@article{
author = "Vujičić, Milica and Nikolić, Ivana and Krajnović, Tamara and Cheng, Kai-Fan and VanPatten, Sonya and He, Mingzhu and Stošić-Grujičić, Stanislava and Stojanović, Ivana D. and Al-Abed, Yousef and Saksida, Tamara",
year = "2014",
abstract = "Macrophage migration inhibitory factor is a multifunctional cytokine
involved in the regulation of immune processes and also in apoptosis
induction. Elevated MIF expression is detrimental for insulin-producing
beta cells and MIF inhibition protected beta cells from several
cytotoxic insults such as inflammatory cytokines, high fatty acids or
high glucose concentrations. Therefore, the aim of this study was to
investigate two newly synthesized small molecule MIF inhibitors (K664-1
and K647-1) and to compare them with previously established effects of
the prototypical MIF inhibitor, ISO-1. Our results indicate that K664-1
and K647-1 are 160- and 40-fold more effective in inhibition of MIF's
tautomerase activity than ISO-1. Also, new inhibitors confer beta cell
protection from cytokine-triggered apoptosis at significantly lower
concentrations than LSO-1. Although all three MIF inhibitors inhibit
caspase 3 activity, K664-1 and K647-1 suppress pro-apoptotic BAX protein
expression and up-regulate anti-apoptotic Bcl-2 mRNA. Finally, all three
MIF inhibitors operate through blockade of nitric oxide production
stimulated by cytokines. In conclusion, two novel MIF inhibitors are
more potent than ISO-1 and operate through inhibition of the
mitochondria-related apoptotic pathway. We propose that these compounds
represent a unique class of anti-MIF antagonists that should be further
tested for therapeutic use. (C) 2014 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmacology",
title = "Novel inhibitors of macrophage migration inhibitory factor prevent
cytokine-induced beta cell death",
volume = "740",
doi = "10.1016/j.ejphar.2014.06.009",
pages = "683-689"
}