.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- 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
- Computational investigation of naturally occurring anticancer agents in regulating Hedgehog pathway proteins.PloS one · 2024Article
- Diversity-oriented synthesis encoded by deoxyoligonucleotides.Nature communications · 2023Article
- Targeted protein degradation reveals BET bromodomains as the cellular target of Hedgehog pathway inhibitor-1.Nature communications · 2023Article
- Medulloblastoma drugs in development: Current leads, trials and drawbacks.European journal of medicinal chemistry · 2021Review
- Design of Hedgehog pathway inhibitors for cancer treatment.Medicinal research reviews · 2019Review
- L-4, a Well-Tolerated and Orally Active Inhibitor of Hedgehog Pathway, Exhibited Potent Anti-tumor Effects Against MedulloblastomaFrontiers in pharmacology · 2019Article
- Synthesis of Benzannulated Medium-ring Lactams via a Tandem Oxidative Dearomatization-Ring Expansion Reaction.Chemistry (Weinheim an der Bergstrasse, Germany) · 2018Article
- Chemical probes and drug leads from advances in synthetic planning and methodology.Nature reviews. Drug discovery · 2018Review
- Review
- A cell based, high throughput assay for quantitative analysis of Hedgehog pathway activation using a Smoothened activation sensor.Scientific reports · 2017Article
- Access to a Structurally Complex Compound Collection via Ring Distortion of the Alkaloid Sinomenine.Organic letters · 2016Article
- Synthesis of oxazocenones via gold(I)-catalyzed 8-endo-dig hydroalkoxylation of alkynamides.Organic letters · 2015Article
- Synthetic Small Molecule Inhibitors of Hh Signaling As Anti-Cancer Chemotherapeutics.Current medicinal chemistry · 2015Review
- Modulators of hepatic lipoprotein metabolism identified in a search for small-molecule inducers of tribbles pseudokinase 1 expression.PloS one · 2015Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The Hedgehog signaling pathway is involved in the development of multicellular organisms and, when deregulated, can contribute to certain cancers, among other diseases. The molecular characterization of the pathway, which has been enabled by small-molecule probes targeting its components, remains incomplete. Here, we report the discovery of two potent, small-molecule inhibitors of the Sonic Hedgehog (Shh) pathway, BRD50837 and BRD9526. Both compounds exhibit stereochemistry-based structure-activity relationships, a feature suggestive of a specific and selective interaction of the compounds with as-yet-unknown cellular target(s) and made possible by the strategy used to synthesize them as members of a stereochemically and skeletally diverse screening collection. The mechanism-of-action of these compounds in some ways shares similarities to that of cyclopamine, a commonly used pathway inhibitor. Yet, in other ways their mechanism-of-action is strikingly distinct. We hope that these novel compounds will be useful probes of this complex signaling pathway.
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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.