Therapeutics: Macrophage migration inhibitory factor (MIF); CD74

In vitro studies suggest biaryltriazole-based MIF inhibitors could help treat autoimmune diseases and cancer that involve MIF. Previous studies suggested targeting tautomerase sites on MIF can disrupt MIF-CD74 interactions that lead to pro-inflammatory cytokine production. Crystallographic studies, computational modeling, chemical synthesis and in vitro testing identified several biaryltriazole analogs that inhibited MIF tautomerase activity with Ki <100 nM. Next steps include testing the analogs in rodents.

Kyorin Pharmaceutical Co. Ltd. markets Ketas ibudilast, an inhibitor of MIF and phosphodiesterase-4 (PDE-4), to treat asthma. Kyorin and Medicova Inc. market the compound to treat stroke and have it in Phase II testing for autoimmune and neurological indications...