Investigating Polypharmacology through Targeting Known Human Neutrophil Elastase Inhibitors to Proteinase 3
Gartan, Parveen; Khorsand, Fahimeh; Mizar, Pushpak; Vahokoski, Juha; Cervantes, Luis F.; Haug, Bengt Erik; Brenk, Ruth; Brooks, Charles L.; Reuter, Nathalie
Journal article, Peer reviewed
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https://hdl.handle.net/11250/3144348Utgivelsesdato
2024Metadata
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- Department of Chemistry [442]
- Registrations from Cristin [10149]
Originalversjon
Journal of Chemical Information and Modeling. 2024, 64 (3), 621-626. 10.1021/acs.jcim.3c01949Sammendrag
Using a combination of multisite λ−dynamics (MSλD) together with in vitro IC50 assays, we evaluated the polypharmacological potential of a scaffold currently in clinical trials for inhibition of human neutrophil elastase (HNE), targeting cardiopulmonary disease, for efficacious inhibition of Proteinase 3 (PR3), a related neutrophil serine proteinase. The affinities we observe suggest that the dihydropyrimidinone scaffold can serve as a suitable starting point for the establishment of polypharmacologically targeting both enzymes and enhancing the potential for treatments addressing diseases like chronic obstructive pulmonary disease.