title: Potent Triazole Bisphosphonate Inhibitor of Geranylgeranyl Diphosphate Synthase.
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.
authors.affiliation: Department of Chemistry, University of Iowa , Iowa City, Iowa 52242-1294, United States.
authors.forename: Veronica S
authors.initials: VS
authors.lastname: Wills
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute , Buffalo, New York 14263, United States.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Allen
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute , Buffalo, New York 14263, United States.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Holstein
authors.affiliation: Department of Chemistry, University of Iowa , Iowa City, Iowa 52242-1294, United States ; Department of Pharmacology, University of Iowa , Iowa City, Iowa 52242-1109, United States.
authors.forename: David F
authors.initials: DF
authors.lastname: Wiemer
keywords: GGDPS; Geranylgeranyl diphosphate synthase; bisphosphonate; farnesyl diphosphate synthase; myeloma