CGS 15435

CGS 15435, a potent thromboxane (TxA₂) synthetase inhibitor with an IC₅₀ of 1 nM, has a selectivity for Tx synthetase 100000-fold greater than that for cyclooxygenase, PGI₂ synthetase and lipoxygenase enzymes. IC50 & Target: IC50: 1 nM (TxA₂ synthetase), 60 μM (5-Lipoxygenase), 90 μM (PGI₂ synthetase), 1200 μM (Cyclooxygenase)^[1] In Vitro: CGS 15435 is a highly specific Tx synthetase inhibitor. CGS 15435 is only weakly effective as an inhibitor of PGE₂ (Cyclooxygenase, IC₅₀=1200 μM), prostacyclin (PGI₂ synthetase, IC₅₀=90 μM) or 5-Lipoxygenase (IC₅₀=60 μM) product formation^[1]. In Vivo: CGS 15435 has a long duration of action, since the increases in the plasma levels of TxB₂ are prevented even at 24 h after CGS 15435 administration. CGS 15435 significantly inhibits TxB₂ formation 4, 6, 12 and 24 h after dosing. Administration of CGS 15435 0.25 or 24 h prior to Arachidonic acid (AA) produced no increase in TxB₂ in the surviving animals (4/4 and 5/6, respectively). The final TxB₂ levels in the CGS15435A (0.25 and 24 h pretreatment) groups are significantly lower (P<0.05) than those seen in the AA or the Dazoxiben (2 h pretreatment) groups^[1].