Potent Triazole Bisphosphonate Inhibitor of Geranylgeranyl Diphosphate Synthase

Veronica S. Wills, Cheryl Allen, Sarah A. Holstein, David F. Wiemer

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Studies of triazole bisphosphonates have resulted in identification of a potent inhibitor of geranylgeranyl diphosphate synthase (IC50 = 45 nM) with very good selectivity for this enzyme over farnesyl diphosphate synthase (IC50 = 28 μM). This compound also potently disrupts geranylgeranylation and induces cytotoxicity in human myeloma cells at submicromolar levels, suggesting that it may serve as a lead compound for treatment of malignancies characterized by excessive protein secretion.

Original languageEnglish (US)
Pages (from-to)1195-1198
Number of pages4
JournalACS Medicinal Chemistry Letters
Volume6
Issue number12
DOIs
StatePublished - Dec 10 2015

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Keywords

  • GGDPS
  • Geranylgeranyl diphosphate synthase
  • bisphosphonate
  • farnesyl diphosphate synthase
  • myeloma

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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