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Pharmaceutical intervention in the JAK/STAT signaling pathway Seidel HM; Lamb P; Rosen JOncogene 2000[May]; 19 (21): 2645-56Many cytokines exert their effect via the JAK/STAT signal transduction pathway. Due to the medical relevance of many of these cytokines, they are being exploited, either directly, or through antagonists, as therapeutics for a variety of serious diseases. Currently, these therapeutics consist almost entirely of protein products, with all of their attendant drawbacks. Delineation of the signaling mechanisms for the cytokines, however, has allowed the design and implementation of a variety of cell-based and biochemical screens for small molecule mimics or antagonists of these cytokines. Several successful assays will be described along with the advantages of each type of assay. Use of assays of this type should make it possible to discover numerous small molecule cytokine modulators with significant utility in the clinic. Oncogene (2000).|*Drug Evaluation, Preclinical[MESH]|*Signal Transduction/drug effects[MESH]|Animals[MESH]|Cell Line[MESH]|Cytokines/antagonists & inhibitors/pharmacology[MESH]|DNA-Binding Proteins/*antagonists & inhibitors/metabolism[MESH]|Enzyme Activation/drug effects[MESH]|Enzyme Inhibitors/pharmacology[MESH]|Growth Substances/pharmacology[MESH]|Humans[MESH]|Janus Kinase 1[MESH]|Molecular Mimicry[MESH]|Protein Binding[MESH]|Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism[MESH]|STAT1 Transcription Factor[MESH]|Trans-Activators/*antagonists & inhibitors/metabolism[MESH] |
