TY - JOUR
T1 - Fluorescent kinase probes enabling identification and dynamic imaging of HER2(+) Cells
AU - Lee, Heajin
AU - Liu, Wenjun
AU - Brown, Adrienne S.
AU - Landgraf, Ralf
AU - Wilson, James N.
N1 - Funding Information:
This work was supported by the National Cancer Institute Innovative Molecular Analysis Technologies Program, CA182341-03 (J.N.W. and R.L.). J.N.W. also acknowledges seed funding from the American Cancer Society (98-277-07). R.L. also acknowledges the support of National Cancer Institute, CA98881-05, and the Braman Family Breast Cancer Institute.
Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/12/6
Y1 - 2016/12/6
N2 - The human epidermal growth factor receptor, EGFR/ ERBB/HER, family of receptor tyrosine kinases is central to many signaling pathways and a validated chemotherapy target in multiple cancers. While EGFR/ERBB-targeted therapies, including monoclonal antibodies, e.g., trastuzumab, and small molecule kinase inhibitors, such as lapatinib, have been developed, rapid identification and classification of cancer cells is key to identifying the best treatment regime. We report ERBB2 (also HER2) targeting kinase probes that exhibit a "turn-on" emission response upon binding. These live cell compatible probes differentiate ERBB2(+) cells from low-level, ERBB2(-) cells by targeting the intracellular ATP-binding pocket of ERBB2 with therapeutic inhibitor-like specificity. Beyond kinase expression levels, probe signal is linked to the phosphotyrosine-correlated activation state of the ERBB2 population. Additionally, the rapid signaling capability of the probes can report changes in activation state in live cells providing a unique type of complementary information to immunohistochemical assays of receptor kinase populations.
AB - The human epidermal growth factor receptor, EGFR/ ERBB/HER, family of receptor tyrosine kinases is central to many signaling pathways and a validated chemotherapy target in multiple cancers. While EGFR/ERBB-targeted therapies, including monoclonal antibodies, e.g., trastuzumab, and small molecule kinase inhibitors, such as lapatinib, have been developed, rapid identification and classification of cancer cells is key to identifying the best treatment regime. We report ERBB2 (also HER2) targeting kinase probes that exhibit a "turn-on" emission response upon binding. These live cell compatible probes differentiate ERBB2(+) cells from low-level, ERBB2(-) cells by targeting the intracellular ATP-binding pocket of ERBB2 with therapeutic inhibitor-like specificity. Beyond kinase expression levels, probe signal is linked to the phosphotyrosine-correlated activation state of the ERBB2 population. Additionally, the rapid signaling capability of the probes can report changes in activation state in live cells providing a unique type of complementary information to immunohistochemical assays of receptor kinase populations.
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U2 - 10.1021/acs.analchem.6b03836
DO - 10.1021/acs.analchem.6b03836
M3 - Article
C2 - 27934102
AN - SCOPUS:85032869937
VL - 88
SP - 11310
EP - 11313
JO - Analytical Chemistry
JF - Analytical Chemistry
SN - 0003-2700
IS - 23
ER -