Drug evaluation: TAK-475 - An oral inhibitor of squalene synthase for hyperlipidemia

Current Opinion in Investigational Drugs

Volumn 7, Issue 9, 2006, Pages 850-856

  Burnett, John R ^a  

^a ROYAL PERTH HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ANTILIPEMIC AGENT; ATORVASTATIN; BMS 187745; BMS 188494; CHOLESTEROL; EP 2300; EP 2302; EP 2306; ER 27856; ER 28448; EZETIMIBE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; PHOSPHOLIPID; ROSUVASTATIN; RPR 107393; SIMVASTATIN; SQUALENE SYNTHASE; SQUALENE SYNTHASE INHIBITOR; T 91485; TAK 475; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; YM 53601;

ACIDOSIS; ACUTE KIDNEY FAILURE; ATHEROSCLEROSIS; CLINICAL TRIAL; DISEASE MODEL; DRUG ABSORPTION; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG HYDROLYSIS; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENTIATION; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; GASTROINTESTINAL SYMPTOM; HEADACHE; HUMAN; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; ISCHEMIC HEART DISEASE; LIVER TOXICITY; MUSCLE DISEASE; MUSCLE WEAKNESS; MYALGIA; MYOGLOBINURIA; MYOPATHY; MYOSITIS; NONHUMAN; REVIEW; RHABDOMYOLYSIS; STRUCTURE ACTIVITY RELATION; TOXICITY TESTING;

ANIMALS; ANTILIPEMIC AGENTS; CLINICAL TRIALS, PHASE I; CLINICAL TRIALS, PHASE II; CLINICAL TRIALS, PHASE III; ENZYME INHIBITORS; FARNESYL-DIPHOSPHATE FARNESYLTRANSFERASE; HUMANS; OXAZEPINES; PIPERIDINES; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33748646581     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (48)

1. α-Phosphonosulfonic acids: Potent and selective inhibitors of squaline synthase. Magnin DR, Biller SA, Chen Y, Dickson JK Jr, Fryszman OM, Lawrence RM, Logan JV, Sieber-McMaster ES, Sulsky RB, Traeger SC, Hsieh DC et al J MED CHEM 1996 39 3 657-660
2. HMG-CoA reductase inhibitors: A look back and a look ahead. Davignon J, Montigny M, Dufour R CANADIAN J CARDIOL 1992 8 8 843-864
3. Regulation of the mevalonate pathway. Goldstein JL, Brown MS NATURE 1990 343 6257 425-430
4. Inhibition of cholesterol synthesis by squalene synthase inhibitors does not induce myotoxicity in vitro. Flint OP, Masters BA, Gregg RE, Durham SK TOXICOL APPL PHARMACOL 1997 145 1 91-98
5. Effect of ER-27856, a novel squalene synthase inhibitor, on plasma cholesterol in rhesus monkeys: Comparison with 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors. Hiyoshi H, Yanagimachi M, Ito M, Ohtsuka I, Yoshida I, Saeki T, Tanaka H J LIPID RES 2000 417 1136-1144
6. Novel 4,1-benzoxapine derivatives with potent squalene synthase inhibitory activities. Miki T, Kori M, Mabuchi H, Banno H, Tozawa R, Nakamura M, Itokawa S, Sugiyama Y, Yukimasa H BIOORG MED CHEM 2002 10 2 401-414
7. Syntheses of fused heterocyclic compounds and their inhibitory activities for squalene synthase. Miki T, Kori M, Fujishima A, Mabuchi H, Tozawa RI BIOORG MED CHEM 2002 10 2 385-400
8. Synthesis of novel 4,1-benzoxazepine derivatives as squalene synthase inhibitors and their inhibition of cholesterol synthesis. Miki T, Kori M, Mabuchi H, Tozawa R-I, Nishimoto T, Sugiyama Y, Teshima K, Yukimasa H J MED CHEM 2002 46 20 4571-4580
9. Lipid-lowering effects of TAK-475, a squalene synthase inhibitor, in animal models of familial hypercholesterolemia. Amano Y, Nishimoto T, Tozawa R-I, Ishikawa E, Imura Y, Sugiyama Y EUR J PHARMACOL 2003 466 1-2 155-161
10. Commentary: Squalene synthase inhibitors. Menys VC, Durrington PN BR J PHARMACOL 2003 139 5 881-882
11. Lipid-lowering properties of TAK-475, a squalene synthase inhibitor, in vivo and in vitro. Nishimotot T, Amano Y, Tozawa R, Ishikawa E, Imura Y, Hidefumi H, Sugiyama Y BR J PHARMACOL 2003 139 5 911-918
12. Effect of YM-53601, a novel squalene synthase inhibitor, on the clearance rate of plasma LDL and VLDL in hamsters. Ugawa T, Kakuta H, Moritani H, Inagaki O BR J PHARMACOL 2002 137 4 561-569
13. YM-53601, a novel squalene synthase inhibitor, suppresses lipogenic biosynthesis and lipid secretion in rodents. Ugawa T, Kakuta H, Moritani H, Inagaki O, Shikama H BR J PHARMACOL 2003 139 1 140-146
14. Ezetimibe: A first-in-class, novel cholesterol absorption inhibitor. Lipka LJ CARDIOVASC DRUG REV 2003 21 4 293-312
15. Takeda: Product pipeline. Takeda Pharmaceutical Co Ltd COMPANY WORLD WIDE WEB SITE 2005 March 31 www.takeda.co.jp
16. Squalene synthase inhibitors reduce plasma triglyceride through a low-density lipoprotein receptor-independent mechanism. Hiyoshi H, Yanagimachi M, Ito M, Saeki T, Yoshida I, Okada T, Ikuta H, Shinmyo D, Tanaka K, Kurusu N, Tanaka H EUR J PHARMACOL 2001 431 3 345-352
17. Squalene synthase inhibitors suppress triglyceride biosynthesis through the farnesol pathway in rat hepatocytes. Hiyoshi H, Yanagimachi M, Ito M, Yasuda N, Okada T, Ikuta H, Shinmyo D, Tanaka K, Kurusu N, Yoshida I, Abe S et al J LIPID RES 2003 44 1 128-135
18. Syntheses of (4,1-benzoxazepine-3-ylidene)acetic acid derivatives and their inhibition of squalene synthase. Miki T, Kori M, Tozawa R, Nakamura M, Sugiyama Y, Yukimasa H CHEM PHARM BULL TOKYO 2002 50 1 53-58
19. Effect of TAK-475 with or without ezetimibe versus ezetimibe alone in patients with primary dyslipidemia needing to reduce their low-density cholesterol ("bad" cholesterol). INTERNET SITE 2005 December 20
20. Effect of TAK-475 in diabetes patients needing to reduce their low-density cholesterol ("bad" cholesterol). INTERNET SITE 2005 November www.clinicaltrials.gov
21. Effect of TAK-475, when given with simvastatin, in patients needing to reduce their low-density cholesterol ("bad" cholesterol). INTERNET SITE 2005 October www.clinicaltrials.gov
22. Effect of TAK-475 and simvastatin alone or in combination on blood cholesterol levels. INTERNET SITE 2006 February www.clinicaltrials.gov
23. Effect of TAK-475 or placebo on blood cholesterol levels in subjects co-administered rosuvastatin. INTERNET SITE 2005 November www.clinicaltrials.gov
24. Effect of TAK-475 or placebo on blood cholesterol levels in subjects co-administered high-dose statin. INTERNET SITE 2006 November www.clinicaltrials.gov
25. Effect of TAK-475 or placebo co-administered with current lipid-lowering treatment on blood cholesterol levels in subjects with homozygous familial hypercholesterolemia. INTERNET SITE 2005 December www.clinicaltrials.gov
26. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and hepatic apolipoprotein B secretion. Huff MW, Burnett JR CURR OPIN LIPIDOL 1997 8 3 138-145
27. Sterols and isoprenoids: Signaling molecules derived from the cholesterol biosynthetic pathway. Edwards PA, Ericsson J ANNU REV BIOCHEM 1999 68 157-185
28. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. Pasternak RC, Smith SC Jr, Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C J AM COLL CARDIOL 2002 40 3 567-572
29. Structure and regulation of mammalian squalene synthase. Tansey TR, Shechter I BIOCHIM BIOPHYS ACTA 2000 1529 1-3 49-62
30. Localisation of the squalene synthase gene (FDFT1) to human chromosome 8p22-p23.1. Schechter I, Conrad DG, Hart I, Berger RC, McKenzie TL, Bleskan J, Patterson D GENOMICS 1994 20 1 116-118
31. Molecular cloning and functional analysis of the promoter of the human squalene synthase gene. Guan G, Jiang G, Koch RL, Shechter I J BIOL CHEM 1995 270 37 21958-21965
32. Differential transcriptional regulation of the human squalene synthase gene by sterol regulatory element-binding proteins (SREBP) 1a and 2 and involvement of 5′ DNA sequence elements in the regulation. Guan G, Dai P, Shechter I J BIOL CHEM 1997 273 20 12526-12535
33. Squalene synthase inhibitors: Their potential as hypocholesterolaemic agents. Watson NS, Procopiou PA PROG MED CHEM 1996 33 331-378
34. Comparing myotoxic effects of squalene synthase inhibitor, T-91485, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in human myocytes. Nishimoto T, Tozawa R, Amano Y, Wada T, Imura Y, Sugiyama Y BIOCHEM PHARMACOL 2003 66 11 2133-2139
35. Orally active squalene synthase inhibitors: Bis((acyloxy)alkyl) prodrugs of the α-phosphonosulfonic acid moiety. Dickson JK Jr, Biller SA, Magnin DR, Petrillo EW Jr, Hillyer JW, Hsieh DC, Lan SJ, Rinehart JK, Gregg RE, Harrity TW, Jolibois KG et al J MED CHEM 1996 39 3 661-664
36. Pharmacological characterization in vitro of EP2306 and EP2302, potent inhibitors of squalene synthase and lipid biosynthesis. Tavridou A, Kaklamanis L, Megaritis G, Kourounakis AP, Papalois A, Roukounas D, Rekka EA, Kourounakis PN, Charalambous A, Manolopoulos VG EUR J PHARMACOL 2006 536 1-3 34-42
37. A novel squalene synthase inhibitor: Lipid lowering properties in animal models. Nishimoto T, Amano Y, Tozawa R ATHEROSCLER SUPPL 2006 7 339
38. Stabilization of coronary atherosclerosis by a squalene synthase inhibitor. Shiomi M, Yamada S, Amano Y, Nishimoto T, Ito T ATHEROSCLER SUPPL 2006 7 339
39. Hypolipidemic and anti-atherosclerotic effects of a squalene synthase inhibitor, TAK-475, in WHHLMI rabbits. Shiomi M, Yamada S, Amano Y, Nishimoto T, Ito T ATHEROSCLER SUPPL 2006 7 549
40. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Grundy SM, Cleeman JI Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ CIRCULATION 2004 110 2 227-239
41. Rationale for combination therapy with statin drugs in the treatment of dyslipidemia. Ansell BJ CURR ATHEROSCLEROSIS REP 2005 7 1 29-33
42. Lipid-lowering therapies in development. Werzbicki AS EXPERT OPIN INVEST DRUGS 2004 13 11 1405-1418
43. Effect of TAK-475 or placebo on blood cholesterol levels in subjects with elevated cholesterol. INTERNET SITE 2005 December www.clinicaltrials.gov
44. Farnesol-derived dicarboxylic acids in the urine of animals treated with zaragozic acid A or with farnesol. Bostedor RG, Karkas JD, Arison BH, Bansal VS, Vaidya S, Germershausen JI, Kurtz MM, Bergstrom JD J BIOL CHEM 1997 272 14 9197-203
45. Rationale for targeting multiple lipid pathways for optimal cardiovascular risk reduction. Ballantyne CM AM J CARDIOL 2005 96 9A 14K-19K
46. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. McKenney JM, Davidson MH, Jacobson TA, Guyton JR, National Lipid Association Statin Safety Assessment Task Forte AM J CARDIOL 2006 87 8A 89C
47. Pharmaceuticals sector: Initiating coverage: Neutral on the sector. Masuzoe K DEUTSCHE SECURITIES LIMITED 2005 September 30
48. Possible lull in share price gains; initiate with neutral rating and ¥95,900 target price. Sakai F CREDIT SUISSE FIRST BOSTON 2005 August 05