Lapaquistat | CAS#189059-71-0 | squalene synthase inhibitor

MedKoo Cat#: 559061 | Name: Lapaquistat

Description:

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

Lapaquistat, also known as T 91485, is a squalene synthase inhibitor. T-91485, an active metabolite of the squalene synthase inhibitor lapaquistat acetate (TAK-475), attenuated statin-induced cytotoxicity in human skeletal muscle cells. T-91485 potently inhibited cholesterol synthesis in RD cells, the IC(25) value exceeded 100 microM. In human skeletal myocytes, T-91485 concentration-dependently inhibited cholesterol biosynthesis, with IC(50) values of 45 nM,.

Chemical Structure

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: 603.10

Elemental Analysis: C, 61.74; H, 6.52; Cl, 5.88; N, 4.64; O, 21.22

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.

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Related CAS #

189060-13-7 (acetate) 189059-71-0

Synonym

Lapaquistat; T 91485; T-91485; T91485;

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

More Info

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 603.10 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: 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.