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Issue 64, 2015
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A unified approach toward the rational design of selective low nanomolar human neutrophil elastase inhibitors

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Abstract

A computer-aided campaign boosted the discovery of potent human neutrophil elastase (HNE) inhibitors. A pharmacophoric model was developed, validated and applied to filter an oxo-beta-lactam library previously generated by de novo design. This campaign led us to compound 1 which showed an inhibitory activity of 6.9 nM against HNE, more active than the only commercially available HNE inhibitor for therapeutic usage. Computer-aided methodologies proved again to be powerful tools to increase the rate of success for HNE inhibitor discovery either for therapeutic or activity-based probing development.

Graphical abstract: A unified approach toward the rational design of selective low nanomolar human neutrophil elastase inhibitors

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Publication details

The article was received on 28 Apr 2015, accepted on 01 Jun 2015 and first published on 04 Jun 2015


Article type: Paper
DOI: 10.1039/C5RA07783D
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Citation: RSC Adv., 2015,5, 51717-51721
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    A unified approach toward the rational design of selective low nanomolar human neutrophil elastase inhibitors

    L. R. P. Areias, E. F. P. Ruivo, L. M. Gonçalves, M. T. Duarte, V. André, R. Moreira, S. D. Lucas and R. C. Guedes, RSC Adv., 2015, 5, 51717
    DOI: 10.1039/C5RA07783D

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