WIPO Re:Search Database

E3040 as dual 5-lipoxygenase and thromboxane A2 synthetase inhibitor 
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.

E4177: Selective Angiotensin II inhibitor 
E4177 is an Angiotensin II antagonist which selectively inhibits AT1 receptor.

E5700 as squalene synthase inhibitor 
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.

E2011: Monoamine Oxidase A selective inhibitor 
E2011, a MAO-A inhibitor which has been developed for treament of depression, inhibits MAO-A selectively 30,000 times more than MAO-B in rat brain homogenate. E2011 is effective in animal (mice) at a dose of 0.3mg/kg p.o..

E4021 as type V phosphodiesterase (PDE) inhibitor 
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 F2, 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.

E4010 as phosphodiesterase type V inhibitor 
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.

TCAMS (Tres Cantos Antimalarial Set) 
Activity against P. falciparum

Tres Cantos Open Lab 
The open laboratory at GSK's Tres Cantos Medicines Development campus in Spain is designed to stimulate research into new treatments for diseases of the developing world. The open lab has space for visiting scientists from universities, not-for-profit partnerships and other research institutes to come to the site, work on projects with us, learn from our expertise and share our world-class facilities. We have set up a not-for-profit foundation with an initial investment of GBP 5 million to support visiting scientists and their research projects (the Tres Cantos Open Lab Foundation). A governing board of leading scientists within the field is providing strategic direction for the foundation and the research it supports. All projects supported by the Open Lab Foundation must contribute to research that helps discover new medicines for diseases of the developing world. The projects involve collaboration between the scientists home laboratory and GSK at Tres Cantos.

E5510: Inhibitor of platelet agregation 
E5510 inhibits platelet aggregation through inhibition of Prostaglandin H synthases and Phosphodiesterase.

A Novel Treatment for Malarial Infections 
The inventions include antimalarial small molecule inhibitors of the plasmodial surface anion channel (PSAC), an essential nutrient acquisition ion channel expressed on human erythrocytes infected with malaria parasites. These inhibitors were discovered by high-throughput screening of chemical libraries and analysis of their ability to kill malaria parasites in culture. Two separate classes of inhibitors were found to work synergistically in combination against PSAC and killed malaria cultures at markedly lower concentrations than separately. These inhibitors have high affinity and specificity for PSAC and have acceptable cytotoxicity profiles. Preliminary in vivo testing of these compounds in a mouse malaria model is ongoing.