Literature DB >> 26713103

Potent Triazole Bisphosphonate Inhibitor of Geranylgeranyl Diphosphate Synthase.

Veronica S Wills1, Cheryl Allen2, Sarah A Holstein2, David F Wiemer3.   

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.

Entities:  

Keywords:  GGDPS; Geranylgeranyl diphosphate synthase; bisphosphonate; farnesyl diphosphate synthase; myeloma

Year:  2015        PMID： 26713103      PMCID： PMC4677368          DOI： 10.1021/acsmedchemlett.5b00334

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  14 in total

Review 1.  Geranylgeranyl diphosphate synthase: an emerging therapeutic target.

Authors:  A J Wiemer; D F Wiemer; R J Hohl
Journal:  Clin Pharmacol Ther       Date:  2011-11-02       Impact factor: 6.875

Review 2.  The relationship between the chemistry and biological activity of the bisphosphonates.

Authors:  Frank H Ebetino; Anne-Marie L Hogan; Shuting Sun; Maria K Tsoumpra; Xuchen Duan; James T Triffitt; Aaron A Kwaasi; James E Dunford; Bobby L Barnett; Udo Oppermann; Mark W Lundy; Alan Boyde; Boris A Kashemirov; Charles E McKenna; R Graham G Russell
Journal:  Bone       Date:  2011-04-09       Impact factor: 4.398

3.  Digeranyl bisphosphonate inhibits geranylgeranyl pyrophosphate synthase.

Authors:  Andrew J Wiemer; Huaxiang Tong; Kelly M Swanson; Raymond J Hohl
Journal:  Biochem Biophys Res Commun       Date:  2006-12-21       Impact factor: 3.575

Review 4.  Prodrugs of phosphonates and phosphates: crossing the membrane barrier.

Authors:  Andrew J Wiemer; David F Wiemer
Journal:  Top Curr Chem       Date:  2015

5.  Isoprenoid biosynthetic pathway inhibition disrupts monoclonal protein secretion and induces the unfolded protein response pathway in multiple myeloma cells.

Authors:  Sarah A Holstein; Raymond J Hohl
Journal:  Leuk Res       Date:  2010-09-09       Impact factor: 3.156

6.  Synthesis and biological activity of isoprenoid bisphosphonates.

Authors:  Larry W Shull; Andrew J Wiemer; Raymond J Hohl; David F Wiemer
Journal:  Bioorg Med Chem       Date:  2006-03-06       Impact factor: 3.641

7.  Geranyl and neryl triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase.

Authors:  Xiang Zhou; Sarah D Ferree; Veronica S Wills; Ella J Born; Huaxiang Tong; David F Wiemer; Sarah A Holstein
Journal:  Bioorg Med Chem       Date:  2014-03-24       Impact factor: 3.641

8.  Mono- and dialkyl isoprenoid bisphosphonates as geranylgeranyl diphosphate synthase inhibitors.

Authors:  Andrew J Wiemer; Jose S Yu; Kimberly M Lamb; Raymond J Hohl; David F Wiemer
Journal:  Bioorg Med Chem       Date:  2007-09-18       Impact factor: 3.641

9.  Pivaloyloxymethyl-modified isoprenoid bisphosphonates display enhanced inhibition of cellular geranylgeranylation.

Authors:  Andrew J Wiemer; Jose S Yu; Larry W Shull; Rocky J Barney; Brian M Wasko; Kimberly M Lamb; Raymond J Hohl; David F Wiemer
Journal:  Bioorg Med Chem       Date:  2008-02-08       Impact factor: 3.641

Review 10.  Human isoprenoid synthase enzymes as therapeutic targets.

Authors:  Jaeok Park; Alexios N Matralis; Albert M Berghuis; Youla S Tsantrizos
Journal:  Front Chem       Date:  2014-07-22       Impact factor: 5.221
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  20 in total

1.  In Vivo Evaluation of Isoprenoid Triazole Bisphosphonate Inhibitors of Geranylgeranyl Diphosphate Synthase: Impact of Olefin Stereochemistry on Toxicity and Biodistribution.

Authors:  Staci L Haney; Yashpal S Chhonker; Michelle L Varney; Geoffrey Talmon; Lynette M Smith; Daryl J Murry; Sarah A Holstein
Journal:  J Pharmacol Exp Ther       Date:  2019-08-16       Impact factor: 4.030

2.  ω-Hydroxy isoprenoid bisphosphonates as linkable GGDPS inhibitors.

Authors:  Nazmul H Bhuiyan; Michelle L Varney; Deep S Bhattacharya; William M Payne; Aaron M Mohs; Sarah A Holstein; David F Wiemer
Journal:  Bioorg Med Chem Lett       Date:  2019-08-20       Impact factor: 2.823

3.  Preclinical investigation of a potent geranylgeranyl diphosphate synthase inhibitor.

Authors:  Staci L Haney; Yashpal S Chhonker; Michelle L Varney; Geoffrey Talmon; Daryl J Murry; Sarah A Holstein
Journal:  Invest New Drugs       Date:  2018-03-02       Impact factor: 3.850

4.  Stereoselective Synthesis of Homoneryl and Homogeranyl Triazole Bisphosphonates.

Authors:  Robert A Matthiesen; Veronica S Wills; Joseph I Metzger; Sarah A Holstein; David F Wiemer
Journal:  J Org Chem       Date:  2016-09-20       Impact factor: 4.354

5.  Epidemiologic Analysis Along the Mevalonate Pathway Reveals Improved Cancer Survival in Patients Who Receive Statins Alone and in Combination With Bisphosphonates.

Authors:  Sherif M El-Refai; Joshua D Brown; Susanne M Arnold; Esther P Black; Markos Leggas; Jeffery C Talbert
Journal:  JCO Clin Cancer Inform       Date:  2017-11

Review 6.  Molecular mechanisms linking geranylgeranyl diphosphate synthase to cell survival and proliferation.

Authors:  Sherry S Agabiti; Yilan Liang; Andrew J Wiemer
Journal:  Mol Membr Biol       Date:  2016-08-18       Impact factor: 2.857

7.  Stereocontrolled regeneration of olefins from epoxides.

Authors:  Veronica S Wills; Xiang Zhou; Cheryl Allen; Sarah A Holstein; David F Wiemer
Journal:  Tetrahedron Lett       Date:  2016-03-23       Impact factor: 2.415

8.  Amides as bioisosteres of triazole-based geranylgeranyl diphosphate synthase inhibitors.

Authors:  Daniel B Goetz; Michelle L Varney; David F Wiemer; Sarah A Holstein
Journal:  Bioorg Med Chem       Date:  2020-06-30       Impact factor: 3.641

9.  A new motif for inhibitors of geranylgeranyl diphosphate synthase.

Authors:  Benjamin J Foust; Cheryl Allen; Sarah A Holstein; David F Wiemer
Journal:  Bioorg Med Chem       Date:  2016-06-10       Impact factor: 3.641

10.  Quantitative determination of a potent geranylgeranyl diphosphate synthase inhibitor using LC-MS/MS: Derivatization and application.

Authors:  Yashpal S Chhonker; Staci L Haney; Robert A Matthiesen; David F Wiemer; Sarah A Holstein; Daryl J Murry
Journal:  J Pharm Biomed Anal       Date:  2018-02-06       Impact factor: 3.935
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