ArticleNaunyn-Schmiedeberg's archives of pharmacology2026
In silico and in vitro investigations of novel Siglec-1 inhibitors in a microglial cell model.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
6 authors.
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Abstract
The purpose of this study was to examine the differences which exist between murine, human, and rat Siglec-1, then to research novel inhibitors and assess applicability of HAPI cells to study Siglec-1. Using molecular modelling software, amino acid sequences were analysed for differences across orthologs. Compound library screening of human Siglec-1 was performed, 9 compounds of interest were identified, and 4 were included additionally out of clinical interest. Rational structure activity analysis was conducted on orthologs and chosen compounds. Competitive inhibition enzyme-linked immunosorbent assay (ELISA) using Siglec-1 was used on these 13 chosen compounds. This was followed by lipopolysaccharide (LPS) treatment of HAPI cells and Siglec-1 detection ELISA to confirm upregulation of Siglec-1. All 13 compounds were analysed using resazurin in HAPI cells with and without treatment of LPS. The N-terminal of murine Siglec-1 varies by approximately by 22% and 11% compared to human and rat orthologs respectively. Murine Siglec-1 includes Leu107 while rat and human share the more polar Ser107, despite a highly similar structure overall. Four compounds showed definable IC
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