Prenylation inhibitors in renal disease.

Abstract

Members of the superfamily of Ras GTPase signalling proteins (monomeric G proteins) require post-translational carboxy-terminal prenylation to function. Prenylation is the covalent attachment of a hydrophobic prenyl group (either farnesyl or geranylgeranyl), which localises the GTPase to cell membranes. Ras proteins exert substantial control on cell proliferation and gene-transcription events, and prenylation inhibitors are now included in clinical trials for cancer. Many renal diseases are highly proliferative and are driven by a range of profibrotic cytokines. We hypothesise that inhibition of prenylation could be of substantial therapeutic benefit in such diseases, providing greater selectivity against abnormal cytokine-driven proliferation and fibrogenesis than current treatments available to nephrologists.

• Authors: A Khwaja, J O'Connolly, B M Hendry
• Journal: Lancet (London, England) (Lancet) Vol. 355 Issue 9205 Pg. 741-4 (Feb 26 2000) ISSN: 0140-6736 [Print] England
• PMID: 10703816 (Publication Type: Journal Article, Review)

Chemical References

• GTP Phosphohydrolases
• ras Proteins

Topics

• Animals
• Cell Division (drug effects)
• GTP Phosphohydrolases (metabolism)
• Humans
• Kidney Diseases (drug therapy)
• Protein Prenylation (drug effects)
• ras Proteins (therapeutic use)