You want to bet that AI will eventually help to lengthen a healthier human life? This is only the beginning!
"... artificial intelligence (AI) to discover novel senolytic compounds, a class of small molecules under intense study for their ability to suppress age-related processes such as fibrosis, inflammation and cancer. ...
describes the AI-guided screening of more than 800,000 compounds to reveal three drug candidates with comparable efficacy and superior medicinal chemistry properties than those of senolytics currently under investigation. ..."
describes the AI-guided screening of more than 800,000 compounds to reveal three drug candidates with comparable efficacy and superior medicinal chemistry properties than those of senolytics currently under investigation. ..."
From the abstract:
"The accumulation of senescent cells is associated with aging, inflammation and cellular dysfunction. Senolytic drugs can alleviate age-related comorbidities by selectively killing senescent cells. Here we screened 2,352 compounds for senolytic activity in a model of etoposide-induced senescence and trained graph neural networks to predict the senolytic activities of >800,000 molecules. Our approach enriched for structurally diverse compounds with senolytic activity; of these, three drug-like compounds selectively target senescent cells across different senescence models, with more favorable medicinal chemistry properties than, and selectivity comparable to, those of a known senolytic, ABT-737. Molecular docking simulations of compound binding to several senolytic protein targets, combined with time-resolved fluorescence energy transfer experiments, indicate that these compounds act in part by inhibiting Bcl-2, a regulator of cellular apoptosis. We tested one compound, BRD-K56819078, in aged mice and found that it significantly decreased senescent cell burden and mRNA expression of senescence-associated genes in the kidneys. Our findings underscore the promise of leveraging deep learning to discover senotherapeutics."
Discovering small-molecule senolytics with deep neural networks (no public access)
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