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Tipifarnib (R115777) is a highly potent inhibitor of Trypanosoma cruzi growth (ED50 = 4 nM) due to the inhibition of cytochrome P450 sterol 14-demethylase (CYP51).
Tipifarnib demonstrates potent in vitro inhibition of Trypanosoma cruzi growth via CYP51 inhibition, providing a lead for Chagas disease drug development.
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May support tipifarnib repurposing for Chagas disease; leaves open translation of in vitro potency to in vivo efficacy.
Tipifarnib (R115777), an inhibitor of human protein farnesyltransferase (PFT), is shown to be a highly potent inhibitor of Trypanosoma cruzi growth (ED(50) = 4 nM). Surprisingly, this is due to the inhibition of cytochrome P450 sterol 14-demethylase (CYP51, EC 1.14.13.70). Homology models of the T. cruzi CYP51 were used for the prediction of the binding modes of the substrate lanosterol and of Tipifarnib, providing a basis for the design of derivatives with selectivity for TcCYP51 over human PFT.
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Hucke et al. (2005) studied Chagas Disease. Tipifarnib (R115777) was evaluated on Trypanosoma cruzi growth inhibition (ED50 = 4 nM). Tipifarnib (R115777) is a highly potent inhibitor of Trypanosoma cruzi growth (ED50 = 4 nM) due to the inhibition of cytochrome P450 sterol 14-demethylase (CYP51).
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