REVIEWSmall molecules in the treatment of systemic lupus erythematosus

Advances in the understanding of the cellular biological events that underlie systemic lupus erythematosus (SLE) have led to the identification of key molecules and signaling pathways that are aberrantly expressed. The parallel development of small molecule drugs that inhibit or interfere with the specific perturbations identified, offers perspective for more rational, effective and less toxic therapy. In this review, we present data from preclinical and clinical studies of such emerging novel therapies with a particular focus on kinase inhibitors and other compounds that modulate signal transduction. Moreover, we highlight the use of chromatin-modifying medications, bringing attention to the central role of epigenetics in SLE pathogenesis.

► Inhibition of Syk normalizes the aberrant SLE T cell phenotype. ► mTOR inhibition with rapamycin was effective in an open label trial in SLE patients. ► Dipyridamole represents a non-toxic alternative to cyclosporine and tacrolimus. ► Epigenetic changes in chromatin structure represent a novel target for SLE therapy.