Inhibitors of JAKs/STATs and the kinases: a possible new cluster of drugs.

JAK(s)/STAT(s) relay cytokine signals through tyrosine site-specific phosphorylation of the proteins involved in cellular responses for the activation and proliferation of bone marrow-derived cells. In recent years, the constitutive or elevated expression of JAK/STAT has been found in cancer cells and oncogene transfected cells, and has been shown to be involved in the immune rejection of allografts and the inflammatory processes of autoimmune diseases. This review discusses the strategies for screening and rational design of selective, potent JAK/STAT and kinase inhibitors that are either ATP-competitive or non-ATP competitive, naturally derived or synthetic, as well as other unique inhibitors and analogues for different therapeutic indications.