JTE-607 is a multiple cytokine inhibitor. JTE-607 inhibited inflammatory cytokine production, including tumour necrosis factor (TNF)-alpha, interleukin IL-1beta, IL-6, IL-8, and IL-10, from LPS-stimulated human PBMCs. This compound may be useful for the treatment of various cytokine-mediated diseases such as septic shock without causing immunosuppression. JTE-607 may thus be efficacious in cytokine-mediated lung inflammation such as acute respiratory distress syndrome. JTE-607 inhibits the production of IL-10, IL-1ra and C-reactive protein in a human model of endotoxemia. In a leukaemia model engrafted with U-937 cells, JTE-607 significantly prolonged survival in mice and reduced human cytokine mRNA levels in the bone marrow. These results suggest the usefulness of JTE-607 in therapeutic applications for patients with hypercytokinemia and aggressive acute myelogenous leukaemia cell proliferation. JTE-607 had been in phase II clinical trials for the treatment of systemic inflammatory response syndrome but this study was discontinued.

ABT-491 is highly potent, selective and orally active platelet-activating factor (PAF) receptor antagonist, developed by Abbott Laboratories for allergic rhinitis treatment. ABT-491 is a potent antagonist of responses linked to the PAF receptor at the cellular level, especially platelets and neutrophils. ABT-491 was also effective in blocking platelet activation in blood, indicating that the presence of high concentrations of protein and other serum factors slightly alters the ability of ABT-491 to interact with PAF receptor. ABT-491 effectively antagonizes PAF-induced platelet and neutrophil responses at submicromolar concentrations in vitro and exhibits in vivo efficacy in alleviating PAF-mediated inflammatory and pathological processes in various animals, including guinea pigs, mice, and rats, via either i.v., i.p. or p.o. routes.