High impact information on Octimibate

• Therefore, the poor coupling of the IP receptor in SK-N-SH cells to G(q) is unlikely to explain the relatively low efficacy of octimibate for stimulating adenylyl cyclase in these cells [1].
• Since octimibate shows extensive species variation and is potent at inhibiting platelet aggregation in primates, all of the experiments reported here have been carried out with primate tissue or in vivo in cynomolgus monkeys [2].
• In platelet-rich plasma, octimibate inhibits agonist-stimulated aggregation with an IC50 of approx. 200 nM [3].
• Octimibate stimulates adenylyl cyclase activity in human platelet membranes, with an EC50 of 200 nM [3].
• Octimibate, a potent non-prostanoid inhibitor of platelet aggregation, acts via the prostacyclin receptor [3].

Biological context of Octimibate

• Octimibate inhibited ADP- and collagen-induced platelet aggregation in human, rabbit and rat platelet-rich plasma [4].
• When whole platelets were incubated with radiolabeled phosphate, octimibate produced an increase in the phosphorylation of platelet proteins with relative molecular weights of 22, 26, 50 and 80 kilodaltons [4].
• Prostacyclin agonists reduce early atherosclerosis in hyperlipidemic hamsters. Octimibate and BMY 42393 suppress monocyte chemotaxis, macrophage cholesteryl ester accumulation, scavenger receptor activity, and tumor necrosis factor production [5].

Anatomical context of Octimibate

• When isolated platelet plasma membranes were treated with octimibate, adenylate cyclase activity was stimulated, reaching maximal activation at 1 microM octimibate [4].
• Octimibate appears to be a partial agonist for relaxation of human coronary artery precontracted with KCl; the intrinsic activity of octimibate (10 microM) is 0.15 compared to iloprost, and octimibate surmountably antagonizes the relaxant effects of iloprost with a Kp of 200 nM [2].
• Cicaprost, iloprost, BMY 22389 (octimibate), BMY 42393 and BMY 45778 inhibited N-formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated neutrophil aggregation with IC50 values of 2.1, 4.5, 286, 462 and 20 nM, respectively [6].
• At 10 microM, octimibate and BMY 42393 decreased cholesteryl ester accumulation in macrophages by 90% and 41%, respectively [5].
• The in vitro results with octimibate and BMY 42393 are consistent with the low number of small foam cells quantified in vivo [5].

Associations of Octimibate with other chemical compounds

• Effects of octimibate, an inhibitor of acyl coenzyme A: cholesterol acyltransferase, on cholesterol metabolism in the hamster and rat [7].

Gene context of Octimibate

• Primate vascular responses to octimibate, a non-prostanoid agonist at the prostacyclin receptor [2].
• Since octimibate is a putative inhibitor of acyl coenzyme A cholesterol acyltransferase, we studied the effect of both agents on cholesteryl ester metabolism in murine macrophages [5].

References