J Med Chem. 2007 Jul 12;50(14):3274-82. Epub 2007 Jun 8.

Synthesis, biochemical, and cellular evaluation of farnesyl monophosphate prodrugs as farnesyltransferase inhibitors.

Clark MK, Scott SA, Wojtkowiak J, Chirco R, Mathieu P, Reiners JJ Jr, Mattingly RR, Borch RF, Gibbs RA.

Source

Medicinal Chemistry and Molecular Pharmacology and Cancer Center, Purdue University, West Lafayette, Indiana 47907, USA.

Abstract

Certain farnesyl diphosphate (FPP) analogs are potent inhibitors of the potential anticancer drug target protein farnesyltransferase (FTase), but these compounds are not suitable as drug candidates. Thus, phosphoramidate prodrug derivatives of the monophosphate precursors of FPP-based FTase inhibitors have been synthesized. The monophosphates themselves were significantly more potent inhibitors of FTase than the corresponding FPP analogs. The effects of the prodrug 5b (a derivative of 3-allylfarnesyl monophosphate) have been evaluated on prenylation of RhoB and on the cell cycle in a human malignant schwannoma cell line (STS-26T). In combination treatments, 1-3 microM 5b plus 1 microM lovastatin induced a significant inhibition of RhoB prenylation, and a combination of these drugs at 1 microM each also resulted in significant cell cycle arrest in G1. Indeed, combinations as low as 50 nM lovastatin + 1 microM 5c or 250 nM lovastatin + 50 nM 5c were highly cytostatic in STS-26T cell culture.

PMID:: 17555307; [PubMed - indexed for MEDLINE]

LinkOut - more resources

Full Text Sources

Other Literature Sources

COS Scholar Universe

Supplemental Content

Related citations

Synthesis of imidazole-containing analogues of farnesyl pyrophosphate and evaluation of their biological activity on protein farnesyltransferase. [J Enzyme Inhib Med Chem. 2009]
Synthesis of imidazole-containing analogues of farnesyl pyrophosphate and evaluation of their biological activity on protein farnesyltransferase.
Coudray L, de Figueiredo RM, Duez S, Cortial S, Dubois J. J Enzyme Inhib Med Chem. 2009 Aug; 24(4):972-85.
Synthesis and biochemical evaluation of 3,7-disubstituted farnesyl diphosphate analogues. [J Org Chem. 2008]
Synthesis and biochemical evaluation of 3,7-disubstituted farnesyl diphosphate analogues.
Rawat DS, Krzysiak AJ, Gibbs RA. J Org Chem. 2008 Mar 7; 73(5):1881-7. Epub 2008 Jan 29.
J-104,871, a novel farnesyltransferase inhibitor, blocks Ras farnesylation in vivo in a farnesyl pyrophosphate-competitive manner. [Mol Pharmacol. 1998]
J-104,871, a novel farnesyltransferase inhibitor, blocks Ras farnesylation in vivo in a farnesyl pyrophosphate-competitive manner.
Yonemoto M, Satoh T, Arakawa H, Suzuki-Takahashi I, Monden Y, Kodera T, Tanaka K, Aoyama T, Iwasawa Y, Kamei T, et al. Mol Pharmacol. 1998 Jul; 54(1):1-7.
Review Farnesyltransferase inhibitors: a detailed chemical view on an elusive biological problem. [Curr Med Chem. 2008]
Review Farnesyltransferase inhibitors: a detailed chemical view on an elusive biological problem.
Sousa SF, Fernandes PA, Ramos MJ. Curr Med Chem. 2008; 15(15):1478-92.
Review Non-peptidic prenyltransferase inhibitors: diverse structural classes and surprising anti-cancer mechanisms. [Curr Med Chem. 2001]
Review Non-peptidic prenyltransferase inhibitors: diverse structural classes and surprising anti-cancer mechanisms.
Gibbs RA, Zahn TJ, Sebolt-Leopold JS. Curr Med Chem. 2001 Oct; 8(12):1437-65.

See reviews... See all...

Cited by 2 PubMed Central articles

Working together: Farnesyl transferase inhibitors and statins block protein prenylation. [Mol Cell Pharmacol. 2009]
Working together: Farnesyl transferase inhibitors and statins block protein prenylation.
Wojtkowiak JW, Gibbs RA, Mattingly RR. Mol Cell Pharmacol. 2009 Jan 1; 1(1):1-6.
A novel geranylgeranyl transferase inhibitor in combination with lovastatin inhibits proliferation and induces autophagy in STS-26T MPNST cells. [J Pharmacol Exp Ther. 2010]
A novel geranylgeranyl transferase inhibitor in combination with lovastatin inhibits proliferation and induces autophagy in STS-26T MPNST cells.
Sane KM, Mynderse M, Lalonde DT, Dean IS, Wojtkowiak JW, Fouad F, Borch RF, Reiners JJ Jr, Gibbs RA, Mattingly RR. J Pharmacol Exp Ther. 2010 Apr; 333(1):23-33. Epub 2010 Jan 19.

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
BioAssay
PubChem BioAssay experiments on the biological activities of small molecules that cite the current articles. The depositors of BioAssay data provide these references.
Compound (MeSH Keyword)
PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Synthesis, biochemical, and cellular evaluation of farnesyl monophosphate prodru...
Synthesis, biochemical, and cellular evaluation of farnesyl monophosphate prodrugs as farnesyltransferase inhibitors.
J Med Chem. 2007 Jul 12 ;50(14):3274-82. Epub 2007 Jun 8 .

PubMed
Check Sample Abstracts.
Check Sample Abstracts.
Am J Clin Pathol. 2009 Feb;131(2):286-299.

PubMed
Mucinous cystadenocarcinoma of the breast coexisting with infiltrating ductal ca...
Mucinous cystadenocarcinoma of the breast coexisting with infiltrating ductal carcinoma.
Pathol Int. 2004 Oct ;54(10):781-6.

PubMed
Medulloblastoma in late adults. Case report and critical review of the literatur...
Medulloblastoma in late adults. Case report and critical review of the literature.
J Neurosurg Sci. 2000 Dec ;44(4):230-2; discussion 232-3.

PubMed
Investigation into the mechanism of phenolic couplings during the biosynthesis o...
Investigation into the mechanism of phenolic couplings during the biosynthesis of glycopeptide antibiotics.
Chembiochem. 2008 Sep 22 ;9(14):2209-14.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Display Settings:

Send to:

Synthesis, biochemical, and cellular evaluation of farnesyl monophosphate prodrugs as farnesyltransferase inhibitors.

Source

Abstract

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

LinkOut - more resources

Full Text Sources

Other Literature Sources

Supplemental Content

Related citations

Cited by 2 PubMed Central articles

Related information

Recent activity

Simple NCBI Directory

Getting Started

Resources

Popular

Featured

NCBI Information