ArticleJournal of lipid research2011
A novel bisphosphonate inhibitor of squalene synthase combined with a statin or a nitrogenous bisphosphonate in vitro.
Article in Journal of lipid research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 34 citations in OpenAlex.
- Review
- Does Ras/Rho Have Skin in the Game: The Importance of the Isoprenoid Biosynthesis Pathway in Merkel Cell Carcinoma Cell Lines.Cancers · 2026Article
- Research progress and therapeutic strategies in hepatocellular carcinoma metabolic reprogramming.Journal of advanced research · 2026Review
- Exploring Metabolic Approaches for Epithelial Ovarian Cancer Therapy.Journal of cellular physiology · 2025Review
- Identification of non-conventional small molecule degraders and stabilizers of squalene synthase.Chemical science · 2023Article
- Integrated transcriptomic and proteomic analyses reveal the mechanism of easy acceptance of artificial pelleted diets during food habit domestication in Largemouth bass (Micropterus salmoides).Scientific reports · 2023Article
- Review
- Bisphosphonate inhibitors of squalene synthase protect cells against cholesterol-dependent cytolysins.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Dietary Trivalent Chromium Exposure Up-Regulates Lipid Metabolism in Coral Trout: The Evidence From Transcriptome Analysis.Frontiers in physiology · 2021Article
- Epidemiologic Analysis Along the Mevalonate Pathway Reveals Improved Cancer Survival in Patients Who Receive Statins Alone and in Combination With Bisphosphonates.JCO clinical cancer informatics · 2017Article
- A Genomic DNA Reporter Screen Identifies Squalene Synthase Inhibitors That Act Cooperatively with Statins to Upregulate the Low-Density Lipoprotein Receptor.The Journal of pharmacology and experimental therapeutics · 2017Article
- Plasma cholesterol-lowering and transient liver dysfunction in mice lacking squalene synthase in the liver.Journal of lipid research · 2015Article
- Unbiased analysis of pancreatic cancer radiation resistance reveals cholesterol biosynthesis as a novel target for radiosensitisation.British journal of cancer · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Statins and nitrogenous bisphosphonates (NBP) inhibit 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR) and farnesyl diphosphate synthase (FDPS), respectively, leading to depletion of farnesyl diphosphate (FPP) and disruption of protein prenylation. Squalene synthase (SQS) utilizes FPP in the first committed step from the mevalonate pathway toward cholesterol biosynthesis. Herein, we have identified novel bisphosphonates as potent and specific inhibitors of SQS, including the tetrasodium salt of 9-biphenyl-4,8-dimethyl-nona-3,7-dienyl-1,1-bisphosphonic acid (compound 5). Compound 5 reduced cholesterol biosynthesis and lead to a substantial intracellular accumulation of FPP without reducing cell viability in HepG2 cells. At high concentrations, lovastatin and zoledronate impaired protein prenylation and decreased cell viability, which limits their potential use for cholesterol depletion. When combined with lovastatin, compound 5 prevented lovastatin-induced FPP depletion and impairment of protein farnesylation. Compound 5 in combination with the NBP zoledronate completely prevented zoledronate-induced impairment of both protein farnesylation and geranylgeranylation. Cotreatment of cells with compound 5 and either lovastatin or zoledronate was able to significantly prevent the reduction of cell viability caused by lovastatin or zoledronate alone. The combination of an SQS inhibitor with an HMGCR or FDPS inhibitor provides a rational approach for reducing cholesterol synthesis while preventing nonsterol isoprenoid depletion.
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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.