Song_2022_Chem.Biol.Interact__109830

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 potencial 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.