Analysis of styryl-based inhibitors of the lymphocyte tyrosine protein kinase p56lck.
Several styryl-based compounds were evaluated for their capacity to act as inhibitors of the non-receptor tyrosine protein kinase p56lck. Our results demonstrate that alpha-cyanocinnamamide compounds can inhibit both the in vitro tyrosine autophosphorylation of p56lck as well as p56lck phosphorylation of exogenous substrates. Compound 67B-83-A was found to inhibit p56lck protein kinase activity with a calculated IC50 of 7 to 10 microM. This compound did not significantly inhibit the tyrosine protein kinase activity of the epidermal growth factor receptor and was found to be a less effective tyrosine protein kinase inhibitor for other members of the src family of protein kinases.
Li
Z H
ZH
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543.
Burke
T R
TR
Bolen
J B
JB
D000818:Animals; D002460:Cell Line; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D015448:Leukemia, B-Cell; D015459:Leukemia-Lymphoma, Adult T-Cell; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008214:Lymphocytes; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000494:pharmacology*
D013343:Styrenes; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)