1st International and 10th National Iranian Conference on Bioinformatics
Home Accepted Papers
In-Silico Study of Fibroblast Activation Protein Binding of Recent FDA Approved Inhibitors
Paper ID : 1394-ICB10
Authors:
sudabeh سودابه shokrollahi *, احمد امیری1, آریا تجلی2
1شیمی معدنی- دانشکده شیمی- دانشگاه تهران
2دانشکده شیمی دانشگاه تهران
Abstract:
Fibroblast activation protein (FAP) is a well-defined marker, expressed at high levels on the cell surface of cancer associated fibroblasts (CAFs) [1]. FAP, a constitutively active serine peptidase with both dipeptidyl peptidase IV (DPP IV) and collagenase/gelatinase activity, promotes malignant and invasive behavior of epithelial cancers. High stromal expression levels of FAP correlate with poor prognosis. FAP is difficult to detect in non-diseased adult tissue, but it is generally expressed at sites of tissue remodeling [2]. Several potential FAP-targeted approaches consisting of vaccines, antibodies, prodrugs, and inhibitors have been exploited in preclinical studies [3]. Among them, a class of FAP inhibitors (FAPi) with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold displayed nanomolar affinity and high selectivity against other interfering dipeptidyl peptidases and prolyl oligopeptidase [4]. In this study, several positron emission tomography (PET) tracers including FAPI-02, FAPI-04, FAPI-46, and FAP-2286 were investigated. Quantum chemical calculations of these compounds have been carried out by DFT at the B3LYP/6–311++G(d,p) level. An analysis 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 under simulated physiological conditions, using molecular docking (MD). The results show that the FAP-2286 compound has more affinity for binding to FAP.
Keywords:
FAP; DFT; Molecular Docking; CAFs; PET.
Status : Paper Accepted (Poster Presentation)