Avasimibe: Pfizer

Current Opinion in Investigational Drugs

Volumn 3, Issue 9, 2002, Pages 1328-1333

  Burnett, John R ^a,b   Huff, Murray W ^c  

^a ROYAL PERTH HOSPITAL   (Australia)

^b UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^c ROBARTS RESEARCH INSTITUTE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ACYL COENZYME A; ANTILIPEMIC AGENT; AVASIMIBE; CHOLESTEROL ACYLTRANSFERASE INHIBITOR; ENZYME INHIBITOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; PD 148515; PLACEBO;

ADRENAL DISEASE; ATHEROSCLEROSIS; BLOOD TOXICITY; CLINICAL TRIAL; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG COST; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG MEGADOSE; DRUG METABOLISM; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TOLERABILITY; DRUG TOXICITY; ERYTHROCYTE; FOOD DRUG INTERACTION; HUMAN; HYPERLIPIDEMIA; HYPOCHOLESTEROLEMIA; LIVER TOXICITY; NONHUMAN; PLASMA HALF LIFE; REVIEW; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ACETATES; ANIMALS; ARTERIOSCLEROSIS; CLINICAL TRIALS; DRUG INDUSTRY; ENZYME INHIBITORS; HUMANS; HYPERLIPIDEMIAS; SULFONIC ACIDS;

EID: 0036771284     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (27)

1. 232635 Inhibitors of acyl-CoA: cholesterol O-acyltransferase (ACAT) as hypocholesterolemic agents. CI-1011: An acyl sulfamate with unique cholesterol-lowering activity in animals fed noncholesterol-supplemented diets. Lee HT, Sliskovic DR, Picard JA, Roth BD, Wierenga W, Hicks JL, Bousley RF, Hamalehlee KL, Homan R, Speyer C, Stanfield RL, Krause BR J Med Chem 1996 39 26 5031-5034. This report describes the rationale and synthetic route for avasimibe, as well as its lipid lowering effects in small animal models.
2. 273169 ACAT inhibition by CI-1011 lowers plasma triglycerides in rats by enhancing the clearance of VLDL. Krause BR, Auerbach BJ Atherosclerosis 1997 134 1-2 128
3. 278026 Inhibitors of acyl-CoA: cholesterol O-acyltransferase (ACAT) as hypercholesterolemic agents: Synthesis and structure-activity relationships of novel series of sulfonamides, acylphosphonamides and acylphosphoramidates. Lee HT, Roark WH, Picard JA, Sliskovic DR, Roth BD, Stanfield RL, Hamalehle KL, Bousley RF, Krause BR Bioorg Med Chem Lett 1998 8 3 289-294
4. 280913 Clinical pharmacokinetics of CI-1011, an ACAT inhibitor. Vora J, Stern R, Lathia C Pharm Res 1997 14 11 Suppl S505
5. 286139 CI-1011 lowers lipoprotein(a) and plasma cholesterol concentrations in chow-fed cynomolgus monkeys. Ramharack R, Spahr MA, Sekerke CS, Stanfield RL, Bousley RF, Lee HT, Krause BK Atherosclerosis 1998 136 1 79-87. This paper reports a significant reduction in Lp(a) in response to avasimibe treatment, possibly due to a reduction in hepatic synthesis. Total serum cholesterol was also reduced, but serum TG was unaffected.
6. 286516 Warner-Lambert forecasts 35% earnings growth. SCRIP 1998 April 29 2330 8
7. 309359 The ACAT inhibitor, CI-1011 is effective in the prevention and regression of aortic fatty streak area in hamsters. Nicolosi RJ, Wilson TA, Krause BR Atherosclerosis 1998 137 1 77-85
8. 316521 US Investment Research: Warner Lambert. Morgan Stanley Dean Witter 1999 February 09
9. 325742 ApoB100 secretion from HepG2 cells is decreased by the ACAT inhibitor CI-1011: An effect associated with enhanced intracellular degradation of ApoB. Wilcox LJ, Barrett PHR, Newton RS, Huff MW Arterioscler Thromb Vasc Biol 1999 19 4 939-949. This report describes in vitro studies in HepG2 cells showing that avasimibe decreases hepatic apoB secretion and enhances apoB degradation.
10. 330916 Drug development pipeline. Lambert Co Company Communication 1999 July 08
11. 355825 Inhibition of ACAT by avasimibe decreases both VLDL and LDL apolipoprotein B production in miniature pigs. Burnett JR, Wilcox LJ, Telford DE, Kleinstiver SJ, Barrett PHR, Newton RS, Huff MW J Lipid Res 1999 40 7 1317-1327. This report describes in vivo apoB turnover studies showing that avasimibe decreases both VLDL and LDL apoB production in the miniature pig.
12. 355828 Acyl-coenzyme A:cholesterol acyltransferase inhibitor, avasimibe, stimulates bile acid synthesis and cholesterol 7α-hydroxylase in cultured rat hepatocytes and in vivo in the rat. Post SM, Zoeteweij JP, Bos MH, De Wit EC, Havinga R, Kuipers F, Princen HM Hepatology 1999 30 2 491-500. This report describes the effect of avasimibe in stimulating bile acid synthesis and cholesterol 7α-hydroxylase in primary rat hepatocytes and in vivo.
13. 357788 US drug industry Rx insight. Lehman Brothers Inc 2000 January 18 1-303
14. 371470 FTC grants final clearance for Pfizer/Warner-Lambert merger, transaction completed today. Pfizer Inc Press Release 2000 June 19
15. 375962 US major pharmaceutical model and pipeline book: 1st Quarter 2000 issue. Merrill Lynch Capital Markets 2000 May
16. 393182 Pfizer sees sustained, strong performance as broad and deep product line, new product pipeline, profit margin expansion and strategic alliances drive growth. Pfizer Inc Press Release 2000 December 11
17. 399484 Equity Research: Bristol-Myers Squibb. Credit Suisse First Boston 2001 February 06
18. 399956 Wall Street analysis meeting. Pfizer Inc Company Communication 2000 December 11
19. 415320 Preclinical safety evaluation of avasimibe in beagle dogs: An ACAT inhibitor with minimal adrenal effects. Robertson DG, Breider MA, Milad MA Toxicol Sci 2001 59 324-334
20. 420283 Efficacy and short-term safety of a new ACAT inhibitor, avasimibe, on lipids, lipoproteins, and apolipoproteins, in patients with combined hyperlipidemia. Insull WJR, Koren M, Davignon J, Sprecher D, Schrott H, Keilson LM, Brown AS, Dujovne CA, Davidson MH, McLain R, Heinonen T Atherosclerosis 2001 157 1 137-144 This report describes a double-blind, randomized, placebo-controlled phase II trial of avasimibe (50, 125, 250 or 500 mg/day) for 8 weeks in 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia.
21. 420809 Pharmaceutical Desk Reference: Global equities research US - Our models of the major US pharma companies. Lehman Brothers Inc 2001 August
22. 422318 Credit Suisse First Boston - Pfizer: Company update. Credit Suisse First Boston 2001 August 28
23. 427113 Healthcare: Pharmaceuticals: Pharmaceutical industry review. Rubin J, Yu N, Sone T Morgan Stanley Dean Witter 2001 September 27
24. 428395 Annual Report 2000: Life is our life's work. Pfizer Inc Annual Report 2001 February 22
25. 429152 Pipeline Pulse: 1000+ drugs in development provide bright future for industry. Scala SM, Sanderson IC, Moran JR, Cacciatore KC, Perreault JB SG Cowen Securities Corporation 2001 October
26. 440208 PDR January 2002. Butler CA Lehman Brothers Inc 2002 February 01
27. 455699 Anti-atherogenic feects of the acyl-CoA:Cholesterol acyltransferase inhibitor, avasimibe (Cl-1011), in cultured primary human macrophages. Rodriguez A, Usher DC Atherosclerosis 2002 161 1 45-54