Abstract
Substituted N-phenylbenzisothiazolones have been investigated as inhibitors of the tautomerase activity of the proinflammatory cytokine MIF (macrophage migration inhibitory factor). Numerous compounds were found to possess antagonist activity in the low micromolar range with the most potent being the 6-hydroxy analog 1w. Compound 1w and the p-cyano analog 1c were also shown to exhibit significant inhibition of the binding of MIF to its transmembrane receptor CD74. Consistently, both compounds were also found to retard the MIF-dependent phosphorylation of ERK1/2 in human synovial fibroblasts.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Differentiation, B-Lymphocyte / metabolism
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Binding Sites
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Cell Line
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Cell Movement / drug effects
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Computer Simulation
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Drug Design
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Histocompatibility Antigens Class II / metabolism
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Humans
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Macrophage Migration-Inhibitory Factors / antagonists & inhibitors*
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Macrophage Migration-Inhibitory Factors / metabolism
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Phosphorylation
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Protein Binding
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Thiazoles / chemical synthesis
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Thiazoles / chemistry*
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Thiazoles / pharmacology
Substances
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Antigens, Differentiation, B-Lymphocyte
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Histocompatibility Antigens Class II
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Macrophage Migration-Inhibitory Factors
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Thiazoles
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invariant chain
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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1,2-benzisothiazoline-3-one