Potent Triazole Bisphosphonate Inhibitor of Geranylgeranyl Diphosphate Synthase

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

doi:10.1021/acsmedchemlett.5b00334

Potent Triazole Bisphosphonate Inhibitor of Geranylgeranyl Diphosphate Synthase

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

Research output: Contribution to journal › Article › peer-review

32 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 language	English (US)
Pages (from-to)	1195-1198
Number of pages	4
Journal	ACS Medicinal Chemistry Letters
Volume	6
Issue number	12
DOIs	https://doi.org/10.1021/acsmedchemlett.5b00334
State	Published - Dec 10 2015
Externally published	Yes

Keywords

GGDPS
Geranylgeranyl diphosphate synthase
bisphosphonate
farnesyl diphosphate synthase
myeloma

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1021/acsmedchemlett.5b00334

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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.",

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AU - Wills, Veronica S.

AU - Allen, Cheryl

AU - Holstein, Sarah A.

AU - Wiemer, David F.

PY - 2015/12/10

Y1 - 2015/12/10

N2 - 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.

AB - 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.

KW - GGDPS

KW - Geranylgeranyl diphosphate synthase

KW - bisphosphonate

KW - farnesyl diphosphate synthase

KW - myeloma

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ER -

Potent Triazole Bisphosphonate Inhibitor of Geranylgeranyl Diphosphate Synthase

Abstract

Keywords

ASJC Scopus subject areas

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