ArticleJournal of medicinal chemistry2025
Insights into the Activation Mechanism of HCA1, HCA2, and HCA3.
Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 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
6 citing papers in PubMed.
- State-Dependent 3D Enhancer Architecture Resolves a Shared Schizophrenia and Multiple Sclerosis Ketone and Lactate Sensing Logic Gate.bioRxiv : the preprint server for biology · 2026Article
- State-Dependent Transcriptomic Collapse of the Brain's Lactate and Ketone Thermodynamic Sensors in Schizophrenia.bioRxiv : the preprint server for biology · 2026Article
- Evolutionary History and Functional Divergence of Hydroxycarboxylic Acid Receptors in Primates.Genome biology and evolution · 2026Article
- A Machine Learning-Guided Approach for Identifying Potential HCAR1 Antagonists in Lactate-Driven Cancers.ACS omega · 2026Article
- The Concise Guide to PHARMACOLOGY 2025/26: G protein-coupled receptors.British journal of pharmacology · 2025Review
- Structure Modeling and Virtual Screening with HCAR3 to Discover Potential Therapeutic Molecules.Pharmaceuticals (Basel, Switzerland) · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hydroxy-carboxylic acid receptors HCA1, HCA2, and HCA3 can be activated by important intermediates of energy metabolism. Despite the research focusing on HCA2, its clinical application has been limited by adverse effects. Therefore, the role of HCA1 as a promising target for the treatment of lipolysis warrants further exploration. As HCAs exhibit high similarity when activated with diverse selective agonists, a conserved yet unique activation mechanism for HCAs remains undisclosed. Herein, we unveil the cryo-electron microscopy structures of the 3,5-DHBA-HCA1-Gi signaling complex, the acifran- and MK6892-bound HCA2-Gi signaling complexes, and the acifran-HCA3-Gi signaling complex. Comparative analysis across HCAs reveals key residues in HCA1 contributing to the stabilization of the ligand-binding pocket. Furthermore, chimeric complexes and mutational analyses identify residues that are pivotal for HCA2 and HCA3 selectivity. Our findings elucidate critical structural insights into the mechanisms of ligand recognition and activation within HCA1 and broaden our comprehension of ligand specificity binding across the HCA family.
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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.