Imperial College London
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ProfessorRobertSnelgrove

Faculty of Medicine, National Heart & Lung Institute

Professor of Respiratory Science
 
 
 
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Contact

 

+44 (0)20 7594 8192robert.snelgrove

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Low:2017:10.1038/srep44449,
author = {Low, CM and Akthar, S and Patel, D and Loeser, S and Wong, C and Jackson, P and Blalock, JE and Hare, S and Lloyd, C and Snelgrove, RJ},
doi = {10.1038/srep44449},
journal = {Scientific Reports},
title = {The development of novel LTA4H modulators to selectively target LTB4 generation},
url = {http://dx.doi.org/10.1038/srep44449},
volume = {7},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The pro-inflammatory mediator leukotriene B4 (LTB4) is implicated in the pathologies of an array of diseases and thus represents an attractive therapeutic target. The enzyme leukotriene A4 hydrolase (LTA4H) catalyses the distal step in LTB4 synthesis and hence inhibitors of this enzyme have been actively pursued. Despite potent LTA4H inhibitors entering clinical trials all have failed to show efficacy. We recently identified a secondary anti-inflammatory role for LTA4H in degrading the neutrophil chemoattractant Pro-Gly-Pro (PGP) and rationalized that the failure of conventional LTA4H inhibitors may be that they inadvertently prevented PGP degradation. We demonstrate that these inhibitors do indeed fail to discriminate between the dual activities of LTA4H, and enable PGP accumulation in mice. Accordingly, we have developed novel compounds that potently inhibit LTB4 generation whilst leaving PGP degradation unperturbed. These novel compounds could represent a safer and superior class of LTA4H inhibitors for translation into the clinic.
AU  - Low,CM
AU  - Akthar,S
AU  - Patel,D
AU  - Loeser,S
AU  - Wong,C
AU  - Jackson,P
AU  - Blalock,JE
AU  - Hare,S
AU  - Lloyd,C
AU  - Snelgrove,RJ
DO  - 10.1038/srep44449
PY  - 2017///
SN  - 2045-2322
TI  - The development of novel LTA4H modulators to selectively target LTB4 generation
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/srep44449
UR  - http://hdl.handle.net/10044/1/44416
VL  - 7
ER  -
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