Synonym
Lapaquistat acetate; TAK 475; TAK-475; TAK475.
IUPAC/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
InChi Key
CMLUGNQVANVZHY-POURPWNDSA-N
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
SMILES Code
O=C(O)CC1CCN(C(C[C@H]2O[C@H](C3=CC=CC(OC)=C3OC)C4=CC(Cl)=CC=C4N(CC(C)(C)COC(C)=O)C2=O)=O)CC1
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Preparing Stock Solutions
The following data is based on the
product
molecular weight
645.14
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
1: Ebihara T, Takeuchi T, Moriya Y, Tagawa Y, Kondo T, Moriwaki T, Asahi S. Characterization of Transporters in the Hepatic Uptake of TAK-475 M-I, a Squalene Synthase Inhibitor, in Rats and Humans. Drug Res (Stuttg). 2016 Jun;66(6):316-23. doi: 10.1055/s-0035-1569441. Epub 2016 Mar 24. PubMed PMID: 27011383.
2: Ebihara T, Teshima K, Kondo T, Tagawa Y, Moriwaki T, Asahi S. Pharmacokinetics of TAK-475, a Squalene Synthase Inhibitor, in Rats and Dogs. Drug Res (Stuttg). 2016 Jun;66(6):287-92. doi: 10.1055/s-0035-1569407. Epub 2016 Feb 2. PubMed PMID: 26839207.
3: Stein EA, Bays H, O'Brien D, Pedicano J, Piper E, Spezzi A. Lapaquistat acetate: development of a squalene synthase inhibitor for the treatment of hypercholesterolemia. Circulation. 2011 May 10;123(18):1974-85. doi: 10.1161/CIRCULATIONAHA.110.975284. Epub 2011 Apr 25. PubMed PMID: 21518985.
4: Liao JK. Squalene synthase inhibitor lapaquistat acetate: could anything be better than statins? Circulation. 2011 May 10;123(18):1925-8. doi: 10.1161/CIRCULATIONAHA.111.028571. Epub 2011 Apr 25. PubMed PMID: 21518979; PubMed Central PMCID: PMC3807098.
5: Kahlon AK, Roy S, Sharma A. Molecular docking studies to map the binding site of squalene synthase inhibitors on dehydrosqualene synthase of Staphylococcus aureus. J Biomol Struct Dyn. 2010 Oct;28(2):201-10. PubMed PMID: 20645653.
6: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Apr;30(3):231-51. PubMed PMID: 18597009.
7: Shiomi M, Yamada S, Amano Y, Nishimoto T, Ito T. Lapaquistat acetate, a squalene synthase inhibitor, changes macrophage/lipid-rich coronary plaques of hypercholesterolaemic rabbits into fibrous lesions. Br J Pharmacol. 2008 Jul;154(5):949-57. doi: 10.1038/bjp.2008.143. Epub 2008 Apr 21. PubMed PMID: 18587443; PubMed Central PMCID: PMC2451058.
8: Nishimoto T, Ishikawa E, Anayama H, Hamajyo H, Nagai H, Hirakata M, Tozawa R. Protective effects of a squalene synthase inhibitor, lapaquistat acetate (TAK-475), on statin-induced myotoxicity in guinea pigs. Toxicol Appl Pharmacol. 2007 Aug 15;223(1):39-45. Epub 2007 May 24. PubMed PMID: 17599378.
