0599989 - ÚOCHB 2025 RIV NL eng J - Journal Article
Čermáková, Kateřina - Šimková, Adéla - Wichterle, Filip - Kryštůfek, Robin - Staňurová, Jana - Vaníčková, Z. - Bušek, P. - Konvalinka, Jan - Šácha, Pavel
Sensitive quantification of fibroblast activation protein and high-throughput screening for inhibition by FDA-approved compounds.
European Journal of Medicinal Chemistry. Roč. 280, December (2024), č. článku 116948. ISSN 0223-5234. E-ISSN 1768-3254
R&D Projects: GA MZd(CZ) NU22-03-00318; GA ČR(CZ) GA24-10814S; GA MŠMT LX22NPO5102; GA MŠMT(CZ) LM2023053
Institutional support: RVO:61388963
Keywords : DIANA * fibroblast activation protein * high-throughput screening * FAP quantification
Impact factor: 6, year: 2023 ; AIS: 0.978, rok: 2023
Method of publishing: Open access
Result website:
https://doi.org/10.1016/j.ejmech.2024.116948DOI: https://doi.org/10.1016/j.ejmech.2024.116948

Fibroblast activation protein (FAP) has been extensively studied as a cancer biomarker for decades. Recently, small-molecule FAP inhibitors have been widely adopted as a targeting moiety of experimental theranostic radiotracers. Here we present a fast qPCR-based analytical method allowing FAP inhibition screening in a high-throughput regime. To identify clinically relevant compounds that might interfere with FAP-targeted approaches, we focused on a library of FDA-approved drugs. Using the DNA-linked Inhibitor Antibody Assay (DIANA), we tested a library of 2667 compounds within just a few hours and identified numerous FDA-approved drugs as novel FAP inhibitors. Among these, prodrugs of cephalosporin antibiotics and reverse transcriptase inhibitors, along with one elastase inhibitor, were the most potent FAP inhibitors in our dataset. In addition, by employing FAP DIANA in the quantification mode, we were able to determine FAP concentrations in human plasma samples. Together, our work expands the repertoire of FAP inhibitors, analyzes the potential interference of co-administered drugs with FAP-targeting strategies, and presents a sensitive and low-consumption ELISA alternative for FAP quantification with a detection limit of 50pg/ml.
Permanent Link: https://hdl.handle.net/11104/0357358