| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
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Purity: ≥98%
Lapaquistat (T-91485), the active metabolite of TAK-475, 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 Vitro |
In differentiated RD (rhabdomyosarcoma) cells, lapaquistat inhibits cholesterol biosynthesis with an IC50 of 36 nM [1]. RD cells are efficiently inhibited from synthesizing cholesterol by lapaquistat, with an IC25 greater than 100 μM [1]. In human skeletal muscle cells, lapaquistat inhibits cholesterol biosynthesis in a concentration-dependent manner with an IC50 of 45 nM [1].
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| ln Vivo |
Lapostat acetate is quickly absorbed and converted into the pharmacologically active metabolite lapostat by rats after oral treatment [1].
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| References | |
| Additional Infomation |
Lapaquistat is under investigation in clinical trial NCT00256178 (Efficacy of Lapaquistat Acetate and Simvastatin in Subjects With Primary Dyslipidemia.).
Lapaquistat is an inhibitor of squalene synthase, an enzyme downstream of HMG-CoA reductase in the synthesis of cholesterol. Squalene synthase catalyzes the dimerization of farnesyl-pyrophosphate to squalene, the first step in the cholesterol biosynthetic pathway that is solely committed to the production of cholesterol. Development of this agent was haulted do to potential hepatic toxicity. |
| Molecular Formula |
C31H39CLN2O8
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|---|---|
| Molecular Weight |
603.1
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| Exact Mass |
602.239
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| CAS # |
189059-71-0
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| Related CAS # |
189060-13-7 (acetate);189059-71-0;
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| PubChem CID |
9960389
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| Appearance |
White to off-white solid powder
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| Density |
1.261g/cm3
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| Boiling Point |
824.024ºC at 760 mmHg
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| Flash Point |
452.154ºC
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| Vapour Pressure |
0mmHg at 25°C
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| Index of Refraction |
1.565
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| LogP |
4.303
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
42
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| Complexity |
942
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC(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)CO
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| InChi Key |
HDGUKVZPMPJBFK-LEAFIULHSA-N
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| InChi Code |
InChI=1S/C31H39ClN2O8/c1-31(2,18-35)17-34-23-9-8-20(32)15-22(23)28(21-6-5-7-24(40-3)29(21)41-4)42-25(30(34)39)16-26(36)33-12-10-19(11-13-33)14-27(37)38/h5-9,15,19,25,28,35H,10-14,16-18H2,1-4H3,(H,37,38)/t25-,28-/m1/s1
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| Chemical Name |
2-(1-(2-((3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-1,2,3,5-tetrahydrobenzo[e][1,4]oxazepin-3-yl)acetyl)piperidin-4-yl)acetic acid
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| Synonyms |
T-91485T91485T 91485TAK 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) |
DMSO : ~25 mg/mL (~41.45 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.83 mg/mL (1.38 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.83 mg/mL (1.38 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 0.83 mg/mL (1.38 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6581 mL | 8.2905 mL | 16.5810 mL | |
| 5 mM | 0.3316 mL | 1.6581 mL | 3.3162 mL | |
| 10 mM | 0.1658 mL | 0.8290 mL | 1.6581 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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