Optimized Near-IR Fluorescent Agents for in Vivo Imaging of Btk Expression

被引：49

作者：

Kim, Eunha ^{[1
]}

Yang, Katherine S. ^{[1
]}

Kohler, Rainer H. ^{[1
]}

Dubach, John M. ^{[1
]}

Mikula, Hannes ^{[1
]}

Weissleder, Ralph ^{[1
,2
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

来源：

BIOCONJUGATE CHEMISTRY | 2015年 / 26卷 / 08期

基金：

美国国家卫生研究院;

关键词：

BRUTONS-TYROSINE-KINASE; TARGETING BTK; SI-RHODAMINE; LIVE-CELL; IBRUTINIB; INHIBITOR; MACROPHAGES; ACTIVATION; PCI-32765; POTENT;

D O I：

10.1021/acs.bioconjchem.5b00152

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Bruton's tyrosine kinase (Btk) is intricately involved in anti-apoptotic signaling pathways in cancer and in regulating innate immune response. A number of Btk inhibitors are in development for use in treating B-cell malignancies and certain immunologic diseases. To develop robust companion imaging diagnostics for in vivo use, we set out to explore the effects of red wavelength fluorochrome modifications of two highly potent irreversible Btk inhibitors, Ibrutinib and AVL-292. Surprisingly, we found that subtle chemical differences in the fluorochrome had considerable effects on target localization. Based on iterative designs, we developed a single optimized version with superb in vivo imaging characteristics enabling single cell Btk imaging in vivo. This agent (Ibrutinib-SiR-COOH) is expected to be a valuable chemical tool in deciphering Btk biology in cancer and host cells in vivo.

引用

页码：1513 / 1518

页数：6

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