title: Benzisothiazolones as modulators of macrophage migration inhibitory factor.
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.
authors: Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA. william.jorgensen@yale.edu
authors: William L
authors: WL
authors: Jorgensen
authors: Alexander
authors: A
authors: Trofimov
authors: Xin
authors: X
authors: Du
authors: Alissa A
authors: AA
authors: Hare
authors: Lin
authors: L
authors: Leng
authors: Richard
authors: R
authors: Bucala
mesh_terms: D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003198:Computer Simulation; D015195:Drug Design; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; D013844:Thiazoles; C045084:invariant chain; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C015699:1,2-benzisothiazoline-3-one