Lapaquistat

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 559061

CAS#: 189059-71-0

Description: Lapaquistat is a squalene synthase inhibitor.


Chemical Structure

img
Lapaquistat
CAS# 189059-71-0

Theoretical Analysis

MedKoo Cat#: 559061
Name: Lapaquistat
CAS#: 189059-71-0
Chemical Formula: C31H39ClN2O8
Exact Mass: 602.2395
Molecular Weight: 603.1
Elemental Analysis: C, 61.74; H, 6.52; Cl, 5.88; N, 4.64; O, 21.22

Price and Availability

This product is not in stock, which may be available by custom synthesis. For cost-effective reason, minimum order is 1g (price is usually high, lead time is 2~3 months, depending on the technical challenge). Quote less than 1g will not be provided. To request quote, please email to sales @medkoo.com or click below button.
Note: Price will be listed if it is available in the future.

Request quote for custom synthesis

Related CAS #: 189060-13-7 (acetate)  

Synonym: Lapaquistat;

IUPAC/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

InChi Key: HDGUKVZPMPJBFK-LEAFIULHSA-N

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

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)CO)C2=O)=O)CC1

Appearance: Solid powder

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: >3 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 603.1 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.

Recalculate based on batch purity %
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

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: 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.

2: 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.

3: Elsayed RK, Evans JD. Emerging lipid-lowering drugs: squalene synthase inhibitors. Expert Opin Emerg Drugs. 2008 Jun;13(2):309-22. doi: 10.1517/14728214.13.2.309 . Review. PubMed PMID: 18537523.

4: 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.

5: 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.

6: 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.

7: 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.

8: 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.

9: Seiki S, Frishman WH. Pharmacologic inhibition of squalene synthase and other downstream enzymes of the cholesterol synthesis pathway: a new therapeutic approach to treatment of hypercholesterolemia. Cardiol Rev. 2009 Mar-Apr;17(2):70-6. doi: 10.1097/CRD.0b013e3181885905. Review. PubMed PMID: 19367148.

10: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Apr;30(3):231-51. PubMed PMID: 18597009.

11: Suzuki N, Ito T, Matsui H, Takizawa M. Anti-inflammatory and cytoprotective effects of a squalene synthase inhibitor, TAK-475 active metabolite-I, in immune cells simulating mevalonate kinase deficiency (MKD)-like condition. Springerplus. 2016 Aug 30;5(1):1429. doi: 10.1186/s40064-016-3125-1. eCollection 2016. PubMed PMID: 27652005; PubMed Central PMCID: PMC5005254.

12: Bayes M. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2007 Mar;29(2):153-73. PubMed PMID: 17440629.

13: Davidson MH. Novel nonstatin strategies to lower low-density lipoprotein cholesterol. Curr Atheroscler Rep. 2009 Jan;11(1):67-70. Review. PubMed PMID: 19080731.

14: Burnett JR. Drug evaluation: TAK-475--an oral inhibitor of squalene synthase for hyperlipidemia. Curr Opin Investig Drugs. 2006 Sep;7(9):850-6. Review. PubMed PMID: 17002264.

15: Davidson MH. Squalene synthase inhibition: a novel target for the management of dyslipidemia. Curr Atheroscler Rep. 2007 Jan;9(1):78-80. PubMed PMID: 17169251.

16: Marcuzzi A, Loganes C, Celeghini C, Kleiner G. Repositioning of Tak-475 In Mevalonate Kinase Disease: Translating Theory Into Practice. Curr Med Chem. 2018;25(24):2783-2796. doi: 10.2174/0929867324666170911161417. Review. PubMed PMID: 28901277.

17: Miki T, Kori M, Mabuchi H, Tozawa R, Nishimoto T, Sugiyama Y, Teshima K, Yukimasa H. Synthesis of novel 4,1-benzoxazepine derivatives as squalene synthase inhibitors and their inhibition of cholesterol synthesis. J Med Chem. 2002 Sep 26;45(20):4571-80. PubMed PMID: 12238936.

18: Nishimoto T, Amano Y, Tozawa R, Ishikawa E, Imura Y, Yukimasa H, Sugiyama Y. Lipid-lowering properties of TAK-475, a squalene synthase inhibitor, in vivo and in vitro. Br J Pharmacol. 2003 Jul;139(5):911-8. PubMed PMID: 12839864; PubMed Central PMCID: PMC1573926.

19: Amano Y, Nishimoto T, Tozawa Ri, Ishikawa E, Imura Y, Sugiyama Y. Lipid-lowering effects of TAK-475, a squalene synthase inhibitor, in animal models of familial hypercholesterolemia. Eur J Pharmacol. 2003 Apr 11;466(1-2):155-61. PubMed PMID: 12679152.

20: Nishimoto T, Tozawa R, Amano Y, Wada T, Imura Y, Sugiyama Y. Comparing myotoxic effects of squalene synthase inhibitor, T-91485, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in human myocytes. Biochem Pharmacol. 2003 Dec 1;66(11):2133-9. PubMed PMID: 14609738.