ArticleACS medicinal chemistry letters2021
Covalent Occlusion of the RORγt Ligand Binding Pocket Allows Unambiguous Targeting of an Allosteric Site.
Article in ACS medicinal chemistry letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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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
4 citing papers in PubMed, 11 citations in OpenAlex.
- Structural Elucidation and Covalent Modulation of the Autorepressed Orphan Nuclear Receptor NR2F6.ACS chemical biology · 2025Article
- Targeting the Alternative Vitamin E Metabolite Binding Site Enables Noncanonical PPARγ Modulation.Journal of the American Chemical Society · 2023Article
- The application of machine learning methods to the prediction of novel ligands for RORComputational and structural biotechnology journal · 2023Article
- Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs.Journal of molecular biology · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nuclear receptor RORγt is a key positive regulator in the differentiation and proliferation of T helper 17 (Th17) cells and the production of proinflammatory cytokines like IL-17a. Dysregulation of this pathway can result in the development of various autoimmune diseases, and inhibition of RORγt with small molecules thus holds great potential as a therapeutic strategy. RORγt has a unique allosteric ligand binding site in the ligand binding domain, which is distinct from the canonical, orthosteric binding site. Allosteric modulation of RORγt shows high potential, but the targeted discovery of novel allosteric ligands is highly challenging via currently available methods. Here, we introduce covalent, orthosteric chemical probes for RORγt that occlude the binding of canonical, orthosteric ligands but still allow allosteric ligand binding. Ultimately, these probes could be used to underpin screening approaches for the unambiguous and rapid identification of novel allosteric RORγt ligands.
Identifiers
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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.