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A Selective Galactose-Coumarin-Derived Galectin-3 Inhibitor Demonstrates Involvement of Galectin-3-glycan Interactions in a Pulmonary Fibrosis Model

Rajput, Vishal Kumar; MacKinnon, Alison; Mandal, Santanu LU ; Collins, Patrick; Blanchard, Helen; Leffler, Hakon LU ; Sethi, Tariq; Schambye, Hans; Mukhopadhyay, Balaram and Nilsson, Ulf J. LU (2016) In Journal of Medicinal Chemistry 59(17). p.8141-8147
Abstract

Synthesis of doubly 3-O-coumarylmethyl-substituted thiodigalactosides from bis-3-O-propargyl-thiodigalactoside resulted in highly selective and high affinity galectin-3 inhibitors. Mutant studies, structural analysis, and molecular modeling revealed that the coumaryl substituents stack onto arginine side chains. One inhibitor displayed efficacy in a murine model of bleomycin-induced lung fibrosis similar to that of a known nonselective galectin-1/galectin-3 inhibitor, which strongly suggests that blocking galectin-3 glycan recognition is an important antifibrotic drug target.

Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Medicinal Chemistry
volume
59
issue
17
pages
7 pages
publisher
The American Chemical Society
external identifiers
  • Scopus:84986579038
ISSN
0022-2623
DOI
10.1021/acs.jmedchem.6b00957
language
English
LU publication?
yes
id
05dd2407-2656-40e2-a26f-97b18cbfd652
date added to LUP
2016-10-03 16:07:42
date last changed
2016-11-08 08:43:12
@misc{05dd2407-2656-40e2-a26f-97b18cbfd652,
  abstract     = {<p>Synthesis of doubly 3-O-coumarylmethyl-substituted thiodigalactosides from bis-3-O-propargyl-thiodigalactoside resulted in highly selective and high affinity galectin-3 inhibitors. Mutant studies, structural analysis, and molecular modeling revealed that the coumaryl substituents stack onto arginine side chains. One inhibitor displayed efficacy in a murine model of bleomycin-induced lung fibrosis similar to that of a known nonselective galectin-1/galectin-3 inhibitor, which strongly suggests that blocking galectin-3 glycan recognition is an important antifibrotic drug target.</p>},
  author       = {Rajput, Vishal Kumar and MacKinnon, Alison and Mandal, Santanu and Collins, Patrick and Blanchard, Helen and Leffler, Hakon and Sethi, Tariq and Schambye, Hans and Mukhopadhyay, Balaram and Nilsson, Ulf J.},
  issn         = {0022-2623},
  language     = {eng},
  month        = {09},
  number       = {17},
  pages        = {8141--8147},
  publisher    = {ARRAY(0x7c82728)},
  series       = {Journal of Medicinal Chemistry},
  title        = {A Selective Galactose-Coumarin-Derived Galectin-3 Inhibitor Demonstrates Involvement of Galectin-3-glycan Interactions in a Pulmonary Fibrosis Model},
  url          = {http://dx.doi.org/10.1021/acs.jmedchem.6b00957},
  volume       = {59},
  year         = {2016},
}