49 research outputs found

    AI is a viable alternative to high throughput screening: a 318-target study

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    : High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

    Targeting Mast Cells in Allergic Disease: Current Therapies and Drug Repurposing

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    The incidence of allergic disease has grown tremendously in the past three generations. While current treatments are effective for some, there is considerable unmet need. Mast cells are critical effectors of allergic inflammation. Their secreted mediators and the receptors for these mediators have long been the target of allergy therapy. Recent drugs have moved a step earlier in mast cell activation, blocking IgE, IL-4, and IL-13 interactions with their receptors. In this review, we summarize the latest therapies targeting mast cells as well as new drugs in clinical trials. In addition, we offer support for repurposing FDA-approved drugs to target mast cells in new ways. With a multitude of highly selective drugs available for cancer, autoimmunity, and metabolic disorders, drug repurposing offers optimism for the future of allergy therapy

    Law and COVID-19

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    Additional file 28 of Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

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    Additional file 28: Table S18. Sex-participation association of the variants with significant sex-specific lipid results

    Additional file 17 of Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

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    Additional file 17: Table S9. PheWAS UKB-MVP meta-analysis results for each index lipid variant at Bonferroni threshold for multiple testing

    Additional file 5 of Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

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    Additional file 5: Table S4. Frequency of lipid-related publications for the PoPS+ prioritized genes
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