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exact role still remains unclear [13,24,25]. In the present work,
beta-nitrostyrenes potently inhibited the kinase activities and
tyrosine phosphorylation of Src and Syk, and this effect
paralleled their ability to inhibit platelet aggregation and
activation, suggesting that Src and Syk are the major targets of
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blockade of both Src and Syk may provide more effective
suppression of platelet aggregation than blockade of either
kinase alone. This suggestion is based on two observations.
First, compound 10 strongly inhibited in vitro activity of both
Src and Syk and exhibited greater antiplatelet effect than MNS
which preferentially inhibited the in vitro activity of Syk over
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nitrostyrene derivatives as tyrosine kinase inhibitors and
antiplatelet agents. Our results show that b-nitrostyrene
derivatives inhibited human platelet aggregation, ATP secre-
tion, GPIIb/IIIa activation and protein tyrosine phosphoryla-
tion. Furthermore, there was a good correlation between the
inhibitory potency of these derivatives on protein tyrosine
kinases and on platelet aggregation. Among these com-
pounds, a benzoyl ester derivative (compound 10) exhibited
greater activity than MNS, genistein, and tyrphostin A47.
Therefore, b-nitrostyrenes may represent a new class of
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which should serve as useful tools to investigate protein
tyrosine kinase and may have therapeutic potential for
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