Geranylgeranyl diphosphate synthase: an emerging therapeutic target

Clin Pharmacol Ther. 2011 Dec;90(6):804-12. doi: 10.1038/clpt.2011.215. Epub 2011 Nov 2.


Proteins modified post-translationally by geranylgeranylation have been implicated in numerous cellular processes related to human disease. In recent years, the study of protein geranylgeranylation has advanced tremendously in both cellular and animal models. The advances in our understanding of the biological roles of geranylgeranylated proteins have been paralleled by advances in the medicinal chemistry of geranylgeranylation inhibitors such as those that target geranylgeranyl transferases I and II and geranylgeranyl diphosphate synthase (GGDPS). Although these findings provide the rationale for further development of geranylgeranylation as a therapeutic target, more advanced studies on the efficacy of this approach in various disease models will be required to support translation to clinical studies. This article attempts to describe the advances in (and the challenges of) validation of GGDPS as a novel therapeutic target and assesses the advantages of targeting GGDPS relative to other enzymes involved in geranylgeranylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Animals
  • Disease Models, Animal
  • Drug Delivery Systems*
  • Drug Design
  • Enzyme Inhibitors / pharmacology
  • Farnesyltranstransferase / antagonists & inhibitors*
  • Humans
  • Protein Prenylation / drug effects
  • Protein Processing, Post-Translational
  • Transferases / antagonists & inhibitors*


  • Enzyme Inhibitors
  • Rab geranylgeranyl transferase beta-subunit
  • Transferases
  • Alkyl and Aryl Transferases
  • geranylgeranyltransferase type-I
  • Farnesyltranstransferase