Halofuginone (RU-19110)

Halofuginone (RU-19110) is the competitively inhibitor of prolyl-tRNA synthetase with Ki of 18.3 nM.It could also down-regulate Smad3 and blocked TGF-β signaling at 10 ng/ml in mammal.

In mammals, halofuginone at 10 ng/ml down-regulates Smad3, blocking TGF-β signaling and preventing both the differentiation of fibroblasts to myofibroblasts and the transitioning of epithelial cells to mesenchymal cells[2].

Halofuginone clearly extends the survival times of the parasite-infected mice. Oral treatment with halofuginone at doses of 0.2 and 1 mg/kg has an apparent curative effect for the infected mice. The subcutaneous administration of 0.2 mg of halofuginone per kg likewise extends the survival times of the infected mice, but none of the mice is cured. The mice in the 5-mg/kg dose groups die before the completion of treatment with the drug either orally or subcutaneously. Subcutaneous treatment with halofuginone appears to be more toxic to mice than oral treatment[3].

[1] Keller TL, et al. Nat Chem Biol. 2012, 8(3):311-317. [2] Nelson EF, et al. Molecular Vision. 2012, 18:479-487. [3] McLaughlin NP, et al. Bioorg Med Chem. 2014, 22(7):1993-2004.