Cell- and Tissue-Based Proteome Profiling and Bioimaging with Probes Derived from a Potent AXL Kinase Inhibitor

Binbin Zheng; Haijun Guo; Nan Ma; Yun Ni; Jiaqian Xu; Lin Li; Piliang Hao; Ke Ding; Zhengqiu Li

doi:10.1002/asia.201800605

Cell- and Tissue-Based Proteome Profiling and Bioimaging with Probes Derived from a Potent AXL Kinase Inhibitor

Chem Asian J. 2018 Sep 17;13(18):2601-2605. doi: 10.1002/asia.201800605. Epub 2018 Aug 7.

Authors

Binbin Zheng¹, Haijun Guo¹, Nan Ma¹, Yun Ni², Jiaqian Xu¹, Lin Li², Piliang Hao³, Ke Ding¹, Zhengqiu Li¹

Affiliations

¹ School of Pharmacy, Jinan University, Guangzhou City Key Laboratory of Precision Chemical Drug Development, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development, Ministry of Education (MOE) of People's Republic of China, 601 Huangpu Avenue West, Guangzhou, 510632, China.
² Institute of Advanced Materials (IAM), Nanjing Tech University, China.
³ School of Life Science and Technology, ShanghaiTech University, China.

PMID: 29939481
DOI: 10.1002/asia.201800605

Abstract

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.

Keywords: AXL; imaging; probes; proteomics; target identification.

MeSH terms

Animals
Axl Receptor Tyrosine Kinase
Cell Line, Tumor
Click Chemistry
Fluorescence
Fluorescent Dyes / chemistry
Fluorescent Dyes / metabolism*
Fluorescent Dyes / radiation effects
Humans
Male
Mice, Inbred ICR
Microscopy, Fluorescence
Molecular Docking Simulation
Photoaffinity Labels / chemistry
Photoaffinity Labels / metabolism*
Photoaffinity Labels / radiation effects
Protein Binding
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / metabolism*
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / radiation effects
Proteome / chemistry
Proteome / metabolism*
Proto-Oncogene Proteins / antagonists & inhibitors*
Proto-Oncogene Proteins / chemistry
Quinolones / chemistry
Quinolones / metabolism*
Quinolones / pharmacology
Quinolones / radiation effects
Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
Receptor Protein-Tyrosine Kinases / chemistry
Ultraviolet Rays

Substances

Fluorescent Dyes
Photoaffinity Labels
Protein Kinase Inhibitors
Proteome
Proto-Oncogene Proteins
Quinolones
Receptor Protein-Tyrosine Kinases
Axl Receptor Tyrosine Kinase