ArticleNature chemical biology2014
Target identification for a Hedgehog pathway inhibitor reveals the receptor GPR39.
Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 66 citations in OpenAlex.
- Novel Roles of GPCRs in the Renal Collecting Duct.Physiology (Bethesda, Md.) · 2026Review
- GPR39 activation inhibits AQP2 trafficking and alters cytoskeletal organization.American journal of physiology. Cell physiology · 2026Article
- Evaluation of Benzo[cd]indol-2(1H)-ones as Downstream Hedgehog Pathway Inhibitors.ChemistryOpen · 2025Article
- Covalent functionalization of G protein-coupled receptors by small molecular probes.RSC chemical biology · 2025Review
- Targeted protein degradation reveals BET bromodomains as the cellular target of Hedgehog pathway inhibitor-1.Nature communications · 2023Article
- TC-G 1008 facilitates epileptogenesis by acting selectively at the GPR39 receptor but non-selectively activates CREB in the hippocampus of pentylenetetrazole-kindled mice.Cellular and molecular life sciences : CMLS · 2023Article
- Inhibition of GPR39 restores defects in endothelial cell-mediated neovascularization under the duress of chronic hyperglycemia: Evidence for regulatory roles of the sonic hedgehog signaling axis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Zinc-Sensing Receptor GPR39 in Physiology and as a Pharmacological Target.International journal of molecular sciences · 2021Review
- Orchestration of Intracellular Circuits by G Protein-Coupled Receptor 39 for Hepatitis B Virus Proliferation.International journal of molecular sciences · 2020Article
- microRNA-1914, which is regulated by lncRNA DUXAP10, inhibits cell proliferation by targeting the GPR39-mediated PI3K/AKT/mTOR pathway in HCC.Journal of cellular and molecular medicine · 2019Article
- Extracellular vesicles mediate improved functional outcomes in engineered cartilage produced from MSC/chondrocyte cocultures.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Discovery of new GPCR ligands to illuminate new biology.Nature chemical biology · 2017Article
- Nuclear/cytoplasmic transport defects in BBS6 underlie congenital heart disease through perturbation of a chromatin remodeling protein.PLoS genetics · 2017Article
- Solasonine, A Natural Glycoalkaloid Compound, Inhibits Gli-Mediated Transcriptional Activity.Molecules (Basel, Switzerland) · 2016Article
- An essential role for Grk2 in Hedgehog signalling downstream of Smoothened.EMBO reports · 2016Article
- Advances in targeted and immunobased therapies for colorectal cancer in the genomic era.OncoTargets and therapy · 2016Review
- Ins and outs of GPCR signaling in primary cilia.EMBO reports · 2015Review
- Review
- Pharmacology and physiology of gastrointestinal enteroendocrine cells.Pharmacology research & perspectives · 2015Review
- GPR39 marks specific cells within the sebaceous gland and contributes to skin wound healing.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
30 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hedgehog (Hh) signaling determines cell fate during development and can drive tumorigenesis. We performed a screen for new compounds that can impinge on Hh signaling downstream of Smoothened (Smo). A series of cyclohexyl-methyl aminopyrimidine chemotype compounds ('CMAPs') were identified that could block pathway signaling in a Smo-independent manner. In addition to inhibiting Hh signaling, the compounds generated inositol phosphates through an unknown GPCR. Correlation of GPCR mRNA expression levels with compound activity across cell lines suggested the target to be the orphan receptor GPR39. RNA interference or cDNA overexpression of GPR39 demonstrated that the receptor is necessary for compound activity. We propose a model in which CMAPs activate GPR39, which signals to the Gli transcription factors and blocks signaling. In addition to the discovery of GPR39 as a new target that impinges on Hh signaling, we report on small-molecule modulators of the receptor that will enable in vitro interrogation of GPR39 signaling in different cellular contexts.
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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.