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Purity: ≥98%
Lapaquistat acetate, formerly known as TAK475, is a novel and potent squalene synthase inhibitor used as a cholesterol-lowering drug. As a squalene synthase inhibitor, Lapaquistat block the conversion of farnesyl diphosphate (FPP) to squalene. Lapaquistat acetate was originally designed for treating Mevalonate Kinase Deficiency (MKD), it is effective at lowering low-density lipoprotein cholesterol, but it might cause liver damage.
| 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.
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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. |
| References |
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| Additional Infomation |
Tak-475 is an oxacycle and an organonitrogen heterocyclic compound.
TAK-475 is a "squalene synthase inhibitor", a type of cholesterol-lowering drug that has not yet been brought to market. Lapaquistat Acetate is an acetate salt form of lapaquistat, a squalene synthase inhibitor investigated for the treatment of hypercholesterolemia. See also: Lapaquistat (annotation moved to). Drug Indication Investigated for use/treatment in hyperlipidemia. Mechanism of Action Squalene synthase inhibitors are believed to have potential advantages over statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. HMG-CoA catalyzes the conversion of HMG-CoA to mevalonate and thus serves as the primary rate-limiting enzyme in the hepatic biosynthesis of cholesterol. Squalene synthase acts downstream of mevalonate, catalyzing the dimerization of farnesyl-pyrophosphate to squalene. This is the first step in the cholesterol biosynthetic pathway that is solely committed to the production of cholesterol, and researchers believe that blockade at this site may avoid the effects associated with decreased formation of isoprenolated intermediates and metabolites in the pathway beyond HMG-CoA reductase. |
| 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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