ArticleJournal of translational medicine2022
Discovery of a pyrano[2,3-b]pyridine derivative YX-2102 as a cannabinoid receptor 2 agonist for alleviating lung fibrosis.
Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- CB2R agonism protects intestinal epithelium through β-catenin/HoxA10 loop in radiation injury.Journal of translational medicine · 2026Article
- Protective effect of cannabinoid type II receptor ligand on bleomycin-induced pulmonary fibrosis in mice.PloS one · 2026Article
- Cannabidiol inhibits TGF-β1-induced epithelial-mesenchymal transition in human conjunctival epithelial cells by interrupting TGF-β/Smad signaling.Scientific reports · 2025Article
- Natural products for anti-fibrotic therapy in idiopathic pulmonary fibrosis: marine and terrestrial insights.Frontiers in pharmacology · 2025Review
- Therapeutic potential of agents targeting cannabinoid type 2 receptors in organ fibrosis.Pharmacology research & perspectives · 2024Review
- Article
- Cannabinoid receptor ligands modulate fibrosis and inflammation in idiopathic pulmonary fibrosis: a preliminary study.Turkish journal of biology = Turk biyoloji dergisi · 2024Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundPharmacological modulation of cannabinoid 2 receptor (CB2R) is a promising therapeutic strategy for pulmonary fibrosis (PF). Thus, to develop CB2R selective ligands with new chemical space has attracted much research interests. This work aims to discover a novel CB2R agonist from an in-house library, and to evaluate its therapeutic effects on PF model, as well as to disclose the pharmacological mechanism.
methodsVirtual screening was used to identify the candidate ligand for CB2R from a newly established in-house library. Both in vivo experiments on PF rat model and in vitro experiments on cells were performed to investigate the therapeutic effects of the lead compound and underlying mechanism.
resultsA "natural product-like" pyrano[2,3-b]pyridine derivative, YX-2102 was identified that bound to CB2R with high affinity. Intraperitoneal YX-2102 injections significantly ameliorated lung injury, inflammation and fibrosis in a rat model of PF induced by bleomycin (BLM). On one hand, YX-2102 inhibited inflammatory response at least partially through modulating macrophages polarization thereby exerting protective effects. Whereas, on the other hand, YX-2102 significantly upregulated CB2R expression in alveolar epithelial cells in vivo. Its pretreatment inhibited lung alveolar epithelial-to-mesenchymal transition (EMT) in vitro and PF model induced by transforming growth factor beta-1 (TGF-β1) via a CB2 receptor-dependent pathway. Further studies suggested that the Nrf2-Smad7 pathway might be involved in.
conclusionThese findings suggest that CB2R is a potential target for PF treatment and YX-2102 is a promising CB2R agonist with new chemical space.
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Registered trials
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