Investigating Polypharmacology Through Targeting Known Human Neutrophil Elastase Inhibitors to Proteinase 3

Overview

Journal J Chem Inf Model

Publisher American Chemical Society

Specialties Chemistry
Medical Informatics

Date 2024 Jan 26

PMID 38276895

Authors

Parveen Gartan

Fahimeh Khorsand

Pushpak Mizar

Juha Ilmari Vahokovski

Luis F Cervantes

Bengt Erik Haug

Ruth Brenk

Charles L Brooks 3rd

Nathalie Reuter

Affiliations

Soon will be listed here.

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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