Neutrophil Elastase as a Target in Lung Cancer

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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Neutrophil Elastase as a Target in Lung Cancer



Anti-Cancer Agents in Medicinal Chemistry, 12(6): 565-579.

Author(s): Gautier Moroy, Alain J.P. Alix, Janos Sapi, William Hornebeck and Erika Bourguet.

Affiliation: Universite de Reims Champagne- Ardenne, Faculte des Sciences, IFR53 Biomolecules, Laboratoire de Spectroscopies et Structures Biomoleculaires (LSSBM, EA 4303) BP 1039, 51687 Reims Cedex2, France.

Abstract

Human neutrophil elastase (HNE), a main actor in the development of chronic obstructive pulmonary diseases, has been recently involved in non-small cell lung cancer progression. It can act at several levels (i) intracellularly, cleaving for instance the adaptor molecule insulin receptor substrate-1 (IRS-1) (ii) at the cell surface, hydrolyzing receptors as CD40 (iii) in the extracellular space, generating elastin fragments i.e. morphoelastokines which potently stimulate cancer cell invasiveness and angiogenesis.

Since decades, researchers identified natural compounds and/or synthesized agents which antagonize HNE activity that will be described in this review article. Some of these compounds might be of value as therapeutic agents in lung cancer. However, it is now widely accepted that lung tumor invasion and metastasis involve proteolytic cascades. Accordingly, we will here mainly focus our attention to natural substances able to display a dual inhibitory capacity (i.e. lipids and derivatives, phenolics) towards HNE and matrix metalloproteinases (MMPs), particularly MMP-2. To that purpose, we recently synthesize substances named “LipoGalardin” (Moroy G. et al., Biochem. Pharmacol., 2011, 81(5), 626-635) exhibiting such inhibitory bifunctionality. At last, we will propose an original synthetic scheme for designing a potent biheaded HNE/MMP-2 inhibitor.


Keywords:

Neutrophil Elastase, Lung cancer, (Dual) inhibitors, Bifunctionality.



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Article Details

Volume: 12
Issue Number: 6
First Page: 565
Last Page: 579
Page Count: 15
DOI: 10.2174/187152012800617696
Price: $58
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