ArticlePloS one2021
Small molecule allosteric inhibitors of RORγt block Th17-dependent inflammation and associated gene expression in vivo.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 8 citations in OpenAlex.
- Neuronal expression of retinoid-related orphan receptor gamma (RORγ) and revisiting its role in the central nervous system.Scientific reports · 2026Article
- Neuronal expression of Retinoid-Related Orphan Receptor Gamma (RORγ) and revisiting its role in the Central Nervous System.bioRxiv : the preprint server for biology · 2026Article
- Aptamers Targeting IL17A and Its Receptor Suppress IL17 Signaling in Different Cell Types.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Inhibition of the RORC/GPX4 mediated ferroptosis regulatory axis suppresses tumor growth and alleviates enzalutamide resistance in prostate cancer.Cellular & molecular biology letters · 2026Article
- Review
- Beneficial Probiotics with New Cancer Therapies for Improved Treatment of Hepatocellular Carcinoma.Diseases (Basel, Switzerland) · 2025Review
- Exosomal miR-181a-5p derived from SAOS-2 cells promotes macrophages M2 polarization by targeting RORA.The Kaohsiung journal of medical sciences · 2023Article
- IL-17 in osteoarthritis: A narrative review.Open life sciences · 2023Review
- Potential tactics with certain gut microbiota for the treatment of unresectable hepatocellular carcinoma.Exploration of targeted anti-tumor therapy · 2023Article
Corrections and comments
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Authors and funding
24 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retinoic acid receptor-related orphan nuclear receptor (ROR) γt is a member of the RORC nuclear hormone receptor family of transcription factors. RORγt functions as a critical regulator of thymopoiesis and immune responses. RORγt is expressed in multiple immune cell populations including Th17 cells, where its primary function is regulation of immune responses to bacteria and fungi through IL-17A production. However, excessive IL-17A production has been linked to numerous autoimmune diseases. Moreover, Th17 cells have been shown to elicit both pro- and anti-tumor effects. Thus, modulation of the RORγt/IL-17A axis may represent an attractive therapeutic target for the treatment of autoimmune disorders and some cancers. Herein we report the design, synthesis and characterization of three selective allosteric RORγt inhibitors in preclinical models of inflammation and tumor growth. We demonstrate that these compounds can inhibit Th17 differentiation and maintenance in vitro and Th17-dependent inflammation and associated gene expression in vivo, in a dose-dependent manner. Finally, RORγt inhibitors were assessed for efficacy against tumor formation. While, RORγt inhibitors were shown to inhibit tumor formation in pancreatic ductal adenocarcinoma (PDAC) organoids in vitro and modulate RORγt target genes in vivo, this activity was not sufficient to delay tumor volume in a KP/C human tumor mouse model of pancreatic cancer.
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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.