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Potent Triazole Bisphosphonate Inhibitor of Geranylgeranyl Diphosphate Synthase
Journal article   Open access   Peer reviewed

Potent Triazole Bisphosphonate Inhibitor of Geranylgeranyl Diphosphate Synthase

Veronica S Wills, Cheryl Allen, Sarah A Holstein and David F Wiemer
ACS Medicinal Chemistry Letters, Vol.6(12), pp.1195-1198
2015
DOI: 10.1021/acsmedchemlett.5b00334
PMCID: PMC4677368
PMID: 26713103
url
https://doi.org/10.1021/acsmedchemlett.5b00334View
Published (Version of record) Open Access

Abstract

Studies of triazole bisphosphonates have resulted in identification of a potent inhibitor of geranylgeranyl diphosphate synthase (IC 50 = 45 nM) with very good selectivity for this enzyme over farnesyl diphosphate synthase (IC 50 = 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.
Letter bisphosphonate myeloma Geranylgeranyl diphosphate synthase farnesyl diphosphate synthase GGDPS

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