E4010 selectively and potently inhibited PDE5 isolated from porcine platelet. E4010 markedly reduced the increased pulmonary arterial pressure with a slight effect on systemic arterial pressure in the porcine model of heart failure. Thus, E4010 would be useful for the treatment of patients with pulmonary hypertension.
E4021 is selective type V PDE inhibitor. E4021 caused a significant and sustained increase in the cGMP level in endothelium-denuded porcine coronary artery without effecting the cAMP level. E4021 had a relaxant effect in porcine coronary artery precontracted by prostaglandin F2Ã¯ÂÂ¡, in the absence of endothelial cells and relaxed it more markedly in the presence of endothelial cells. E4021 caused a dose-dependent dilation of the large epicardial coronary artery, with a reduction in mean pulmonary arterial pressure, in conscious pigs instrumented chronically with a pair of piezoelectric crystals. E4021 causes relaxation of the large coronary artery via an increase in the cGMP level.
Through the exploratory research for treatment of hypolipidemia, E5700 was found to be a novel squalene synthase inhibitor, E5700 possesses potent squalene synthase inhibitory activity and shows inhibitory activity to hepatic cholesterol biosynthesis in rats. It is also reported that E5700 possesses some activities against Leishmania amazonensis, Toxoplasma gondii tachyzoites, and Trypanosoma cruzi.
E3040 were found in the course of developing anti-inflammatory drug candidates for the treatment of inflammatory bowel diseases. E30340 inhibits both 5-lipoxygenase and TXA2 synthetase in cell-free in vitro assay. E3040 also showed therapeutic effect in TNB/ethanol-induced chronic colitis model by oral administration.