Exploring the potential intracellular targets of vascular normalization based on active candidates.

As a continuation to our previous research, we preliminarily identified VEGFR-2 as potential intracellular targets of active candidates with the potency of inducing vascular normalization. • Discovery and functional assessment of novel photoaffinity probes were performed. • VEGFR-2 was identified as a potential intracellular target for active candidates. • These probes could be used for subcellular localization of target proteins. We previously developed two candidates with potency of inducing vascular normalization, BD7 and B14. However, the definite intracellular molecular target(s) responsible for their activity remains unknown. Herein, we report the discovery and functional assessment of several multifunctional photoaffinity probes for determining the potential biological targets of active compounds. The probes bear a photoaffinity moiety and a bioorthogonal unit attached to B7 or B14 and maintained the bioactivity of the parent active molecules. Using in vitro biological assays, we preliminarily identified VEGFR-2 as a potential intracellular target for the active candidates. Our results demonstrate the utility of these multifunctional photoaffinity probes for analyzing the biological activity and subcellular localization of the intracellular target proteins of active candidates. [ABSTRACT FROM AUTHOR]