Lapaquistat acetate  (Synonyms: TAK-475)

Lapaquistat acetate (TAK-475) is a squalene synthase inhibitor, blocking the conversion of farnesyl diphosphate (FPP) to squalene in the cholesterol biosynthesis pathway^[1]. Lapaquistat acetate is effective at lowering low-density lipoprotein cholesterol, but it might cause liver damage. Lapaquistat acetate is used for hypercholesterolemia and mevalonate kinase deficiency (MKD) research^[2].

Squalene synthase^[1]

Lapaquistat acetate (diet supplemented; 100 or 200?mg/kg; 32 weeks) decreases plasma cholesterol and triglyceride levels. It?delays progression of coronary atherosclerosis and changes coronary atheromatous plaques from unstable, macrophage/lipid accumulation-rich, lesions to stable fibromuscular lesions in vivo^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

645.14

C₃₃H₄₁ClN₂O₉

189060-13-7

Solid

White to off-white

O=C(O)CC1CCN(C(C[C@@H]2C(N(CC(C)(C)COC(C)=O)C3=CC=C(Cl)C=C3[C@@H](C4=CC=CC(OC)=C4OC)O2)=O)=O)CC1

Room temperature in continental US; may vary elsewhere.

• [1]. Stein EA, et al. Lapaquistat acetate: development of a squalene synthase inhibitor for the treatment of hypercholesterolemia. Circulation. 2011 May 10;123(18):1974-85.  [Content Brief]

  [2]. Marcuzzi A, et al. Repositioning of Tak-475 In Mevalonate Kinase Disease: Translating Theory Into Practice. Curr Med Chem. 2018;25(24):2783-2796.  [Content Brief]

  [3]. M Shiomi, et al. 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.  [Content Brief]