BP79 is a potent TSLP receptor inhibitor. BP79 disrupts TSLP -mediated ternary complex formation, blocks TSLPR - IL7Rα co-localization, binds and stabilizes TSLPR, and inhibits phosphorylated STAT3/6. BP79 suppresses immune cell infiltration, secretion of IL-13, IL-4. BP79 can be used for the research of inflammation diseases, such as atopic dermatitis, allergic asthma, and allergic rhinitis [1] [2] [3].
In Vitro, BP79 (5-20 µM; 36 h) inhibits TSLP-induced IL-13 (80% inhibition at 20 µM) and IL-4 (60% inhibition at 20 µM) secretion in HuT78 cells in a concentration-dependent manner [1]. BP79 (0.15-20 µM; 36 h) potently inhibits TSLP-induced IL-4 (IC50 = 2.88 µM) and IL-13 (IC50 = 0.97 µM) secretion in primary human CD4+ T cells, with ≥80% inhibition at 10 µM and 20 µM[1]. BP79 (0.15-20 µM; 24 h) shows no significant cytotoxicity at concentrations up to 20 µM in primary human CD4+ T cells, keratinocytes, and fibroblasts, with viability remaining ≥80%[1]. BP79 (20 µM; 1-5 days) abrogates TSLP-mediated hyperproliferation of primary human CD4+ T cells[1]. BP79 (20 µM) inhibits TSLP-induced STAT6 phosphorylation in primary human CD4+ T cells and STAT3 phosphorylation in primary human keratinocytes[1]. BP79 (20 µM; 24 h) inhibits TSLP-induced OX-40L expression and CCL17 secretion in primary human myeloid dendritic cells, and reduces dendritic cell-mediated IL-13 secretion from naive CD4+ T cells[1]. BP79 (20 µM; 10 min) directly interacts with recombinant TSLPR, thermally stabilizing the protein up to 45 °C[1]. BP79 (20 µM; topical; once daily for 4 days) suppresses pro-inflammatory cytokine secretion, restores skin barrier protein expression, inhibits TSLP production, and blocks CD4+ T-cell infiltration in a human atopic diseases multi-organ chip model, with beneficial effects on both skin and lung tissues[1]. BP79 (10 μM) exhibits moderate binding to some kinases, but does not inhibit JAK2/JAK3/TYK2 kinases in the TSLP signaling pathway[2]. BP79 prevents the co-localization of TSLPR and IL-7Rα in primary keratinocytes following TSLP treatment, supporting its targeting of the TSLP signaling pathway[2].
References:
[1]. Adhikary PP, et al. Disrupting TSLP-TSLP receptor interactions via putative small molecule inhibitors yields a novel and efficient treatment option for atopic diseases. EMBO Mol Med. 2024;16(7):1630-1656.
[2]. Christopher Hoang. The development of small molecule inhibitors of thymic stromal lymphopoietin signaling for the treatment of atopic dermatitis. \t University of British Columbia. December 2023.
[3]. Sarah Hedtrich, et al. N1-(3,4-dichlorophenyl)maleamide derivatives and the use thereof in the treatment of inflammatory disorders. WO2025213277A1. 2025-10-16.
In Vitro, BP79 (5-20 µM; 36 h) inhibits TSLP-induced IL-13 (80% inhibition at 20 µM) and IL-4 (60% inhibition at 20 µM) secretion in HuT78 cells in a concentration-dependent manner [1]. BP79 (0.15-20 µM; 36 h) potently inhibits TSLP-induced IL-4 (IC50 = 2.88 µM) and IL-13 (IC50 = 0.97 µM) secretion in primary human CD4+ T cells, with ≥80% inhibition at 10 µM and 20 µM[1]. BP79 (0.15-20 µM; 24 h) shows no significant cytotoxicity at concentrations up to 20 µM in primary human CD4+ T cells, keratinocytes, and fibroblasts, with viability remaining ≥80%[1]. BP79 (20 µM; 1-5 days) abrogates TSLP-mediated hyperproliferation of primary human CD4+ T cells[1]. BP79 (20 µM) inhibits TSLP-induced STAT6 phosphorylation in primary human CD4+ T cells and STAT3 phosphorylation in primary human keratinocytes[1]. BP79 (20 µM; 24 h) inhibits TSLP-induced OX-40L expression and CCL17 secretion in primary human myeloid dendritic cells, and reduces dendritic cell-mediated IL-13 secretion from naive CD4+ T cells[1]. BP79 (20 µM; 10 min) directly interacts with recombinant TSLPR, thermally stabilizing the protein up to 45 °C[1]. BP79 (20 µM; topical; once daily for 4 days) suppresses pro-inflammatory cytokine secretion, restores skin barrier protein expression, inhibits TSLP production, and blocks CD4+ T-cell infiltration in a human atopic diseases multi-organ chip model, with beneficial effects on both skin and lung tissues[1]. BP79 (10 μM) exhibits moderate binding to some kinases, but does not inhibit JAK2/JAK3/TYK2 kinases in the TSLP signaling pathway[2]. BP79 prevents the co-localization of TSLPR and IL-7Rα in primary keratinocytes following TSLP treatment, supporting its targeting of the TSLP signaling pathway[2].
References:
[1]. Adhikary PP, et al. Disrupting TSLP-TSLP receptor interactions via putative small molecule inhibitors yields a novel and efficient treatment option for atopic diseases. EMBO Mol Med. 2024;16(7):1630-1656.
[2]. Christopher Hoang. The development of small molecule inhibitors of thymic stromal lymphopoietin signaling for the treatment of atopic dermatitis. \t University of British Columbia. December 2023.
[3]. Sarah Hedtrich, et al. N1-(3,4-dichlorophenyl)maleamide derivatives and the use thereof in the treatment of inflammatory disorders. WO2025213277A1. 2025-10-16.