AGI-1067, a novel vascular protectant, anti-inflammatory drug and mild antiplatelet agent for treatment of atherosclerosis.
Oxidation-sensitive signals play an important role in platelet activation. AGI-1067 is a novel, phenolic, intra- and extracellular antioxidant that inhibits the expression of a number of proinflammatory genes involved in atherosclerosis. AGI-1067 is the metabolically stable monosuccinic acid ester of probucol, and a potent phenolic antioxidant representing a novel class of orally bioavailable compounds termed vascular protectants. AGI-1067 exhibits antioxidant activity equipotent to probucol. In addition, animal studies have demonstrated dual pharmacological activities of AGI-1067: the ability to block the expression of oxidation-sensitive inflammatory genes including genes that code for vascular cell adhesion molecule-1 and monocyte chemotactic protein-1. Importantly, AGI-1067 also exhibits mild antiplatelet properties inhibiting surface expression of various key platelet receptors, the formation of platelet monocyte microparticles and PAR-1 thrombin receptors. AGI-1067 is currently being tested in the late trials, and if proven to improve clinical outcomes (ARISE trial), the drug will ultimately be used in patients with different manifestations of atherosclerosis and atherothrombosis.
Serebruany
Victor L
VL
HeartDrug Research Laboratories, Osler Medical Center, 7600 Osler Drive, Suite 307, Towson, MD 21204, USA. heartdrug@aol.com
Malinin
Alex
A
Eisert
Christian
C
Ong
Stephen
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D001792:Blood Platelets / Q000187:drug effects; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000517:prevention & control; D023903:Coronary Restenosis / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011341:Probucol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000975:Antioxidants; D016207:Cytokines; D000960:Hypolipidemic Agents; D010975:Platelet Aggregation Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C471047:succinobucol; D011341:Probucol