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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 K. ; 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
; ; ; ; ; ; ; ; and
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 (ACS)
external identifiers
  • scopus:84986579038
  • pmid:27500311
  • wos:000383111300032
ISSN
0022-2623
DOI
10.1021/acs.jmedchem.6b00957
language
English
LU publication?
yes
id
05dd2407-2656-40e2-a26f-97b18cbfd652
alternative location
https://pubs.acs.org/doi/10.1021/acs.jmedchem.6b00957
date added to LUP
2016-10-03 16:07:42
date last changed
2024-04-19 09:47:24
@article{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 K. 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    = {{The American Chemical Society (ACS)}},
  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}},
  doi          = {{10.1021/acs.jmedchem.6b00957}},
  volume       = {{59}},
  year         = {{2016}},
}