title: Inhibition of T lymphocyte activation by a novel p56lck tyrosine kinase inhibitor.
abstract: A new p56lck tyrosine kinase inhibitor WIN 61651 [1,4-dihydro-7-(4-methyl-1-piperizinyl)-1-(4-(4-methyl-1-piperi zinyl))phenyl- 4-oxo-3-quinolinecarboxamide) is described. WIN 61651, which is competitive with ATP, demonstrates selectivity for the lymphoid restricted tyrosine kinase p56lck over serine/threonine kinases, such as protein kinase C and protein kinase A, and over some other tyrosine kinases, including erbB2, epidermal growth factor receptor, and insulin receptor; however, it is equipotent for inhibition of p56lck and the platelet derived growth factor receptor tyrosine kinases. WIN 61651 inhibits p56lck activity in cell-free assays, tyrosine kinase activity in a T lymphocytic cell line, and T cell activation, as measured by IL-2 production by purified CD4 positive peripheral blood T lymphocytes and the mixed lymphocyte reaction. WIN 61651 constitutes a new tool for studies on the role for tyrosine kinases in lymphocyte function.
authors.affiliation: Department of Immunology, Sterling Winthrop Pharmaceuticals Research Division, Collegeville, PA 19426, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Faltynek
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Miller
authors.forename: P
authors.initials: P
authors.lastname: Mauvais
authors.forename: B
authors.initials: B
authors.lastname: Gauvin
authors.forename: J
authors.initials: J
authors.lastname: Reid
authors.forename: W
authors.initials: W
authors.lastname: Xie
authors.forename: S
authors.initials: S
authors.lastname: Hoekstra
authors.forename: P
authors.initials: P
authors.lastname: Juniewicz
authors.forename: J
authors.initials: J
authors.lastname: Sarup
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000906:Antibodies; D017252:CD3 Complex; D015704:CD4 Antigens; D004791:Enzyme Inhibitors; D010879:Piperazines; D011804:Quinolines; C098117:WIN 61651; D014443:Tyrosine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases