Sudabeh Shokrollahi - Department of Chemistry, College of Science, University of Tehran, Tehran, Iran
Ahmad Amiri - Department of Chemistry, College of Science, University of Tehran, Tehran, Iran
Aria Tajalli - Department of Chemistry, College of Science, University of Tehran, Tehran, Iran

Fibroblast activation protein (FAP) is a well-defined marker, expressed at high levels on the cell surface ofcancer associated fibroblasts (CAFs). FAP, a constitutively active serine peptidase with both dipeptidylpeptidase IV (DPP IV) and collagenase/gelatinase activity, promotes malignant and invasive behavior ofepithelial cancers. High stromal expression levels of FAP correlate with poor prognosis. FAP is difficult todetect in non-diseased adult tissue, but it is generally expressed at sites of tissue remodeling. Several potentialFAP-targeted approaches consisting of vaccines, antibodies, prodrugs, and inhibitors have been exploited inpreclinical studies. Among them, a class of FAP inhibitors (FAPi) with a N-(۴-quinolinoyl)-Gly-(۲-cyanopyrrolidine) scaffold displayed nanomolar affinity and high selectivity against other interferingdipeptidyl peptidases and prolyl oligopeptidase. In this study, several positron emission tomography (PET)tracers including FAPI-۰۲, FAPI-۰۴, FAPI-۴۶, and FAP-۲۲۸۶ were investigated. Quantum chemicalcalculations of these compounds have been carried out by DFT at the B۳LYP/۶–۳۱۱++G(d,p) level. Ananalysis of the calculated vibrational frequencies was performed and significant bands were specified.Furthermore, the binding affinity between the above-mentioned inhibitors and FAP was studied undersimulated physiological conditions, using molecular docking (MD). The results show that the FAP-۲۲۸۶compound has more affinity for binding to FAP.

FAP; DFT; Molecular Docking; CAFs; PET