Farnesyl pyrophosphate synthase modulators: a patent review (2006 - 2010)

Expert Opin Ther Pat. 2011 Sep;21(9):1433-51. doi: 10.1517/13543776.2011.593511. Epub 2011 Jun 25.


Introduction: Farnesyl pyrophosphate synthase (FPPS, also known as farnesyl diphosphate synthase (FDPS)) is one of the key enzymes involved in the mevalonate pathway and as such is widely expressed. FPPS modulators, specifically FPPS inhibitors, are useful in treating a number of diseases, including bone-related disorders characterized by excessive bone resorption, for example, osteoporosis, cancer metathesis to bone and infectious diseases caused by certain parasites.

Areas covered: This review covers structures and applications of novel FPPS modulators described in the patent literature from 2006 to 2010. Patents disclosing new formulations and uses of existing FPPS inhibitors are also reviewed. Thirty-three patents retrieved from the USPTO, EP and WIPO databases are examined with the goal of defining current trends in drug discovery related to FPPS inhibition, and its therapeutic effects.

Expert opinion: Bisphosphonates (BPs) continue to dominate in this area, although other types of modulators are making their appearance. Remarkable for their high bone mineral affinity, BPs are structural mimics of the dimethylallyl pyrophosphate substrate of FPPS, and constitute the major type of FPPS inhibitor currently used in the clinic for treatment of bone-related diseases. Lipophilic BPs and new classes of non-BP FPPS inhibitors (salicylic acid and quinoline derivatives) have been introduced as possible alternatives for treatment of soft tissue diseases, such as some cancers. Novel formulations, fluorescent diagnostic probes and new therapeutic applications of existing FPPS inhibitors are also areas of significant patent activity, demonstrating growing recognition of the versatility and underdeveloped potential of these drugs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Resorption / drug therapy
  • Chemistry, Pharmaceutical
  • Diphosphonates / chemical synthesis
  • Diphosphonates / chemistry
  • Diphosphonates / pharmacology
  • Geranyltranstransferase / antagonists & inhibitors*
  • Geranyltranstransferase / metabolism*
  • Humans
  • Mevalonic Acid / metabolism
  • Organophosphonates / pharmacology
  • Patents as Topic
  • Quinolines / chemical synthesis
  • Quinolines / pharmacology
  • Salicylates / chemical synthesis
  • Salicylates / pharmacology


  • Diphosphonates
  • Organophosphonates
  • Quinolines
  • Salicylates
  • Geranyltranstransferase
  • Mevalonic Acid