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Purity: ≥98%
| Targets |
Lapaquistat acetate targets squalene synthase, a key enzyme in the cholesterol biosynthesis pathway. By inhibiting this enzyme, it blocks the conversion of farnesyl diphosphate to squalene, a critical step in cholesterol synthesis. It acts downstream of HMG-CoA reductase, the target of statins.
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| ln Vitro |
Lapaquistat acetate is a squalene synthase inhibitor, blocking the conversion of farnesyl diphosphate to squalene in the cholesterol biosynthesis pathway. It has potential anti-inflammatory activity. It attenuates statin-induced cytotoxicity in human skeletal muscle cells and protects guinea pigs from cerivastatin-induced myotoxicity.
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| ln Vivo |
The dietary supplement laparestat acetate (100 or 200 mg/kg; 32 weeks) lowers triglyceride and cholesterol levels. It has the ability to both decrease and postpone the development of coronary atherosclerotic plaques in animals that are both unstable and numerous.
Lapaquistat acetate has been studied for its cholesterol-lowering effects in vivo. It attenuates statin-induced myotoxicity, suggesting it may have a role in combination therapy with statins. It has been studied for hypercholesterolemia and mevalonate kinase deficiency. It was abandoned before being marketed. |
| Enzyme Assay |
Lapaquistat acetate is evaluated in cell-free enzymatic assays using purified squalene synthase. The compound is incubated with the enzyme and its substrate, farnesyl diphosphate, and the inhibition of squalene synthesis is measured. IC50 values are determined to quantify the potency of inhibition.
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| Cell Assay |
Lapaquistat acetate is assessed in cell-based assays using hepatic cells to measure its effects on cholesterol biosynthesis. Cells are treated with Lapaquistat acetate, and cholesterol synthesis is measured by assessing the incorporation of labeled precursors. Its ability to attenuate statin-induced cytotoxicity is also studied.
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| Animal Protocol |
Animal/Disease Models: Male WHHLMI rabbit, 2 months old [3]
Doses: 100 or 200 mg/kg Route of Administration: Dietary supplement; macrophage-containing/gate-accumulating hazards are transformed into stable fiber hazards in the body [3]. 100 or 200 mg/kg; 32-week Experimental Results: Increased collagen concentration and conversion of coronary plaque to fibromuscular plaque. Inhibits the expression of MMP-1 and PAI-1 in plaques and increases peripheral coenzyme Q10 levels. Lapaquistat acetate is administered in animal models to evaluate its cholesterol-lowering effects and its ability to protect against statin-induced myotoxicity. It has been studied in models of hypercholesterolemia and mevalonate kinase deficiency. However, specific animal study protocols are not extensively documented. |
| ADME/Pharmacokinetics |
Lapaquistat acetate has a molecular weight of 645.14 and a molecular formula of C33H41ClN2O9. It has a CAS number of 189060-13-7. The compound is a squalene synthase inhibitor. It is almost insoluble in water.
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| Toxicity/Toxicokinetics |
No detailed toxicity data is available for Lapaquistat acetate beyond its preclinical profile. The compound is for research use only and is not intended for human therapeutic use. It was abandoned as a drug candidate before being marketed.
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| References |
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| Additional Infomation |
Tak-475 is an oxygen heterocyclic compound and an organic nitrogen heterocyclic compound. TAK-475 is a squalene synthase inhibitor, belonging to the category of cholesterol-lowering drugs not yet marketed. Lapaquistat Acetate is the acetate form of lapaquistat, a squalene synthase inhibitor, whose potential for treating hypercholesterolemia is currently being investigated. See also: Lapaquistat (note moved here). Drug Indications Its use for the treatment of hyperlipidemia is being investigated. Mechanism of Action Squalene synthase inhibitors are considered to have potential advantages over statins, which inhibit 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. HMG-CoA catalyzes its own conversion to mevalonate, and is therefore the main rate-limiting enzyme in hepatic cholesterol biosynthesis. Squalene synthase, located downstream of mevalonic acid, catalyzes the dimerization of farnesyl pyrophosphate to squalene. This is the only step in the cholesterol biosynthesis pathway responsible for cholesterol production. Researchers believe that blocking this site may prevent the effects of reduced isoprene intermediates and metabolites in the downstream pathway of HMG-CoA reductase.
Lapaquistat acetate is a squalene synthase inhibitor. It is also known as TAK-475. The compound has a CAS number of 189060-13-7. It was a cholesterol-lowering drug candidate that was abandoned. It is used in research to study cholesterol biosynthesis and lipid-lowering therapy. It is not approved for clinical use. |
| Molecular Formula |
C33H41CLN2O9
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| Molecular Weight |
645.14
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| Exact Mass |
644.25
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| CAS # |
189060-13-7
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| Related CAS # |
189060-13-7 (acetate);189059-71-0;
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| PubChem CID |
9874248
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| Appearance |
White to off-white solid powder
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| LogP |
4.874
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
45
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| Complexity |
1050
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC(=O)OCC(C)(C)CN1C2=C(C=C(C=C2)Cl)[C@H](O[C@@H](C1=O)CC(=O)N3CCC(CC3)CC(=O)O)C4=C(C(=CC=C4)OC)OC
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| InChi Key |
CMLUGNQVANVZHY-POURPWNDSA-N
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| InChi Code |
InChI=1S/C33H41ClN2O9/c1-20(37)44-19-33(2,3)18-36-25-10-9-22(34)16-24(25)30(23-7-6-8-26(42-4)31(23)43-5)45-27(32(36)41)17-28(38)35-13-11-21(12-14-35)15-29(39)40/h6-10,16,21,27,30H,11-15,17-19H2,1-5H3,(H,39,40)/t27-,30-/m1/s1
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| Chemical Name |
2-(1-(2-((3R,5S)-1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydrobenzo[e][1,4]oxazepin-3-yl)acetyl)piperidin-4-yl)acetic acid
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| Synonyms |
TAK 475 TAK-475 TAK475.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5501 mL | 7.7503 mL | 15.5005 mL | |
| 5 mM | 0.3100 mL | 1.5501 mL | 3.1001 mL | |
| 10 mM | 0.1550 mL | 0.7750 mL | 1.5501 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00532558 | Terminated | Drug: Lapaquistat acetate |
Hypercholesterolemia | Takeda | October 2007 | Phase 3 |
| NCT00865228 | Terminated | Drug: Lapaquistat acetate Drug: Placebo |
Hypercholesterolemia | Takeda | July 2007 | Phase 2 |
| NCT00263081 | Terminated | Drug: Lapaquistat acetate and current lipid-lowering treatmen |
Hypercholesterolemia | Takeda | November 2005 | Phase 3 |
| NCT00249899 | Terminated | Drug: Lapaquistat acetate and stable statin therapy |
Hypercholesterolemia | Takeda | November 2005 | Phase 3 |
| NCT00868127 | Completed | Drug: Lapaquistat acetate | Hypercholesterolemia | Takeda | December 2005 | Phase 3 |
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