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Visualization of assay results on STB compounds.

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posted on 2024-02-20, 18:40 authored by Franz S. Gruber, Anthony Richardson, Zoe C. Johnston, Rachel Myles, Neil R. Norcross, David P. Day, Irene Georgiou, Laura Sesma-Sanz, Caroline Wilson, Kevin D. Read, Sarah Martins da Silva, Christopher L. R. Barratt, Ian H. Gilbert, Jason R. Swedlow

(A) Heatmap showing standardized results (z-score) for every Toolbox compound screened at 30 μM in selected assays: Acrosome 2 (3h with compound then induction with acrosome reaction using an agonist mix), Motility Hyperactive (30 min capacitation then 30 min incubation with compound), Motility Progressive (3h incubation with compounds under non-capacitating conditions), Motility Total (3h incubation with compound under non-capacitating conditions)), Solubility (aqueous solubility of compounds after 24h incubation), Sperm viability (3h with compound then propidium iodide assay), Toxicity HeLa (24h compound incubation then cell painting assay), Toxicity HepG2 (70h incubation with compound then resaruzin based assay). Heatmap color indicates decrease (blue) or increase (red). (B) UMAP plot showing groups of compounds with similar assay profile. Color indicates annotated sperm function. (C) Structures and zoom-in of three compounds with related structures described to modulate LRRK2 kinase but appear to have different effects on sperm function.

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