De novo discovery of cyclic peptide inhibitors of IL-11 signaling.

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Tác giả: Bertram Bleck, Claudia Dall'Armi, Anna Demartis, Valentina A Di Biasio, Tony S Gibson, Petro Halkowycz, Antoine Henninot, Ruhi Kamran, Sam Lear, Jing Li, Joanne Miura, Rosalba Tafi

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: England : Bioorganic & medicinal chemistry , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 720732

Interleukin-11 (IL-11), a member of the IL-6 cytokine family, has potential pro-inflammatory and pro-fibrotic roles in pulmonary, hepatic, cardiovascular, renal and intestinal disease pathogenesis, including oncogenesis. The potential for therapeutic intervention in these disease spaces has therefore made the IL-11 signaling axis an attractive target in drug discovery, and antibody inhibitors of IL-11 signaling are currently under evaluation in Phase I/II clinical trials. While lower molecular weight small molecule and peptide inhibitors may offer the potential for improved tissue penetration, developability and manufacturing cost compared with a protein therapeutic, reports of such chemical matter in the literature are limited. In this work, a series of cyclic peptides derived from phage display biopanning campaigns against both IL-11 and its cognate receptor IL-11Rα are presented. The most active IL-11 binder (peptide 4, K
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