Scientific reports 2014-01-01

Single cell imaging of Bruton's tyrosine kinase using an irreversible inhibitor.

Anna Turetsky, Eunha Kim, Rainer H Kohler, Miles A Miller, Ralph Weissleder

文献索引：Sci. Rep. 4 , 4782, (2014)

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摘要

A number of Bruton's tyrosine kinase (BTK) inhibitors are currently in development, yet it has been difficult to visualize BTK expression and pharmacological inhibition in vivo in real time. We synthesized a fluorescent, irreversible BTK binder based on the drug Ibrutinib and characterized its behavior in cells and in vivo. We show a 200 nM affinity of the imaging agent, high selectivity, and irreversible binding to its target following initial washout, resulting in surprisingly high target-to-background ratios. In vivo, the imaging agent rapidly distributed to BTK expressing tumor cells, but also to BTK-positive tumor-associated host cells.