title: MIF as a disease target: ISO-1 as a proof-of-concept therapeutic.
abstract: Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory cytokine that has been implicated as playing a causative role in many disease states, including sepsis, pneumonia, diabetes, rheumatoid arthritis, inflammatory bowel disease, psoriasis and cancer. To inhibit the enzymatic and biologic activities of MIF, we and others have developed small-molecule MIF inhibitors. Most MIF inhibitors bind within the hydrophobic pocket that contains highly conserved amino acids known to be essential for MIF's proinflammatory activity. The best characterized of these small-molecule MIF inhibitors, (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) has been validated in scores of laboratories worldwide. Like neutralizing anti-MIF antibodies, ISO-1 significantly improves survival and reduces disease progression and/or severity in multiple murine models where MIF is implicated. This MIF inhibitor, its derivatives and other MIF-targeted compounds show great promise for future testing in disease states where increased MIF activity has been discovered.
authors.affiliation: Department of Medicinal Chemistry, The Feinstein Institute for Medical Research, North Shore/LIJ Health System, Manhasset, NY 11030, USA. yalabed@nshs.edu
authors.forename: Yousef
authors.initials: Y
authors.lastname: Al-Abed
authors.forename: Sonya
authors.initials: S
authors.lastname: VanPatten
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology*; D008958:Models, Molecular; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D054852:Small Molecule Libraries