RESUMO
T-cells play an important role in the pathogenesis of many diseases. These include diseases with large commercial markets and also with significant unmet medical needs, such as rheumatoid arthritis and asthma in addition to those with smaller markets such as organ transplantation, multiple sclerosis, inflammatory bowel diseases, type 1 diabetes, systemic lupus erythematosus and psoriasis. The use of currently available immunomodulatory agents is often limited by the appearance of dose-limiting side effects that result from the actions of these agents on non-lymphoid tissues. LSTRA cell kinase (lck), one of eight known members of the human src family of non-transmembrane protein tyrosine kinases, has a pivotal role in T-cell signaling. Lck expression is restricted to lymphoid cells, so an lck-selective inhibitor would be expected to have a significantly improved safety profile for the treatment of T-cell-driven diseases.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/antagonistas & inibidores , Animais , Humanos , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/fisiologiaRESUMO
Pyrrolo[2,3-d]pyrimidines containing a 5-(4-phenoxyphenyl) substituent are potent and selective inhibitors of Ick in vitro; some compounds are selective for lck over src. Data are shown for two compounds demonstrating that they are potent and selective inhibitors of IL2 production in cells.