title: Fluorescent Kinase Probes Enabling Identification and Dynamic Imaging of HER2(+) Cells.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Miami , Coral Gables, Florida 33146, United States.
authors.forename: Heajin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Miami , Miami, Florida 33101, United States.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Chemistry, University of Miami , Coral Gables, Florida 33146, United States.
authors.forename: Adrienne S
authors.initials: AS
authors.lastname: Brown
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Miami , Miami, Florida 33101, United States.
authors.forename: Ralf
authors.initials: R
authors.lastname: Landgraf
authors.affiliation: Department of Chemistry, University of Miami , Coral Gables, Florida 33146, United States.
authors.forename: James N
authors.initials: JN
authors.lastname: Wilson
mesh_terms: D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D009369:Neoplasms / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human