Literature DB >> 16107140

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

Oliver Hucke1, Michael H Gelb, Christophe L M J Verlinde, Frederick S Buckner.   

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.

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Year:  2005        PMID： 16107140      PMCID： PMC3265986          DOI： 10.1021/jm050441z

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  16 in total

1.  Crystal structure of cytochrome P450 14alpha -sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors.

Authors:  L M Podust; T L Poulos; M R Waterman
Journal:  Proc Natl Acad Sci U S A       Date:  2001-03-13       Impact factor: 11.205

2.  A three-dimensional model of lanosterol 14alpha-demethylase of Candida albicans and its interaction with azole antifungals.

Authors:  H Ji; W Zhang; Y Zhou; M Zhang; J Zhu; Y Song; J Lü
Journal:  J Med Chem       Date:  2000-06-29       Impact factor: 7.446

3.  Substrate recognition sites in 14alpha-sterol demethylase from comparative analysis of amino acid sequences and X-ray structure of Mycobacterium tuberculosis CYP51.

Authors:  L M Podust; J Stojan; T L Poulos; M R Waterman
Journal:  J Inorg Biochem       Date:  2001-12-15       Impact factor: 4.155

4.  QXP: powerful, rapid computer algorithms for structure-based drug design.

Authors:  C McMartin; R S Bohacek
Journal:  J Comput Aided Mol Des       Date:  1997-07       Impact factor: 3.686

5.  Comparative protein modelling by satisfaction of spatial restraints.

Authors:  A Sali; T L Blundell
Journal:  J Mol Biol       Date:  1993-12-05       Impact factor: 5.469

6.  Estriol bound and ligand-free structures of sterol 14alpha-demethylase.

Authors:  Larissa M Podust; Liudmila V Yermalitskaya; Galina I Lepesheva; Vladimir N Podust; Enrique A Dalmasso; Michael R Waterman
Journal:  Structure       Date:  2004-11       Impact factor: 5.006

7.  A phase I trial and pharmacokinetic study of tipifarnib, a farnesyltransferase inhibitor, and tamoxifen in metastatic breast cancer.

Authors:  Peter F Lebowitz; Jennifer Eng-Wong; Brigitte C Widemann; Frank M Balis; Nalini Jayaprakash; Catherine Chow; Geoff Clark; Susan B Gantz; David Venzon; JoAnne Zujewski
Journal:  Clin Cancer Res       Date:  2005-02-01       Impact factor: 12.531

8.  CYP51 from Trypanosoma brucei is obtusifoliol-specific.

Authors:  Galina I Lepesheva; W David Nes; Wenxu Zhou; George C Hill; Michael R Waterman
Journal:  Biochemistry       Date:  2004-08-24       Impact factor: 3.162

9.  Phase II study of R115777, a farnesyl transferase inhibitor, in myelodysplastic syndrome.

Authors:  Razelle Kurzrock; Maher Albitar; Jorge E Cortes; Elihu H Estey; Stefan H Faderl; Guillermo Garcia-Manero; Deborah A Thomas; Francis J Giles; Mary Ellen Ryback; Alain Thibault; P De Porre; Hagop M Kantarjian
Journal:  J Clin Oncol       Date:  2004-04-01       Impact factor: 44.544

10.  Crystal structures of the anticancer clinical candidates R115777 (Tipifarnib) and BMS-214662 complexed with protein farnesyltransferase suggest a mechanism of FTI selectivity.

Authors:  T Scott Reid; Lorena S Beese
Journal:  Biochemistry       Date:  2004-06-08       Impact factor: 3.162
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  29 in total

1.  Pharmacological characterization, structural studies, and in vivo activities of anti-Chagas disease lead compounds derived from tipifarnib.

Authors:  Frederick S Buckner; Maria Terezinha Bahia; Praveen Kumar Suryadevara; Karen L White; David M Shackleford; Naveen Kumar Chennamaneni; Matthew A Hulverson; Joy U Laydbak; Eric Chatelain; Ivan Scandale; Christophe L M J Verlinde; Susan A Charman; Galina I Lepesheva; Michael H Gelb
Journal:  Antimicrob Agents Chemother       Date:  2012-07-09       Impact factor: 5.191

2.  Structurally simple inhibitors of lanosterol 14alpha-demethylase are efficacious in a rodent model of acute Chagas disease.

Authors:  Praveen Kumar Suryadevara; Srinivas Olepu; Jeffrey W Lockman; Junko Ohkanda; Mandana Karimi; Christophe L M J Verlinde; James M Kraus; Jan Schoepe; Wesley C Van Voorhis; Andrew D Hamilton; Frederick S Buckner; Michael H Gelb
Journal:  J Med Chem       Date:  2009-06-25       Impact factor: 7.446

3.  X-ray structure of 4,4'-dihydroxybenzophenone mimicking sterol substrate in the active site of sterol 14alpha-demethylase (CYP51).

Authors:  Ali Nasser Eddine; Jens P von Kries; Mikhail V Podust; Thulasi Warrier; Stefan H E Kaufmann; Larissa M Podust
Journal:  J Biol Chem       Date:  2008-03-26       Impact factor: 5.157

4.  Dialkylimidazole inhibitors of Trypanosoma cruzi sterol 14α-demethylase as anti-Chagas disease agents.

Authors:  Praveen Kumar Suryadevara; Kishore Kumar Racherla; Srinivas Olepu; Neil R Norcross; Hari Babu Tatipaka; Jennifer A Arif; Joseph D Planer; Galina I Lepesheva; Christophe L M J Verlinde; Frederick S Buckner; Michael H Gelb
Journal:  Bioorg Med Chem Lett       Date:  2013-08-12       Impact factor: 2.823

Review 5.  Targeting Trypanosoma cruzi sterol 14α-demethylase (CYP51).

Authors:  Galina I Lepesheva; Fernando Villalta; Michael R Waterman
Journal:  Adv Parasitol       Date:  2011       Impact factor: 3.870

6.  Recent Developments in Sterol 14-demethylase Inhibitors for Chagas Disease.

Authors:  Frederick S Buckner; Julio A Urbina
Journal:  Int J Parasitol Drugs Drug Resist       Date:  2012-12       Impact factor: 4.077

7.  Rational modification of a candidate cancer drug for use against Chagas disease.

Authors:  James M Kraus; Christophe L M J Verlinde; Mandana Karimi; Galina I Lepesheva; Michael H Gelb; Frederick S Buckner
Journal:  J Med Chem       Date:  2009-03-26       Impact factor: 7.446

8.  Complexes of Trypanosoma cruzi sterol 14α-demethylase (CYP51) with two pyridine-based drug candidates for Chagas disease: structural basis for pathogen selectivity.

Authors:  Tatiana Y Hargrove; Zdzislaw Wawrzak; Paul W Alexander; Jason H Chaplin; Martine Keenan; Susan A Charman; Catherine J Perez; Michael R Waterman; Eric Chatelain; Galina I Lepesheva
Journal:  J Biol Chem       Date:  2013-09-18       Impact factor: 5.157

9.  Antitrypanosomal lead discovery: identification of a ligand-efficient inhibitor of Trypanosoma cruzi CYP51 and parasite growth.

Authors:  Grasiella Andriani; Emanuele Amata; Joel Beatty; Zeke Clements; Brian J Coffey; Gilles Courtemanche; William Devine; Jessey Erath; Cristin E Juda; Zdzislaw Wawrzak; Jodianne T Wood; Galina I Lepesheva; Ana Rodriguez; Michael P Pollastri
Journal:  J Med Chem       Date:  2013-03-13       Impact factor: 7.446

Review 10.  New, improved treatments for Chagas disease: from the R&D pipeline to the patients.

Authors:  Isabela Ribeiro; Ann-Marie Sevcsik; Fabiana Alves; Graciela Diap; Robert Don; Michael O Harhay; Shing Chang; Bernard Pecoul
Journal:  PLoS Negl Trop Dis       Date:  2009-07-07
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