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

ABSTRACT: 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.

SUBMITTER: Turetsky A

PROVIDER: S-EPMC3998017 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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

Turetsky Anna A Kim Eunha E Kohler Rainer H RH Miller Miles A MA Weissleder Ralph R

Scientific reports 20140424

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-b ...[more]

PMID: 24759210

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