Lck inhibitors as a therapeutic approach to autoimmune disease and transplant rejection.
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.
Kamens
J S
JS
Abbott Bioresearch Center, 100 Research Drive, Worcester, MA 01605, USA. joanne.niewood@abbott.com
Ratnofsky
S E
SE
Hirst
G C
GC
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology
D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)