Cell- and Tissue-Based Proteome Profiling and Bioimaging with Probes Derived from a Potent AXL Kinase Inhibitor.
Binbin ZhengHaijun GuoNan MaYun NiJiaqian XuLin LiPiliang HaoKe DingZhengqiu LiPublished in: Chemistry, an Asian journal (2018)
AXL has been defined as a novel target for cancer therapeutics. However, only a few potent and selective inhibitors targeting AXL are available to date. Recently, our group has developed a lead compound, 9im, capable of displaying potent and specific inhibition of AXL. To further identify the cellular on/off targets, in this study, competitive affinity-based proteome profiling was carried out, leading to the discovery of several unknown cellular targets such as BCAP31, LPCAT3, POR, TM9SF3, SCCPDH and CANX. In addition, trans-cyclooctene (TCO) and acedan-containing probes were developed to image the binding between 9im and its target proteins inside live cells and tumor tissues. These probes would be useful tools in the detection of AXL in various biosystems.
Keyphrases
- tyrosine kinase
- small molecule
- living cells
- single cell
- fluorescence imaging
- single molecule
- induced apoptosis
- papillary thyroid
- gene expression
- fluorescent probe
- cell cycle arrest
- squamous cell carcinoma
- high throughput
- quantum dots
- deep learning
- mesenchymal stem cells
- mass spectrometry
- nucleic acid
- squamous cell
- transcription factor
- photodynamic therapy
- label free
- endoplasmic reticulum stress
- signaling pathway
- loop mediated isothermal amplification
- young adults
- sensitive detection
- lymph node metastasis
- pi k akt