Avasimibe. Treatment of lipoprotein disorders, ACAT inhibitor

Drugs of the Future

Volumn 24, Issue 1, 1999, Pages 9-15

  Sorbera, L A ^a   Rabasseda, X ^a   Castaner J ^a  

^a PROUS SCIENCE   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ANTILIPEMIC AGENT; AVASIMIBE; CHOLESTEROL ACYLTRANSFERASE INHIBITOR; CI 999; SULFAMIC ACID ((2,4,6 TRIS (1 METHYLETHYL) PHENYL)ACETYL) 2,6 BIS(1 METHYLETHYL) PHENYL ESTER; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL MODEL; ARTICLE; ATHEROSCLEROSIS; CHOLESTEROL BLOOD LEVEL; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; HYPERTRIGLYCERIDEMIA; LIPOPROTEIN BLOOD LEVEL; LIPOPROTEIN METABOLISM; MAJOR CLINICAL STUDY; MULTICENTER STUDY; NONHUMAN; ORAL DRUG ADMINISTRATION; RANDOMIZED CONTROLLED TRIAL; RAT;

EID: 0032992184     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.1999.024.01.474029     Document Type: Article

References (41)

1. Dozeman, G.J., Fiore, P.J., Puls, T.P., Walker, J.C. Chemical development of a pilot scale for the ACAT inhibitor 2,6-diisopropylphenyl [(2,4,6-triisopropylphenyl)acetyl]sulfamate. Org Process Res Dev 1997, 1: 137-48.
2. Lee, H.T., Sliskovic, D.R., Picard, J.A. et al. Inhibitors of acyl-CoA:cholesterol O-acyl transferase (ACAT) as hypocholesterolemic agents. Cl-1011: An acyl sulfamate with unique cholesterol-lowering activity in animals fed noncholesterolsupplemented diets. J Med Chem 1996, 39: 5031-4.
3. Sliskovic, D.R. Cl-1011: An atypical ACAT inhibitor with antiatherosclerotic activity. In: Proceedings of the XIVth International Symposium on Medicinal Chemistry, Maastricht, 8-12 September 1996, Awouters, F. (Ed.), Elsevier Science B.V., Amsterdam, 1997, 433-41.
4. Lee, H.T., Picard, J.A., Sliskovic, D.R., Wierenga, W. (Warner-Lambert Co.). N-Acyl sulfamic acid esters (or thioesters), N-acyl sulfonamides, and N-sulfonyl carbamic acid esters (or thioesters) as hypercholesterolemic agents. EP 698010, JP 96510256, US 5491172, WO 9426702.
5. Sorbera, L.A., Silvestre, J., Castañer, J. F-1394. Drugs Fut 1998, 23: 712-7.
6. Sliskovic, D.R., Krause, B.R., Picard, J.A., Anderson, M., Bousley, R.F., Hamelehle, K.L., Homan, R., Julian, T.N., Rashidbaigi, Z.A., Stanfield, R.L. Inhibitors of acyl-CoA:cholesterol O-acyltransferase (ACAT) as hypocholesterolemic agents. 6. The first water-soluble ACAT inhibitor with lipid-regulating activity. J Med Chem 1994, 37: 560-2.
7. Robertson, D.G., Krause, B.R., Welty, D.R, Wolfgang, G.H.I., Graziano, M.J., Pincher, G.D., Urda, E. Hepatic microsomal induction profile of carbamic acid [[2,6-bis(1-methyl ethyl)-phenoxy]sulfonyl]-2,6-bis(1-methylethyl)phenyl ester, monosodium salt (PD 138142-15), a novel lipid regulating agent. Biochem Pharmacol 1995, 49: 799-808.
8. Lee, H.T., Roark, W.H., Picard, J.A., Sliskovic, D.R., Roth, B.D., Stanfield, R.L, Hamelehle, K.L., Bousley, R.F., Krause, B.R. Inhibitors of acyl-CoA:cholesterol O-transferase (ACAT) as hypocholesterolemic agents: Synthesis and structure-activity relationships of novel series of sulfonamides, acylphosphonamides and acylphosphoramidates. Bioorg Med Chem Lett 1998, 8: 289-94.
9. Post, S.M., Zoeteweij, J.P., Bos, M.A.H., de Wit, E.C.M., Princen, H.M.G. ACAT inhibitor Cl-1011 stimulates bile acid synthesis and cholesterol 7alpha-hydroxylase in cultured rat hepatocytes and in vivo in rat. 13th Int Symp Drugs Affect Lipid Metab (May 30-June 3, Florence) 1998, 15.
10. Wilcox, L.J., Barrett, P.H.R., Newton, R.S., Huff, M.W. The ACAT inhibitor Cl-1011 inhibits apoB secretion in HepG2 cells: An effect associated with enhanced rapid intracellular degradation and decreased MTP expression. Circulation 1998, 98(17, Suppl.): Abst 2047.
11. Cullen, P., Cignarella, A., Assmann, G. Effect of atorvastatin, the ACAT inhibitor Cl-1011 and progesterone on storage and secretion of cholesterol in human monocyte-derived macrophages. Circulation 1998, 98(17, Suppl.): Abst 2828.
12. Lee, H.T., Picard, J.A., Sliskovic, D.R., Roth, B.D., Hamelehle, K.L., Bousley, R.F., Krause, B.R., Stanfield, R.L. Cl-1011: A potent lipid regulating agent. 12th Int Symp Drugs Affect Lipid Metab (Nov 7-10, Houston) 1995, 101.
13. Krause, B.R., Auerbach, B.J. ACAT inhibition by Cl-1011 lowers plasma triglycerides in rats by enhancing the clearance of VLDL Atherosclerosis 1997, 134(1-2): Abst 2.P.55.
14. Nicolosi, R.J., Wilson, T.A., Krause, B.R. The ACAT inhibitor, Cl-1011 is effective in the prevention and regression of aortic fatty streak area in hamsters. Atherosclerosis 1998, 137: 77-85.
15. Homan, R., Auerbach, B.J., Krause, B.R. Gallstones prevented by the ACAT inhibitor Cl-1011 in hamsters fed a lithogenic diet. 13th Int Symp Drugs Affect Lipid Metab (May 30-June 3, Florence) 1998, 48.
16. Auerbach, B.J., Bousley, R.F., Stanfield, R.L., Bisgaier, C.L., Homan, R., Krause, B.R. Modulation of apoB kinetics and lipoprotein cholesterol in the casein-fed rabbit by Cl-1011: In vivo evidence for liver ACAT inhibition. 12th Int Symp Drugs Affect Lipid Metab (Nov 7-10, Houston) 1995, 135.
17. Bocan, T.M.A., Rosebury, W.S., Lu, X., Dagle, C., Bak-Mueller, S. Coadministration of the ACAT inhibitor, Cl-1011, and simvastatin induces atherosclerotic lesion regression. Circulation 1998, 98(17, Suppl.): Abst 1624.
18. Bocan, T.M.A., Rosebury, W.S., Bak Mueller, S. HMG-CoA reductase and ACAT inhibitors act synergistically to lower plasma cholesterol and limit atherosclerotic lesion formation in the rabbit. Atherosclerosis 1997, 134(1-2): Abst 2.P.20.
19. Kurz, S., Borthayre, A.B., Harrison, D.G. The effect of ACAT inhibition with avasimibe on vascular function in hypercholesterolemia. Circulation 1998, 98(17, Suppl.): Abst 558.
20. Burnett, J.R., Wilcox, L.J., Telford, D.E., Kleinstiver, S.J., Barrett, RH.R., Newton, R.S., Huff, M.W. Inhibition of ACAT by Cl-1011, in vivo, decreases both VLDL and LDL apoB production in the miniature pig. Atherosclerosis 1997, 134(1-2): Abst 4.P.251.
21. Ramharack, R., Spahr, M.A., Sekerke, C.S., Stanfield, R.L, Bousley, R.F., Lee, H.T., Krause, B.K. Cl-1011 lowers lipoprotein(a) and plasma cholesterol concentrations in chow-fed cynomolgus monkeys. Atherosclerosis 1998, 136: 79-87.
22. Hrzenjak, A., Frank, S., Krause, B.R., Ramharack, R., Kostner, G.M. Influence of Cl-1011 on lipoprotein(a) [Lp(a)] level in transgenic mice 13th Int Symp Drugs Affect Lipid Metab (May 30-June 3, Florence) 1998, 12.
23. Bullen, W.W., Lathia, C.D., Abel, R.B., Hayes, R.N. Validated HPLC/MS/MS assay for Cl-1011 in rat plasma and a comparison with an HPLC/UV assay. J Pharm Biomed Anal 1998, 17: 1399-413.
24. Lathia, C.D., Hollembaek, J., Hayes, R., Lilley, B., Harvan, D. Validation of Cl-1011 in human plasma by a HPLC/MS/MS assay to support phase I pharmacokinetic studies. Pharm Res 1997, 14(11, Suppl.): Abst 2132.
25. Milad, M.A., Krause, B.R., Bullen, W.W., Mueller, K.R., Lathia, C.D. Relative bioavailability and efficacy of Cl-1011 in a nanoparticle suspension compared to a conventional suspension. Pharm Res 1997, 14(11, Suppl.): Abst 2097.
26. Lathia, C.D., Robertson, D.O., Milad, M.A. Single and multiple dose pharmacokinetics of Cl-1011, a lipid lowering agent, in the rat. Pharm Res 1996, 13(9, Suppl.): Abst PPDM 8428.
27. Shum, Y., Whitfield, L., Robertson, D., Lathia, C. Plasma concentration and toxicokinetic characteristics of Cl-1011 in rodents following multiple oral dosing. Pharm Res 1997, 14(11, Suppl.): Abst 2429.
28. Milad, M.A., Robertson, D.G., Lathia, C.D. Single and multiple dose pharmacokinetics of Cl-1011 in dogs. Pharm Res 1996, 13(9, Suppl.): Abst PPDM 8353.
29. Vora, J., Stern, R., Lathia, C. Clinical pharmacokinetics of Cl-1011, an ACAT inhibitor. Pharm Res 1997, 14(11, Suppl.): Abst 3111.
30. Koren, M., Insull, W. Jr., Schrott, H., Davila, M., Heinone, T., McLain, R.W., Black, D. ACAT inhibitor avasimibe lowers VLDL and TG in patients with hypertriglyceridemia. Circulation 1998, 98(17, Suppl.): Abst 1243.
31. Ramharack, R., Spahr, M.S., Stanfield, R.L., Bousley, R.F., Lee, H.T., Krause, B.R. Cl-1011 decreases cynomolgus monkey plasma lipoprotein(a) levels. 12th Int Symp Drugs Affect Lipid Metab (Nov 7-10, Houston) 1995, 55.
32. Lathia, C.D., Robertson, D.G., Milad, M.A. Single and multiple dose pharmacokinetics of Cl-1011, an in vivo ACAT inhibitor, in rat. 12th Int Symp Drugs Affect Lipid Metab (Nov 7-10, Houston) 1995, 99.
33. Hui, Y.F., Milad, M.A., Robertson, D.G., Lathia, C.D. Pharmacokinetics and pharmacodynamics in a 2-week study in beagle dogs of Cl-1011, an in vivo ACAT inhibitor. 12th Int Symp Drugs Affect Lipid Metab (Nov 7-10, Houston) 1995, 99.
34. Milad, M.A., Robertson, D.G., Lathia, C.D. Single and multiple dose pharmacokinetics in dogs of Cl-1011, an in vivo ACAT inhibitor. 12th Int Symp Drugs Affect Lipid Metab (Nov 7-10, Houston) 1995, 99.
35. Bocan, T.M.A., Rosebury W., Bak Mueller, S., Lee, P., Kuchera, S., Lee, H. Cl-1011, an ACAT inhibitor with paradoxical antiatherosclerotic activity. 12th Int Symp Drugs Affect Lipid Metab (Nov 7-10, Houston) 1995, 132.
36. Krause, B.R., Pape, M., Rea, T., Bousley, R., Stanfield, R., Kieft, K., Anderson, M.K., Lee, H., Homan, R. Cl-1011: A novel cholesterol-lowering compound in both chow-fed and cholesterol-fed rodent and nonrodent species. 12th Int Symp Drugs Affect Lipid Metab (Nov 7-10, Houston) 1995, 136.
37. Laitinen, L., Nicolosi, R.J., Krause, B.R. The ACAT inhibitor, Cl-1011 is effective in the prevention and regression of atherogenesis in hamsters. FASEB J 1996, 10(3): Abst 2943.
38. Krause, B.R., Homan, R., Bocan, T.M.A., Rea, T., Pape, M., Ramharack, R., Auerbach, B., Bisgaier, C.J., Newton, R.S. Cl-1011: Unexpected preclinical pharmacologic profile for an ACAT inhibitor. 66th Cong Eur Atheroscler Soc (July 13-17, Florence) 1996, 8.
39. Burnett, J.R., Wilcox, L.J., Telford, D.E., Kleinstiver, S.J., Barrett, P.H.R., Newton, R.S., Huff, M.W. Hepatic apolipoprotein B secretion, in vivo, is decreased by the ACAT inhibitor Cl-1011 in miniature pigs. Circulation 1997, 96(8, Suppl.): Abst 3042.
40. Wilcox, L.J., Burnett, J.R., Newton, R.S., Huff, M.W. The ACAT inhibitor Cl-1011 decreases apoB secretion from HepG2 cells, an effect unrelated to the rate of cholesterol esterification. 13th Int Symp Drugs Affect Lipid Metab (May 30-June 3, Florence) 1998, 25.
41. Kulinski, A., Dulay, D., Macri, J., Newton, R., Krause, B., Adeli, K. Effects of Cl-1011 on the assembly and secretion of apolipoprotein B-containing lipoproteins in HepG2 cells. 13th Int Symp Drugs Affect Lipid Metab (May 30-June 3, Florence) 1998, 76.