ArticleChemistry & biology2014
A cell-permeable inhibitor to trap Gαq proteins in the empty pocket conformation.
Article in Chemistry & biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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.
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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
30 citing papers in PubMed, 54 citations in OpenAlex.
- Innovative Approach Reveals How Receptors Control G Protein State Equilibria.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Does the ERBB/EGF Signaling Network Serve as a Nexus for Oncogenic Signals in Uveal Melanoma?Biomolecules · 2026Review
- ADAM17, induced by Augmenter of Liver Regeneration via G protein-coupled receptor activation, transactivates epidermal growth factor-receptor and reduces classical IL-6 signaling.Cell communication and signaling : CCS · 2026Article
- The thiazolidinedione drug troglitazone inhibits Gq signaling through direct binding to the Gq alpha subunit through inhibition of GDP release.Molecular pharmacology · 2025Article
- Cyclic peptide inhibitors function as molecular glues to stabilize Gq/11 heterotrimers.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- RGS2 is an innate immune checkpoint for suppressing Gαq-mediated IFNγ generation and lung injury.iScience · 2025Article
- Going Rogue: Mechanisms, Regulation, and Roles of Mutationally Activated GMolecular pharmacology · 2024Review
- TMEM16A activation for the fast block to polyspermy in the African clawed frog does not require conventional activation of egg PLCs.The Journal of general physiology · 2023Article
- Coincident Regulation of PLCMolecular pharmacology · 2022Article
- Discovery of small molecule GActa pharmaceutica Sinica. B · 2022Article
- 5-HT2A receptor dysregulation in a schizophrenia relevant mouse model of NMDA receptor hypofunction.Translational psychiatry · 2022Article
- Identification of the nucleotide-free state as a therapeutic vulnerability for inhibition of selected oncogenic RAS mutants.Cell reports · 2022Article
- Strategies towards Targeting Gαi/s Proteins: Scanning of Protein-Protein Interaction Sites To Overcome Inaccessibility.ChemMedChem · 2021Review
- Delineation of molecular determinants for FR900359 inhibition of GThe Journal of biological chemistry · 2020Article
- Tetrahydroimidazo[1,2-a]pyrazine Derivatives: Synthesis and Evaluation as GαChemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- Heterotrimeric GThe Journal of biological chemistry · 2020Review
- Cell-permeable high-affinity tracers for GBritish journal of pharmacology · 2020Article
- Therapeutic targeting of RAS: New hope for drugging the "undruggable".Biochimica et biophysica acta. Molecular cell research · 2020Review
- Biology, pathology, and therapeutic targeting of RAS.Advances in cancer research · 2020Review
- Exploiting RAS Nucleotide Cycling as a Strategy for Drugging RAS-Driven Cancers.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
28 authors at 5 institutions in 3 countries.
Funding
Abstract
In spite of the crucial role of heterotrimeric G proteins as molecular switches transmitting signals from G protein-coupled receptors, their selective manipulation with small molecule, cell-permeable inhibitors still remains an unmet challenge. Here, we report that the small molecule BIM-46187, previously classified as pan-G protein inhibitor, preferentially silences Gαq signaling in a cellular context-dependent manner. Investigations into its mode of action reveal that BIM traps Gαq in the empty pocket conformation by permitting GDP exit but interdicting GTP entry, a molecular mechanism not yet assigned to any other small molecule Gα inhibitor to date. Our data show that Gα proteins may be "frozen" pharmacologically in an intermediate conformation along their activation pathway and propose a pharmacological strategy to specifically silence Gα subclasses with cell-permeable inhibitors.
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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.