ArticleJournal of medicinal chemistry2008
Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation.
Article in Journal of medicinal chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 82 citations in OpenAlex.
- Article
- α-Amino bisphosphonate triazoles serve as GGDPS inhibitors.Bioorganic & medicinal chemistry letters · 2024Article
- Structural Insight into Geranylgeranyl Diphosphate Synthase (GGDPS) for Cancer Therapy.Molecular cancer therapeutics · 2024Review
- Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target.Clinical and translational medicine · 2023Review
- Article
- Critical Insight into Plausible Acquired Tocopherol Pathway in Neglected Human Trypanosomatids.ACS omega · 2021Review
- Impact of α-modifications on the activity of triazole bisphosphonates as geranylgeranyl diphosphate synthase inhibitors.Bioorganic & medicinal chemistry · 2021Article
- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
- Structure, catalysis, and inhibition mechanism of prenyltransferase.IUBMB life · 2021Review
- Amides as bioisosteres of triazole-based geranylgeranyl diphosphate synthase inhibitors.Bioorganic & medicinal chemistry · 2020Article
- Targeting prenylation inhibition through the mevalonate pathway.RSC medicinal chemistry · 2020Review
- ω-Hydroxy isoprenoid bisphosphonates as linkable GGDPS inhibitors.Bioorganic & medicinal chemistry letters · 2019Article
- Discovery of Lipophilic Bisphosphonates That Target Bacterial Cell Wall and Quinone Biosynthesis.Journal of medicinal chemistry · 2019Article
- Structural characterization of geranylgeranyl pyrophosphate synthase GACE1337 from the hyperthermophilic archaeon Geoglobus acetivorans.Extremophiles : life under extreme conditions · 2018Article
- Bisphosphonate-Generated ATP-Analogs Inhibit Cell Signaling Pathways.Journal of the American Chemical Society · 2018Article
- Anti-Tumor Activity and Immunotherapeutic Potential of a Bisphosphonate Prodrug.Scientific reports · 2017Article
- Recent Advances in the Development of Mammalian Geranylgeranyl Diphosphate Synthase Inhibitors.Molecules (Basel, Switzerland) · 2017Review
- Olefin Isomers of a Triazole Bisphosphonate Synergistically Inhibit Geranylgeranyl Diphosphate Synthase.Molecular pharmacology · 2017Article
- Targeting Cancer Cells with a Bisphosphonate Prodrug.ChemMedChem · 2016Article
- Synthetic Procedures Leading towards Aminobisphosphonates.Molecules (Basel, Switzerland) · 2016Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
We report the X-ray structures of several bisphosphonate inhibitors of geranylgeranyl diphosphate synthase, a target for anticancer drugs. Bisphosphonates containing unbranched side chains bind to either the farnesyl diphosphate (FPP) substrate site, the geranylgeranyl diphosphate (GGPP) product site, and in one case, both sites, with the bisphosphonate moiety interacting with 3 Mg (2+) that occupy the same position as found in FPP synthase. However, each of three "V-shaped" bisphosphonates bind to both the FPP and GGPP sites. Using the Glide program, we reproduced the binding modes of 10 bisphosphonates with an rms error of 1.3 A. Activities of the bisphosphonates in GGPPS inhibition were predicted with an overall error of 2x by using a comparative molecular similarity analysis based on a docked-structure alignment. These results show that some GGPPS inhibitors can occupy both substrate and product site and that binding modes as well as activity can be accurately predicted, facilitating the further development of GGPPS inhibitors as anticancer agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.