ArticleOncotarget2014
Mode and specificity of binding of the small molecule GANT61 to GLI determines inhibition of GLI-DNA binding.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 126 citations in OpenAlex.
- Defective HNF1A hinders GLI3 processing favoring duodenal versus pancreatic fate, thus leading to intestinal elongation in vivo.Genes & development · 2026Article
- Identification of Raptor and GLI1 as USP37 substrates highlight its context-specific function in medulloblastoma cells.Oncogene · 2026Article
- Solasodine inhibited the proliferation of gastric cancer cells through suppression of Hedgehog/Gli1 signaling.Food science and biotechnology · 2025Article
- Translational drugs targeting cancer stem cells in triple-negative breast cancer.Molecular therapy. Oncology · 2025Review
- Probing the biological efficacy and mechanistic pathways of natural compounds in breast cancer therapy via the Hedgehog signaling pathway.Journal of pharmaceutical analysis · 2025Review
- Identification of Novel GANT61 Analogs with Activity in Hedgehog Functional Assays and GLI1-Dependent Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- Daunorubicin induces GLI1‑dependent apoptosis in colorectal cancer cell lines.International journal of oncology · 2024Article
- Hedgehog signaling via its ligand DHH acts as cell fate determinant during skeletal muscle regeneration.Nature communications · 2023Article
- Developmental exposure to domoic acid targets reticulospinal neurons and leads to aberrant myelination in the spinal cord.Scientific reports · 2023Article
- Multiprotein GLI Transcriptional Complexes as Therapeutic Targets in Cancer.Life (Basel, Switzerland) · 2022Review
- Modulation of Hedgehog Signaling for the Treatment of Basal Cell Carcinoma and the Development of Preclinical Models.Biomedicines · 2022Review
- Quinolines and Oxazino-quinoline Derivatives as Small Molecule GLI1 Inhibitors Identified by Virtual Screening.ACS medicinal chemistry letters · 2022Article
- Oxysterol derivatives Oxy186 and Oxy210 inhibit WNT signaling in non-small cell lung cancer.Cell & bioscience · 2022Article
- Functional Disruption of Gli1-DNA Recognition via a Cobalt(III) Complex.ChemMedChem · 2022Article
- Delivery of Targeted Co(III)-DNA Inhibitors of Gli Proteins to Disrupt Hedgehog Signaling.Bioconjugate chemistry · 2022Article
- Quantitative Longitudinal Imaging Reveals that Inhibiting Hedgehog Activity Alleviates the Hypoxic Tumor Landscape.Molecular cancer research : MCR · 2022Article
- Sonic Hedgehog Signaling in Cerebellar Development and Cancer.Frontiers in cell and developmental biology · 2022Review
- Hedgehog signaling is controlled by Rac1 activity.Theranostics · 2022Article
- Hedgehog/GLI1 Transcriptionally Regulates FANCD2 in Ovarian Tumor Cells: Its Inhibition Induces HR-Deficiency and Synergistic Lethality with PARP Inhibition.Neoplasia (New York, N.Y.) · 2021Article
- SAR insights into TET2 catalytic domain inhibition: Synthesis of 2-Hydroxy-4-Methylene-pentanedicarboxylates.Bioorganic & medicinal chemistry · 2021Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The GLI genes, GLI1 and GLI2, are transcription factors that regulate target genes at the distal end of the canonical Hedgehog (HH) signaling pathway (SHH->PTCH->SMO->GLI), tightly regulated in embryonic development, tissue patterning and differentiation. Both GLI1 and GLI2 are oncogenes, constitutively activated in many types of human cancers. In colon cancer cells oncogenic KRAS-GLI signaling circumvents the HH-SMO-GLI axis to channel through and activate GLI in the transcriptional regulation of target genes. We have observed extensive cell death in a panel of 7 human colon carcinoma cell lines using the small molecule GLI inhibitor GANT61. Using computational docking and experimental confirmation by Surface Plasmon Resonance, GANT61 binds to the 5-zinc finger GLI1 protein between zinc fingers 2 and 3 at sites E119 and E167, independent of the GLI-DNA binding region, and conserved between GLI1 and GLI2. GANT61 does not bind to other zinc finger transcription factors (KLF4, TFIIβ). Mutating the predicted GANT61 binding sites in GLI1 significantly inhibits GANT61-GLI binding and GLI-luciferase activity. Data establish the specificity of GANT61 for targeting GLI, and substantiate the critical role of GLI in cancer cell survival. Thus, targeting GLI in cancer therapeutics may be of high impact.
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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.