A number of cytokines have been demonstrated to play a role in the development of inflammation. One of the most prominent of these, Tumor Necrosis Factor-alpha (TNF-alpha), has been found to be an important mediator of the pathophysiological effects of a diverse array of invasive diseases, infections, and inflammatory states. As a consequence of its production (or overproduction) in tissues, and the presence of other cytokines in the cellular environment, TNF-alpha may ultimately benefit or injure the host.

Based on the use of a unique screening system utilizing normal human cells, a series of compounds have been identified which are reasonably selective inhibitors of TNF-alpha or its related cytokine family members. These compounds have been shown to inhibit the production of their target cytokine without affecting the expression of a variety of other cytokines, adhesion molecules, or effector molecules including IL-1, IL-1ra, IL-2, IL-8, IL-10, TNFR-I, TNFR-II, PGE2, superoxide anion, or nitric oxide.

Unlike both marketed TNF-alpha antagonists and several new molecules under development, LeukoMed's proprietary compounds inhibit the synthesis of TNF-alpha within the cell so that it is never expressed, either on the cell surface or into the surrounding environment of the cell. This difference in mode of action, inhibition of synthesis versus capture of secreted TNF-alpha, is an important distinction: several studies have suggested that TNF-alpha on the surface of cells can still be biologically active. LeukoMed's compounds have been shown to inhibit TNF-alpha at one of the earliest stages of its synthesis. The small molecule nature of LeukoMed's compounds should provide much greater pharmacological control than can be achieved with protein-based antagonists.