AGI-1067: A multifunctional phenolic antioxidant, lipid modulator, anti-inflammatory and antiatherosclerotic agent

Journal of Pharmacology and Experimental Therapeutics

Volumn 305, Issue 3, 2003, Pages 1116-1123

  Sundell, Cynthia L ^a   Somers, Patricia K ^a   Meng, Charles Q ^a   Hoong, Lee K ^a   Suen, Ki Ling ^a   Hill, Russell R ^a   Landers, Laura K ^a   Chapman, Angela ^a   Butteiger, Dustie ^b   Jones, Moira ^c   Edwards, David ^a   Daugherty, Alan ^b   Wasserman, Martin A ^a   Alexander, R Wayne ^d   Medford, Russell M ^a   Saxena, Uday ^a,e  

^a AtheroGenics Inc   (United States)

^b UNIVERSITY OF KENTUCKY   (United States)

^c IQVIA   (United States)

^d EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e Reddy US Therapeutics   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

[4 [[1 [[3,5 BIS(1,1 DIMETHYLETHYL) 4 HYDROXYPHENYL]THIO] 1 METHYLETHYL]THIO] 2,6 BIS(1,1 DIMETHYLETHYL)PHENYL]ESTER; ANTIINFLAMMATORY AGENT; ANTILIPEMIC AGENT; ANTIOXIDANT; APOLIPOPROTEIN E; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LIPOPOLYSACCHARIDE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN RECEPTOR; MESSENGER RNA; MONOCYTE CHEMOTACTIC PROTEIN 1; PHENOL DERIVATIVE; PROBUCOL; PROBUCOL SUCCINATE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VASCULAR CELL ADHESION MOLECULE 1;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; AORTA; ARTICLE; ATHEROSCLEROSIS; BLOOD VESSEL WALL; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; CORONARY ARTERY; CORONARY ARTERY DISEASE; DOSE RESPONSE; DRUG EFFICACY; DRUG MECHANISM; DRUG TOLERABILITY; ENDOTHELIUM CELL; GENE EXPRESSION; HISTOPATHOLOGY; HUMAN; HUMAN CELL; HYPERCHOLESTEROLEMIA; KNOCKOUT MOUSE; LIPOPROTEIN BLOOD LEVEL; MALE; MONKEY; MOUSE; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTICHOLESTEREMIC AGENTS; ANTIOXIDANTS; ARTERIOSCLEROSIS; DISEASE MODELS, ANIMAL; ENDOTHELIUM, VASCULAR; HUMANS; LIPID METABOLISM; MACACA FASCICULARIS; MICE; MICE, INBRED C57BL; OXIDATION-REDUCTION; PROBUCOL;

EID: 0038476498     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: 10.1124/jpet.102.048132     Document Type: Article

References (37)

1. Aiello RJ, Bourassa PA, Lindsey S, Weng W, Natoli E, Rollins BJ, and Milos PM (1999) Monocyte chemoattractant protein-1 accelerates atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 19:1518-1525.
2. Brown MS and Goldstein J (1975) Regulation of the activity of the low-density lipoprotein receptor in human fibroblasts. Cell 6:307-316.
3. Christen WG and Hennekens CH (2000) Antioxidant vitamins and cardiovascular disease: evidence from observational epidemiologic studies and randomized trials, in Antioxidants and Cardiovascular Disease (Tardiff JC and Bourassa MG ed) pp135-143, Kluwer Academic Publishers, Norwell, MA.
4. Cybulsky MI, Iiyama K, Li H, Zhu S, Chen M, Iiyama M, Davis V, Ramos Gutierrez JC, Connelly PW, and Milstone DS (2001) A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Investig 107:1209-1210.
5. Dansky HM, Barlow CB, Lominska C, Sikes JL, Kao C, Weinsaft J, Cybulsky MI, and Smith JD (2001) Adhesion of monocytes to arterial endothelium and initiation of atherosclerosis are critically dependent on vascular cell adhesion molecule-1 gene dosage. Arterioscler Thromb Vasc Biol 21:1662-1667.
6. Daugherty A, Pure E, Delfel-Butteiger D, Chen S, Leforovich J, Roselaar SE, and Rader DJ (1997) The effects of total lymphocyte deficiency on the extent of atherosclerosis in apolipoprotein E -/- mice. J Clin Investig 100:1575-1580.
7. Daugherty A and Roselaar SE (1995) Lipoprotein oxidation as a mediator of atherogenesis: insights from pharmacological studies. Cardiovasc Res 29:297-311.
8. Gosling J, Slaymaker S, Gu L, Tseng S, Zlot CH, Young SG, Rollins BJ, and Charo IF (1999) MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B. J Clin Investig 103:773-778.
9. Horkko S, Bird DA, Miller E, Itabe H, Leitinger N, Subbanagounder G, Berliner JA, Freidman P, Dennis EA, Curtiss LK, et al. (1999) Monoclonal antibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low-density lipoproteins. J Clin Investig 103:117-128.
10. Iiyama K, Hajra L, Iiyama M, Li H, DiChiara M, Medoff BD, and Cybulsky MI (1999) Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. Circ Res 85:199-207.
11. Innis-Whitehouse W, Li X, Brown VW, and Le N (1998) An efficient chromatographic system for lipoprotein fractionation using whole plasma. J Lipid Res 39:679-690.
12. Ishibashi S, Goldstein JL, Brown MS, Herz J, and Bruns DK (1994) Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice. J Clin Investig 93:1885-1893.
13. 2b by probucol partly explains the failure of the drug to affect femoral atherosclerosis in subjects with hypercholesterolemia. A Probucol Quantitative Regression Swedish Trial (PQRST) Report. Arterioscler Thromb Vasc Biol 15:1049-1056.
14. Kaneko M, Hayashi J, Saito I, and Miyasaka N (1996) Probucol down-regulates E-selectin expression on cultured human vascular endothelial cells. Arterioscler Thromb Vasc Biol 16:1047-1051.
15. Keaney JF (2000) Antioxidants and vascular disease: animal studies, in Antioxidants and Cardiovascular Disease (Tardiff JC and Bourassa MG ed) pp 101-116, Kluwer Academic Publishers, Norwell, MA.
16. Klein L (1981) QTc-interval prolongation produced by probucol. Arch Intern Med 141:1102-1103.
17. Kleinveld HA, Demacker PN, and Stalenhoef AF (1994) Comparitive study on the effect of low-dose vitamin E and probucol on the susceptibility of LDL to oxidation and the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits. Arterioscler Thromb 14:1386-1391.
18. Kowala MC, Reece R, Beyer S, Gu C, and Valentine M (2000) Characterization of atherosclerosis in LDL receptor knockout mice: macrophage accumulation correlates with rapid and sustained expression of MCP-1/JE. Atherosclerosis 149:323-330.
19. Kunsch C and Medford RM (1999) Oxidative stress as a regulator of gene expression in the vasculature. Circ Res 85:753-766.
20. Marui N, Offermann MK, Swerlick R, Kunsch C, Rosen CA, Ahmad M, Alexander RW, and Medford RM (1993) Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant sensitive mechanism in human vascular endothelial cells. J Clin Investig 92:1866-1874.
21. Medford RM (1995) Antioxidants and endothelial expression of VCAM-1: A molecular paradigm for atherosclerosis. Cardiovascular Disease (Gallo LL) 2nd ed, pp 121-127, Plenum Press, NY.
22. Meng CQ, Somers PK, Rachita CL, Holt LA, Hoong LK, Zheng XS, Simpson JE, Hill RR, Olliff LK, Kunsch C, et al. (2002) Novel phenolic antioxidants as multifunctional inhibitors of inducible VCAM-1 expression for use in atherosclerosis. Bioorg Med Chem Lett 12:2545-2548.
23. Moghadasian MH, McManus BM, Godin DV, Rodrigues R, and Frohlich JJ (1999) Proatherogenic and antiatherogenic effects of probucol and phytosterols in apolipoprotein E-deficient mice: possible mechanisms of action. Circulation 99:1733-1739.
24. Palinski W, Horkko S, Miller E, Steinbrecher UP, Powell HC, Curtiss LK, and Witztum JL (1996) Cloning of monoclonal autoantibodies to epitopes of oxidized lipoproteins from apolipoprotein E-deficient mice. Demonstration of epitopes of oxidized low density lipoprotein in human plasma. J Clin Investig 98:800-814.
25. Parthasarathy S, Young SG, Witztum JL, Pittman RC, and Steinberg D (1986) Probucol inhibits oxidative modification of low density lipoprotein. J Clin Investig 77:641-644.
26. Ping D, Boekhoudt GH, Rogers EM, and Boss JM (1999) Nuclear factor-κB p65 mediates the assembly and activation of the TNF-responsive element of the murine monocyte chemoattractant protein-1 gene. J Immunol 162:727-734.
27. Ross R (1999) Atherosclerosis - an inflammatory disease. N Engl J Med 340:115-126.
28. Sasahara M, Raines EW, Chait A, Carew TE, Steinberg D, Wahl PW, and Ross R (1994) Inhibition of hypercholesterolemia-induced atherosclerosis in the nonhuman primate by probucol. J Clin Investig 94:155-164.
29. Sawayama Y, Shimizu C, Maeda N, Tatsukawa M, Kinukawa N, Koyanagi N, Koyanagi S, Kashiwagi S, and Hayashi J (2002) Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia. Fukuoka Atherosclerosis Trial (FAST). J Am Coll Card 39:610-616.
30. Tanaka K, Hayashi K, Shingu T, Kugu Y, Nomura K, and Kajiyama G (1998) Probucol inhibits neointimal formation in carotid arteries of normocholesterolemic rabbits and the proliferation of cultured rabbit vascular smooth muscle cells. J Cardiovasc Drugs Ther 12:19-28.
31. Tardif JC, Gregoire J, Schwartz L, Title L, Laramee L, Reeves F, Lesperance J, Bourassa MG, L'Allier PL, Glass M, et al. (2003) Effects of AGI-1067 and probucol after percutanecus coronary interventions. Circulation 107:552-558.
32. Weber C, Erl W, Pietsch A, Strobel M, Zeigler-Heitbrock HWL, and Weber PC (1994) Antioxidants inhibit monocyte adhesion by suppressing nuclear factor-κB mobilization and induction of vascular cell adhesion molecu]e-1 in endothelial cells stimulated to generate radicals. Arterioscler Thromb Vasc Biol 14:1665-1673.
33. Wissler RW and Vesselinovitch D (1983) Combined effects of cholestyramine and probucol on regression of atherosclerosis in Rhesus monkey aortas. Appl Pathol 1:89-96.
34. Witztum JL (1994) The oxidation hypothesis of atherosclerosis. Lancet 344:793-795.
35. Zapolska-Downer D, Zapolski-Downer A, Markiewski M, Ciechanowicz A, Kaczmarczyk M, and Naruszewicz M (2001) Selective inhibition by probucol of vascular cell adhesion molecule-1 (VCAM-1) expression in human vascular endothelial cells. Atherosclerosis 155:123-130.
36. Zhang SH, Reddick RL, Avdievich E, Surles KL, Jones RG, and Reynolds JB (1997) Paradoxical enhancement of atherosclerosis by probucol treatment in apolipoprotein E-deficient mice. J Clin Investig 99:2858-2866.
37. Zhang SH, Reddick RL, Piedrahita JA, and Maeda N (1992) Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science (Wash DC) 258:468-471.