Macrophage migration inhibitory factor antagonists and methods of using same.

Abstract

Methods of inhibiting one or more biol. activities of Macrophage migration inhibitory factor (MIF) polypeptides are provided using an MIF inhibitory compd. The methods include therapeutic methods for treating cancers and inflammatory diseases. In some embodiments, the compds. have a structure of Formula I wherein each R is independently H, halo, OH, alkyl, substituted alkyl, aryl, amino, or carboxyl; R1 is H, halo, OH, alkyl, substituted alkyl, or aryl; R2 is H, halo, OH, alkyl, substituted alkyl, aryl, or amino; and n is an integer from 0 to 5. In some embodiments, the compd. forms a stable interaction with at least a methionine at the second N-terminal residue (Met-2) of the MIF polypeptide. As disclosed herein, MIF biol. activity inhibition can result in indirect inhibition of Hypoxia-inducible Factor 1α (HIF-1α) biol. activity through affects on HIF-1α stability. The presently disclosed subject matter further provides in some embodiments, an antisense polynucleotide comprising a nucleotide sequence having binding specificity for a target sequence from MIF. [on SciFinder(R)]