Potent Triazole Bisphosphonate Inhibitor of Geranylgeranyl Diphosphate Synthase

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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Geranyltranstransferase
Farnesyltranstransferase
Lead compounds
Triazoles
Diphosphonates
Cytotoxicity
Inhibitory Concentration 50
Prenylation
Enzymes
Proteins
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

Cite this

Potent Triazole Bisphosphonate Inhibitor of Geranylgeranyl Diphosphate Synthase. / Wills, Veronica S.; Allen, Cheryl; Holstein, Sarah A; Wiemer, David F.

In: ACS Medicinal Chemistry Letters, Vol. 6, No. 12, 10.12.2015, p. 1195-1198.

Research output: Contribution to journalArticle

Wills, Veronica S. ; Allen, Cheryl ; Holstein, Sarah A ; Wiemer, David F. / Potent Triazole Bisphosphonate Inhibitor of Geranylgeranyl Diphosphate Synthase. In: ACS Medicinal Chemistry Letters. 2015 ; Vol. 6, No. 12. pp. 1195-1198.
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