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

ABSTRACT: 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.

SUBMITTER: Gartan P 

PROVIDER: S-EPMC10865350 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature