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Discovery of a Novel Class of Bioactive Molecules Suppressing Pathogenic Fibroblast Activation through Hyou1 Targeting

GSE237395 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2024/03/12 Platform GPL18635
Summary
Fibroblasts play an important role in fibrosis, chronic inflammatory diseases (CIDs) and cancer. Targeting their pathogenicity is crucial, considering the limitations and side effects of existing biologic therapies that focus on inflammatory mediators (TNFα/IL-6). Herein, a multidisciplinary approach utilizing activated primary fibroblasts (PFs) and macrophages (MFs), which are key regulators in inflammation and fibrosis, is presented. The research encompasses medicinal chemistry, molecular phenotyping, mechanism of action studies, RNA-sequencing analysis and ADMET/PK/in vivo evaluation. A novel anti-inflammatory pharmacophore acting through Hypoxia up-regulated protein 1 (Hyou1) was discovered, thus emerging the potential of Hyou1 down-regulation/inhibition in fibroblast-related disorders. The study highlights the need for further investigation into the effects of Hyou1 activity on fibroblasts while providing the first reported Hyou1 small molecule inhibitor leads for drug discovery.
Published in
Discovery of the First-in-Class Inhibitors of Hypoxia Up-Regulated Protein 1 (HYOU1) Suppressing Pathogenic Fibroblast Activation
Papadopoulou D, Mavrikaki V, Charalampous F et al. · Angewandte Chemie (International ed. in English) 2024 · PMID 38339863 · doi:10.1002/anie.202319157
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Also filed as BioProject PRJNA994878 and SRA study SRP449559. Searching any of these in the dataset finder brings you back here.

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