Potential role of nonstatin cholesterol lowering agents

IUBMB Life

Volumn 63, Issue 11, 2011, Pages 964-971

  Trapani, Laura ^a   Segatto, Marco ^a   Ascenzi, Paolo ^a   Pallottini, Valentina ^a  

^a ROMA TRE UNIVERSITY   (Italy)

Author keywords

3 hydroxy 3 methylglutaryl coenzyme a reductase; Cholesterol; Hypercholesterolemia; Inhibition; Oxidosqualene cyclase; Squalene epoxidase; Squalene synthase

Indexed keywords

1 PIPERIDINECARBOXYLIC ACID 4 DIMETHYLAMINO 2 ISOPROPYL 5 METHYLPHENYL ESTER; 3 [(3,3' BITHIOPHEN 5 YL)METHOXY] N (6,6 DIMETHYL 2 HEPTEN 4 YNYL) N ETHYLBENZYLAMINE; 3BETA (2 DIETHYLAMINOETHOXY)ANDROST 5 EN 17 ONE; ALLIIN; ANTILIPEMIC AGENT; BMS 187745; BMS 188494; CHOLESTEROL; DIALLYL TRISULFIDE; DOLICHOL; EP 2306; FR 194738; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ISOPRENOID; LANOSTEROL; LANOSTEROL SYNTHASE; LANOSTEROL SYNTHASE INHIBITOR; LAPAQUISTAT; MORPHOLINE DERIVATIVE; NATURAL PRODUCT; RO 48 8071; SQUALENE EPOXIDASE INHIBITOR; SQUALENE MONOOXYGENASE; SQUALENE SYNTHASE; SQUALENE SYNTHASE INHIBITOR; UBIQUINONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZARAGOZIC ACID A; ZARAGOZIC ACID C;

ABETALIPOPROTEINEMIA; ANTIFUNGAL ACTIVITY; ANTIOXIDANT ACTIVITY; ATHEROGENESIS; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; BACKACHE; BIOSYNTHESIS; CARDIOVASCULAR DISEASE; CATARACT; CATARACTOGENESIS; CHOLESTEROL METABOLISM; DISEASE COURSE; DOSE RESPONSE; DRUG EFFECT; DRUG MEGADOSE; DRUG SAFETY; DRUG TARGETING; DRUG WITHDRAWAL; ENZYME ACTIVITY; ENZYME INHIBITION; GARLIC; HEADACHE; HUMAN; HYPERCHOLESTEROLEMIA; LIVER TOXICITY; LOW DRUG DOSE; MACROPHAGE; MYALGIA; MYOGLOBINURIA; NEPHROTOXICITY; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RETINOPATHY; REVIEW; RHABDOMYOLYSIS; SIGNAL TRANSDUCTION; SKIN TOXICITY; TEA; TREATMENT OUTCOME;

ANIMALS; ANTICHOLESTEREMIC AGENTS; CHOLESTEROL; CLINICAL TRIALS AS TOPIC; FARNESYL-DIPHOSPHATE FARNESYLTRANSFERASE; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERCHOLESTEROLEMIA; INTRAMOLECULAR TRANSFERASES; MOLECULAR TARGETED THERAPY; SQUALENE MONOOXYGENASE;

EID: 84055199986     PISSN: 15216543     EISSN: 15216551     Source Type: Journal    
DOI: 10.1002/iub.522     Document Type: Review

References (58)

1. Yilmaz, M. B., Pinar, M., Naharci, I., Demirkan, B., Baysan, O., et al. (2005) Being well-informed about statin is associated with continuous adherence and reaching targets. Cardiovasc. Drugs Ther. 19, 437-440. (Pubitemid 43228156)
2. Trapani, L. and Pallottini, V. (2010). Age-related hypercholesterolemia and HMG-CoA reductase dysregulation: sex does matter (a gender perspective). Curr. Gerontol. Geriatr. Res. 420139.
3. Ogura, T., Tanaka, Y., Nakata, T., Namikawa, T., Kataoka, H., and Ohtsubo, Y. (2007). Simvastatin reduces insulin-like growth factor-1 signaling in differentiating C2C12 mouse myoblast cells in an HMG-CoA reductase inhibition-independent manner. J. Toxicol. Sci. 32, 57-67. (Pubitemid 46334070)
4. Golomb, B. A., Kopersk, S., and Evans, M. A. (2010). Statins and muscle adverse effects: a complementary perspective. Drug Saf. 33, 803; author reply 803-804.
5. Dirks, A. J. and Jones, K. M. (2006). Statin-induced apoptosis and skeletal myopathy. Am. J. Physiol. Cell. Physiol. 291, C1208-C1212. (Pubitemid 44878591)
6. Armitage, J. (2007). The safety of statins in clinical practice. Lancet 370, 1781-1790. (Pubitemid 350137473)
7. Osorio, F. G., Obaya, A. J., Lopez-Otin, C., and Freije, J. M. (2009). Accelerated ageing: from mechanism to therapy through animal models. Transgenic Res. 18, 7-15.
8. Eckert, G. P., Hooffm G. P., Strandjordm, M., Igbavboa, U., Volmer, D. A., et al. (2009). Regulation of the brain isoprenoids farnesyl-and geranylgeranylpyrophosphate is altered in male Alzheimer patients. Neurobiol. Dis. 35, 251-257.
9. Corbeel, L. and Freson, K. (2008). Rab proteins and Rab-associated proteins: major actors in the mechanism of protein-trafficking disorders. Eur. J. Pediatr. 167, 723-729.
10. Maeda, A., Yano, T., Itoh, Y., Kakumori, M., Kubota, T., et al. (2009). Down-regulation of RhoA is involved in the cytotoxic action of lipophilic statins in HepG2 cells. Atherosclerosis 208, 112-118.
11. Martini, C. and Pallottini, V. (2007). Cholesterol: from feeding to gene regulation. Genes Nutr. 2, 181-193.
12. Rezen, T. (2010). The impact of cholesterol and its metabolites on drug metabolism. Expert. Opin. Drug Metab. Toxicol. 1814, 146-160.
13. Bays, H. E., Neff, D., Tomassini, J. E., and Tershakovec, A. M. (2008). Ezetimibe: cholesterol lowering and beyond. Expert. Rev. Cardiovasc. Ther. 6, 447-470.
14. Segatto, M., Trapani, L., Marino, and M., Pallottini, V. (2011). Ageand sex-related differences in extrahepatic low density lipoprotein receptor. J. Cell. Physiol., in press.
15. Espenshade, P. J. and Hughes, A. L. (2007). Regulation of sterol synthesis in eukaryotes. Annu. Rev. Genet. 41, 401-427.
16. Rozman, D. and Monostory, K. (2010). Perspectives of the non-statin hypolipidemic agents. Pharmacol. Ther. 127, 19-40.
17. Istvan, E. S. and Deisenhofer, J. (2001). Structural mechanism for statin inhibition of HMG-CoA reductase. Science 292, 1160-1164. (Pubitemid 32440937)
18. Chasman, D. I., Posada, D., Subrahmanyan, L., Cook, N. R., Stanton, V. P. Jr., and Ridker, P. M. (2004). Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA 291, 2821-2827. (Pubitemid 38747801)
19. Trapani, L., Violo, F., and Pallottini, V. (2010). Hypercholesterolemia and 3-hydroxy-3-methylglutaryl coenzyme A reductase regulation in aged female rats. Exp. Gerontol. 45, 119-128.
20. Cham, S., Evans, M. A., Denenberg, J. O., and Golomb, B. A. (2010). Statin-associated muscle-related adverse effects: a case series of 354 patients. Pharmacotherapy 30, 541-553.
21. Brown, G. R., Hollinshead, D. M., Stokes, E. S., Clarke, D. S., Eakin, M. A., et al. (1999). Quinuclidine inhibitors of 2, 3-oxidosqualene cyclase-lanosterol synthase: optimization from lipid profiles. J. Med. Chem. 42, 1306-1311. (Pubitemid 29181152)
22. Pandit, J., Danleym, D. E., Schulte, G. K., Mazzalupo, S., Pauly, T. A., et al. (2000). Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis. J. Biol. Chem. 275, 30610-30617.
23. Tansey, T. R. and Shechter, I. (2000). Structure and regulation of mammalian squalene synthase. Biochim. Biophys. Acta. 1529, 49-62.
24. Charlton-Menys, V. and Durrington, P. N. (2007). Squalene synthase inhibitors: clinical pharmacology and cholesterol-lowering potential. Drugs 67, 11-16. (Pubitemid 46105084)
25. Ugawa, T., Kakuta, H., Moritani, H., and Inagaki, O. (2002). Effect of YM-53601, a novel squalene synthase inhibitor, on the clearance rate of plasma LDL and VLDL in hamsters. Br. J. Pharmacol. 137, 561-569.
26. Elsayed, R. K. and Evans, J. D. (2008). Emerging lipid-lowering drugs: squalene synthase inhibitors. Expert Opin. Emerg. Drugs 13, 309-322. (Pubitemid 351957350)
27. Burnett, J. R. (2006). Drug evaluation: TAK-475-an oral inhibitor of squalene synthase for hyperlipidemia. Curr. Opin. Investig. Drugs 7, 850-856. (Pubitemid 44382792)
28. Davidson, M. H. (2009). Pharmacological approaches to modifying HDL: more basic science to understand HDL metabolism is necessary. Editorial to: "NO-1886 up-regulates Niemann-Pick C1 protein (NPC1) expression through liver X receptor alpha signaling pathway in THP-1 macrophage-derived foam cells" by Xin Ma et al. Cardiovasc. Drugs Ther. 23, 187-188.
29. Tavridou, A., Kaklamanism, L., Papaloism, A., Kourounakis, A. P., Rekka, E. A., et al. (2007). EP2306 [2-(4-biphenyl)-4-methyl-octahydro-1,4-benzoxazin- 2-ol, hydrobromide], a novel squalene synthase inhibitor, reduces atherosclerosis in the cholesterol-fed rabbit. J. Pharmacol. Exp. Ther. 323, 794-804. (Pubitemid 350146049)
30. Gotteland, J. P., Loubat, C., Planty, B., Junquéro, D., Delhon, A., and Halazy, S. (1998). Sulfonamide derivatives of benzylamine block cholesterol biosynthesis in HepG2 cells: a new type of potent squalene epoxidase inhibitors. Bioorg. Med. Chem. Lett. 8, 1337-1342. (Pubitemid 28261298)
31. Astruc, M., Tabacik, C., Descomps, B., and de Paulet, A. C. (1977). Squalene epoxidase and oxidosqualene lanosterol-cyclase activities in cholesterogenic and non-cholesterogenic tissues. Biochim. Biophys. Acta. 487, 204-211. (Pubitemid 8071562)
32. Nakamura, Y., Sakakibara, J., Izumi, T., Shibata, A., and Ono, T. (1996). Transcriptional regulation of squalene epoxidase by sterols and inhibitors in HeLa cells. J. Biol. Chem. 271, 8053-8056. (Pubitemid 26108626)
33. Iyer, V. R., Eisen, M. B., Ross, D. T., Schuler, G., Moore, T., et al. (1999). The transcriptional program in the response of human fibroblasts to serum. Science 283, 83-87. (Pubitemid 29044852)
34. Hidaka, Y., Hotta, H., Nagata, Y., Iwasawa, Y., Horie, M., and Kamei, T. (1991). Effect of a novel squalene epoxidase inhibitor, NB-598, on the regulation of cholesterol metabolism in Hep G2 cells. J. Biol. Chem. 266, 13171-13177. (Pubitemid 21907325)
35. Chugh, A., Ray, A., and Gupta, J. B. (2003). Squalene epoxidase as hypocholesterolemic drug target revisited. Prog. Lipid Res. 42, 37-50. (Pubitemid 35428788)
36. Sawada, M., Matsuo, M., Hagihara, H., Tenda, N., Nagayoshi, A., et al. (2001). Effect of FR194738, a potent inhibitor of squalene epoxidase, on cholesterol metabolism in HepG2 cells. Eur. J. Pharmacol. 431, 11-16. (Pubitemid 33082146)
37. Nakayama, O., Hirosumi, J., Chida, N., Takahashi, S., Sawada, K., et al. (1997). FR146687, a novel steroid 5 alpha-reductase inhibitor: in vitro and in vivo effects on prostates. Prostate 31, 241-249. (Pubitemid 27247315)
38. Abe, I., Seki, T., Noguchi, H., and Kashiwada, Y. (2000). Galloyl esters from rhubarb are potent inhibitors of squalene epoxidase, a key enzyme in cholesterol biosynthesis. Planta Med. 66, 753-756. (Pubitemid 32038934)
39. Gupta, N. and Porter, T. D. (2001). Garlic and garlic-derived compounds inhibit human squalene monooxygenase. J. Nutr. 131, 1662-1667. (Pubitemid 32520429)
40. Ruf, A., Müller, F., D'Arcy, B., Stihle, M., Kusznir, E., et al. (2004). The monotopic membrane protein human oxidosqualene cyclase is active as monomer. Biochem. Biophys. Res. Commun. 315, 247-254. (Pubitemid 38183101)
41. Dehmlow, H., Aebi, J. D., Jolidon, S., Ji, Y. H., von der Mark, E. M., et al. (2003). Synthesis and structure-activity studies of novel orally active non-terpenoic 2, 3-oxidosqualene cyclase inhibitors. J. Med. Chem. 46, 3354-3370. (Pubitemid 36842420)
42. Huff, M. W. and Telford, D. E. (2005). Lord of the rings-the mechanism for oxidosqualene:lanosterol cyclase becomes crystal clear. Trends Pharmacol. Sci. 26, 335-340. (Pubitemid 40848493)
43. Hall, M. J., Nelson, L. M., Russell, R. I., and Howard, A. N. (1981). Gemfibrozil-the effect of biliary cholesterol saturation of a new lipidlowering agent and its comparison with clofibrate. Atherosclerosis 39, 511-516. (Pubitemid 11071748)
44. Telford, D. E., Lipson, S. M., Barrett, P. H., Sutherland, B. G., Edwards, J. Y., et al. (2005). A novel inhibitor of oxidosqualene:lanosterol cyclase inhibits very low-density lipoprotein apolipoprotein B100 (apoB100) production and enhances low-density lipoprotein apoB100 catabolism through marked reduction in hepatic cholesterol content. Arterioscler. Thromb. Vasc. Biol. 25, 2608-2614. (Pubitemid 43732286)
45. Billack, B., Heck, D. E., Porterfield, D. M., Malchow, R. P., Smith, P. J., et al. (2001). Minimal amidine structure for inhibition of nitric oxide biosynthesis. Biochem. Pharmacol. 61, 1581-1586. (Pubitemid 32476912)
46. Panini, S. R., Sexton, R. C., Gupta, A. K., Parish, E. J., Chitrakorn, S., and Rudney, H. (1986). Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesterol biosynthesis by oxylanosterols. J. Lipid Res. 27, 1190-1204. (Pubitemid 17233750)
47. Fouchet, M. H., Donche, F., Martin, C., Bouillot, A., Junot, C., et al. (2008). Design and evaluation of a novel series of 2, 3-oxidosqualene cyclase inhibitors with low systemic exposure, relationship between pharmacokinetic properties and ocular toxicity. Bioorg. Med. Chem. 16, 6218-6232. (Pubitemid 351758822)
48. Seo, S., Tonda, K., Uomori, A., Takeda, K., and Hirata, M. (1993). Effect of sterol biosynthesis inhibitor, SSF-109, on cholesterol synthesis in isolated rat hepatocytes. Steroids 58, 74-78.
49. Mark, M., Muller, P., Maier, R., and Eisele, B. (1996). Effects of a novel 2, 3-oxidosqualene cyclase inhibitor on the regulation of cholesterol biosynthesis in HepG2 cells. J. Lipid Res. 37, 148-158. (Pubitemid 26054359)
50. Binet, J., Thomas, D., Benmbarek, A., de, F. D., and Renaut, P. (2002). Structure activity relationships of new inhibitors of mammalian 2,3-oxidosqualene cyclase designed from isoquinoline derivatives. Chem. Pharm. Bull. (Tokyo) 50, 316-329. (Pubitemid 41685631)
51. Koh, C. H., Qi, R. Z., Qu, D., Melendez, A., Manikandan. J., et al. (2006). U18666A-mediated apoptosis in cultured murine cortical neurons: role of caspases, calpains and kinases. Cell Signal 18, 1572-1583. (Pubitemid 44216116)
52. Cenedella, R. J., Jacob, R., Borchman, D., Tang, D., Neely, A. R., et al. (2004). Direct perturbation of lens membrane structure may contribute to cataracts caused by U18666A, an oxidosqualene cyclase inhibitor. J. Lipid Res. 45, 1232-1241. (Pubitemid 38802626)
53. Pyrah, I. T., Kalinowski, A., Jackson, D., Davies, W., Davis, S., et al. (2001). Toxicologic lesions associated with two related inhibitors of oxidosqualene cyclase in the dog and mouse. Toxicol. Pathol. 29, 174-179. (Pubitemid 32531617)
54. Gerson, R. J., MacDonald, J. S., Alberts, A. W., Chen, J., Yudkovitz, J. B., et al. (1990). On the etiology of subcapsular lenticular opacities produced in dogs receiving HMG-CoA reductase inhibitors. Exp. Eye Res. 50, 65-78. (Pubitemid 20058625)
55. Cenedella, R. J. (2009). Cholesterol synthesis inhibitor U18666A and the role of sterol metabolism and trafficking in numerous pathophysiological processes. Lipids 44, 477-487.
56. Wong, J., Quinn, C. M., and Brown, A. J. (2004). Statins inhibit synthesis of an oxysterol ligand for the liver x receptor in human macrophages with consequences for cholesterol flux. Arterioscler. Thromb. Vasc. Biol 24, 2365-2371. (Pubitemid 39658043)
57. Beyea, M. M., Heslop, C. L., Sawyez, C. G., Edwards, J. Y., Markle, J. G., et al. (2007). Selective up-regulation of LXR-regulated genes ABCA1, ABCG1, and APOE in macrophages through increased endogenous synthesis of 24 (S), 25-epoxycholesterol. J. Biol. Chem. 282, 5207-5216. (Pubitemid 47093759)
58. Brown, G. R., Hollinshead, D. M., Stokes, E. S., Waterson, D., Clarke, D. S., et al. (2000). A novel series of 4-piperidinopyridine and 4-piperidinopyrimidine inhibitors of 2, 3-oxidosqualene cyclase-lanosterol synthase. J. Med. Chem. 43, 4964-4972. (Pubitemid 32039017)