Synergistic Machine Learning Accelerated Discovery of Nanoporous Inorganic Crystals as Non-Absorbable Oral Drugs.
Adv Mater
; : e2404688, 2024 May 30.
Article
em En
| MEDLINE
| ID: mdl-38815983
ABSTRACT
Machine learning (ML) has taken drug discovery to new heights, where effective ML training requires vast quantities of high-quality experimental data as input. Non-absorbable oral drugs (NODs) have unique safety advantage for chronic diseases due to their zero systemic exposure, but their empirical discovery is still time-consuming and costly. Here, a synergistic ML method, integrating small data-driven multi-layer unsupervised learning, in silico quantum-mechanical computations, and minimal wet-lab experiments is devised to identify the finest NODs from massive inorganic materials to achieve multi-objective function (high selectivity, large capacity, and stability). Based on this method, a NH4-form nanoporous zeolite with merlinoite (MER) framework (NH4-MER) is discovered for the treatment of hyperkalemia. In three different animal models, NH4-MER shows a superior safety and efficacy profile in reducing blood K+ without Na+ release, which is an unmet clinical need in chronic kidney disease and Gordon's syndrome. This work provides a synergistic ML method to accelerate the discovery of NODs and other shape-selective materials.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Adv Mater
Ano de publicação:
2024
Tipo de documento:
Article