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lüll Intracellular signal pathways: potential for therapies Mavers M; Ruderman EM; Perlman HCurr Rheumatol Rep 2009[Oct]; 11 (5): 378-85Drawbacks to current therapies for rheumatoid arthritis and the high cost of many of these drugs have lead to the investigation of novel approaches for treatment of this disease. One such tactic is the targeting of proteins involved in intracellular signal transduction. Inhibitors of p38 kinase have largely failed in clinical trials, due to both lack of efficacy and adverse events. The degree of adverse events may reflect off-target effects or, conversely, may be a mechanism-related event subsequent to successful inhibition of p38. Drugs targeting Janus kinases or spleen tyrosine kinase have shown greater success in clinical trials. A thorough analysis of specificity, as well as publication of both positive and negative results, must be the goal of continuing trials of these and other inhibitors of signal transduction molecules. The success of many clinical trials in this novel class of drugs provides optimism that more cost-effective and improved therapies will soon be available.|*Drug Delivery Systems[MESH]|*Drug Design[MESH]|Antirheumatic Agents/*therapeutic use[MESH]|Arthritis, Rheumatoid/*drug therapy/immunology[MESH]|Enzyme Inhibitors/therapeutic use[MESH]|Humans[MESH]|Mitogen-Activated Protein Kinases/antagonists & inhibitors/drug effects[MESH]|Signal Transduction/*drug effects[MESH] |