Inhibiting MIFs intrinsic tautomerase activity by the small compound inhibitor ISO-1 reduced proliferation and mitogenic signalling in glioblastoma cells. Small compound inhibitors can block the tautomerase activity of MIF. Incubating LN229 (A) and LN18 (B) cells with increasing concentrations of the inhibitor ISO-1 for 6 h (LN229) or 24 h (LN18) reduced cell proliferation. (* p < 0.05, *** p < 0.0005). Western Blot analysis of Akt and Erk1/2 phosphorylation showed a marked reduction in basal activity after ISO-1 treatment for 6 h in both cell lines (C). Akt and Erk phosphorylation ratios were calculated from two independent experiments.