ArticleBritish journal of pharmacology2003
Lipid-lowering properties of TAK-475, a squalene synthase inhibitor, in vivo and in vitro.
Article in British journal of pharmacology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 72 citations in OpenAlex.
- Targeting intracellular cholesterol imbalance rescues sarcomere-ER contact site signaling and ER remodeling in dilated cardiomyopathy.Signal transduction and targeted therapy · 2026Article
- Unraveling the Potential Pathogenic Role of Squalene Synthase (SQS) in Lung Cancer Using Enzyme Inhibitors as Molecular Tools.ACS medicinal chemistry letters · 2025Article
- Oral and Non-Oral Cholesterol-Lowering Drugs with PCSK9 and Other Biomolecules as Targets: Present Status and Future Prospects.Biomolecules · 2025Review
- Identification of non-conventional small molecule degraders and stabilizers of squalene synthase.Chemical science · 2023Article
- Review
- Large-Scale CRISPR Screen of LDLR Pathogenic Variants.Research (Washington, D.C.) · 2023Article
- Article
- Mevalonate Kinase Deficiency and Squalene Synthase Inhibitor (TAK-475): The Balance to Extinguish the Inflammation.Biomolecules · 2021Article
- Tetraspanin CD82 interaction with cholesterol promotes extracellular vesicle-mediated release of ezrin to inhibit tumour cell movement.Journal of extracellular vesicles · 2020Article
- A Component Formula of Chinese Medicine for Hypercholesterolemia Based on Virtual Screening and Biology Network.Evidence-based complementary and alternative medicine : eCAM · 2018Article
- Identification and prioritization of novel anti-Science advances · 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
- Differential Regulation of Gene Expression by Cholesterol Biosynthesis Inhibitors That Reduce (Pravastatin) or Enhance (Squalestatin 1) Nonsterol Isoprenoid Levels in Primary Cultured Mouse and Rat Hepatocytes.The Journal of pharmacology and experimental therapeutics · 2016Article
- Article
- Plasma cholesterol-lowering and transient liver dysfunction in mice lacking squalene synthase in the liver.Journal of lipid research · 2015Article
- Human isoprenoid synthase enzymes as therapeutic targets.Frontiers in chemistry · 2014Review
- Role of squalene synthase in prostate cancer risk and the biological aggressiveness of human prostate cancer.Prostate cancer and prostatic diseases · 2012Article
- LDL-C-lowering therapy: current and future therapeutic targets.Current cardiology reports · 2008Review
- Lapaquistat acetate, a squalene synthase inhibitor, changes macrophage/lipid-rich coronary plaques of hypercholesterolaemic rabbits into fibrous lesions.British journal of pharmacology · 2008Article
- A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence.Science (New York, N.Y.) · 2008Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. Squalene synthase is the enzyme that converts farnesyl pyrophosphate to squalene in the cholesterol biosynthesis pathway. We examined the lipid-lowering properties of 1-[[(3R,5S)-1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidine-4-acetic acid (TAK-475), a novel squalene synthase inhibitor. 2. TAK-475 inhibited hepatic cholesterol biosynthesis in rats (ED(50), 2.9 mg kg(-1)) and showed lipid-lowering effects in beagle dogs, marmosets, cynomolgus monkeys and Wistar fatty rats. 3. In marmosets, TAK-475 (30, 100 mg kg(-1), p.o., for 4 days) lowered both plasma non-high-density lipoprotein (HDL) cholesterol and triglyceride, but did not affect plasma HDL cholesterol. On the other hand, atorvastatin (10, 30 mg kg(-1), p.o., for 4 days) lowered the levels of all these lipids. A correlation between decrease in triglyceride and increase in HDL cholesterol was observed, and TAK-475 increased HDL cholesterol with a smaller decrease in triglyceride than did atorvastatin. 4. TAK-475 (60 mg kg(-1), p.o., for 15 days) suppressed the rate of triglyceride secretion from the liver in hypertriglyceridemic Wistar fatty rats, which show an enhanced triglyceride secretion rate from the liver compared with their lean littermates. 5. In HepG2 cells, TAK-475 and its pharmacologically active metabolite, T-91485, increased the binding of (125)I-low-density lipoprotein (LDL) to LDL receptors. 6. These results suggest that TAK-475 has clear hypolipidemic effects in animals via inhibition of hepatic triglyceride secretion and upregulation of LDL receptors, and that TAK-475 might increase HDL cholesterol by decreasing triglyceride. Thus, TAK-475 is expected to be useful for the treatment of dyslipidemia.
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