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Investigating Polypharmacology through Targeting Known Human Neutrophil Elastase Inhibitors to Proteinase 3. | LitMetric

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Article Abstract

Using a combination of multisite λ-dynamics (MSλD) together with IC 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10865350PMC
http://dx.doi.org/10.1021/acs.jcim.3c01949DOI Listing

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