Format

Send to

Choose Destination
J Med Chem. 2005 Aug 25;48(17):5415-8.

The protein farnesyltransferase inhibitor Tipifarnib as a new lead for the development of drugs against Chagas disease.

Author information

1
Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.

Abstract

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.

PMID:
16107140
PMCID:
PMC3265986
DOI:
10.1021/jm050441z
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center