Nv-52: a novel thromboxane synthase inhibitor for the treatment of inflammatory bowel disease

Abstract

NV-52, a synthetic flavonoid derivative, is a selective thromboxane synthase (TXS) inhibitor that is being developed as a treatment for inflammatory bowel disease. NV-52 selectively inhibits TXS in vitro in physiological relevant concentrations, causing a reduction in thromboxane B(2) of </= 40% in association with an increase in prostaglandin E(2). NV-52 is effective in suppressing colonic inflammation in a murine model of inflammatory bowel disease. NV-52 has not demonstrated any toxicity in in vitro and animal toxicological studies, and has been administered to normal volunteers in a Phase I clinical trial without detectable adverse effects. NV-52 is well absorbed and a single dose of 400 mg p.o. produced a plasma concentration that is comparable with the concentrations that have been shown to produce significant TXS inhibition in vitro.