ArticleNature communications2015
Identification of an allosteric binding site for RORγt inhibition.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 101 citations in OpenAlex.
- Large-scale comparative virtual screening identifies novel molecular targets underlying the multi-target activity of quercetin in psoriasis.Inflammopharmacology · 2026Article
- SAFR: Enabling Fragment-Based Drug Discovery with a Synthetic Binding Pose Data Set.Journal of chemical information and modeling · 2026Article
- A High-Quality Photoswitchable Probe that Selectively and Potently Regulates the Transcription Factor RORγ.Angewandte Chemie (International ed. in English) · 2024Article
- Investigating the potential role of T helper 17 cells among women experiencing overweight and obesity and their possible therapeutic targeting of the RORγt molecule.Scientific reports · 2024Article
- Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Discovery, Synthesis, and In Vitro Characterization of 2,3 Derivatives of 4,5,6,7-Tetrahydro-Benzothiophene as Potent Modulators of Retinoic Acid Receptor-Related Orphan Receptor γt.Journal of medicinal chemistry · 2023Article
- Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases.Journal of pharmaceutical analysis · 2023Review
- Virtual Screening Strategy to Identify Retinoic Acid-Related Orphan Receptor γt Modulators.Molecules (Basel, Switzerland) · 2023Article
- Macrocyclic Retinoic Acid Receptor-Related Orphan Receptor C2 Inverse Agonists.ACS medicinal chemistry letters · 2023Article
- The application of machine learning methods to the prediction of novel ligands for RORComputational and structural biotechnology journal · 2023Article
- Targeting protein conformations with small molecules to control protein complexes.Trends in biochemical sciences · 2022Review
- Exploring Ligand Binding Domain Dynamics in the NRs Superfamily.International journal of molecular sciences · 2022Article
- Alcohol-driven metabolic reprogramming promotes development of RORγt-deficient thymic lymphoma.Oncogene · 2022Article
- Cooperativity as quantification and optimization paradigm for nuclear receptor modulators.Chemical science · 2022Article
- Statistical Analysis of Protein-Ligand Interaction Patterns in Nuclear Receptor RORγ.Frontiers in molecular biosciences · 2022Article
- Recent applications of computational methods to allosteric drug discovery.Frontiers in molecular biosciences · 2022Review
- Structure-Activity Relationship Studies of Trisubstituted Isoxazoles as Selective Allosteric Ligands for the Retinoic-Acid-Receptor-Related Orphan Receptor γt.Journal of medicinal chemistry · 2021Article
- Covalent Occlusion of the RORγt Ligand Binding Pocket Allows Unambiguous Targeting of an Allosteric Site.ACS medicinal chemistry letters · 2021Article
- Orthosteric and Allosteric Dual Targeting of the Nuclear Receptor RORγt with a Bitopic Ligand.ACS chemical biology · 2021Article
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RORγt is critical for the differentiation and proliferation of Th17 cells associated with several chronic autoimmune diseases. We report the discovery of a novel allosteric binding site on the nuclear receptor RORγt. Co-crystallization of the ligand binding domain (LBD) of RORγt with a series of small-molecule antagonists demonstrates occupancy of a previously unreported allosteric binding pocket. Binding at this non-canonical site induces an unprecedented conformational reorientation of helix 12 in the RORγt LBD, which blocks cofactor binding. The functional consequence of this allosteric ligand-mediated conformation is inhibition of function as evidenced by both biochemical and cellular studies. RORγt function is thus antagonized in a manner molecularly distinct from that of previously described orthosteric RORγt ligands. This brings forward an approach to target RORγt for the treatment of Th17-mediated autoimmune diseases. The elucidation of an unprecedented modality of pharmacological antagonism establishes a mechanism for modulation of nuclear receptors.
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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.