Fibroblast activation protein alpha: Comprehensive detection methods for drug target and tumor marker

Fibroblast activation protein alpha (FAP-alpha, EC3.4.2. B28), a type II transmembrane proteolytic enzyme for the serine protease peptidase family. It is underexpressed in normal tissues but increased significantly in disease states, especially in neoplasm, which is a potential biomarker to turmor diagnosis. The inhibition of FAP-alpha activity will retard tumor formation, which is expected to be a promising tumor therapeutic target. At present, although the FAP-alpha expression detection methods has diversification, a superlative detection means is necessary for the clinical diagnosis. This review covers the discovery and the latest advances in FAP-alpha, as well as the future research prospects. The tissue distribution, structural characteristics, small-molecule ligands and structure activity relationship of major inhibitors of FAP-alpha were summarized in this review. Furthermore, a variety of detection methods including traditional detection methods and emerging probes detection were classified and compared, and the design strategy and kinetic parameters of these FAP-alpha probe substrates were summarized. In addition, these comprehensive information provides a series of practical and reliable assays for the optimal design principles of FAP-alpha probes, promoting the application of FAP-alpha as a disease marker in diagnosis, and a drug target in drug design.

Automated summary

FAP-alpha is an enzyme associated with tumors, which is underexpressed in normal tissues but significantly increased in diseased states. This review provides an overview of the discovery and latest advances in FAP-alpha, including its structural characteristics, inhibitors, and detection methods.