Back to Search
Start Over
Synthesis and photophysical properties of a fluorescent cyanoquinoline probe for profiling ERBB2 kinase inhibitor response.
- Source :
-
Bioorganic & Medicinal Chemistry . Nov2017, Vol. 25 Issue 21, p6016-6023. 8p. - Publication Year :
- 2017
-
Abstract
- A fluorescent probe targeting the ERBB2 receptor tyrosine was designed, synthesized and evaluated as reporter of ERBB2 dynamics in overexpressing BT474, i.e. Her2(+), cells. Two cyanoquinazoline ( CQ ) probes modeled after type-I ( CQ1 ) or active state and type-II ( CQ2 ) or inactive state inhibitors were designed and synthesized with extended π systems that impart binding-induced, turn-on fluorescence. Solution spectroscopy revealed that CQ1 exhibited attractive photophysical properties and displayed turn-on emission in the presence of purified, soluble ERBB2 kinase domain, while CQ2 was found to be non-emissive, likely due to quenching via a photoinduced electron transfer mechanism. Live cell imaging with CQ1 revealed that this probe targeted an intracellular population of ERBB2, which increased following treatment with type-I inhibitors, gefinitib and canertinib, but showed no response to type-II inhibitors. CQ1 thus provides a novel means of imaging the dynamic response of ERBB2(+) cells to kinase inhibitors. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TYROSINE
*CELL imaging
*CHARGE exchange
*FLUORESCENCE
*PHARMACEUTICAL chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 09680896
- Volume :
- 25
- Issue :
- 21
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 125859794
- Full Text :
- https://doi.org/10.1016/j.bmc.2017.09.034