PT  - JOURNAL ARTICLE
AU  - OHKURA, KAZUTO
AU  - TABATA, ATSUSHI
AU  - UTO, YOSHIHIRO
TI  - Interactive Analysis of UTX-114 Family With EGFR-tyk: Molecular Features of Acetyl Glycosylated Gefitinib
AID  - 10.21873/anticanres.17181
DP  - 2024 Aug 01
TA  - Anticancer Research
PG  - 3587--3591
VI  - 44
IP  - 8
4099  - http://ar.iiarjournals.org/content/44/8/3587.short
4100  - http://ar.iiarjournals.org/content/44/8/3587.full
SO  - Anticancer Res2024 Aug 01; 44
AB  - Background/Aim: Acetyl glucose adducts (UTX-114, -115, and -116) were prepared from gefitinib, and their characteristics (e.g., anticancer activity, structural property) were analyzed. Materials and Methods: Cytotoxicity and radiosensitizing properties of the UTX-114 family were examined using A431 cells. Supramolecular associations between the UTX-114 family compounds and the tyrosine kinase domain of epidermal growth factor receptor (EGFR-tyk) were also examined. The interactive analyses of the UTX-114 family compounds with EGFR-tyk were performed using docking simulation technique. Results: The UTX-114 family showed a similar cytotoxicity as gefitinib, yielding IC50 values of 31.2 μM (gefitinib), 34.3 μM (UTX-114), 36.8 μM (UTX-115), and 39.4 μM (UTX-116). The EGFR-tyk inhibition ratios (IR) of UTX-114, -115, and -116 to gefitinib were 1.515, 0.983, and 0.551, respectively. The EGFR-tyk inhibitory activity of UTX-114 was higher than that of gefitinib. UTX-114 also showed the highest radiosensitizing activity among the tested compounds. UTX-114 expressed 1841 conformers (−8.989~15.718 kcal/mol) with the solvation free energy (dGW) of UTX-114 decreasing with increasing conformational energy, ranging between −354.955~ −260.815 kJ/mol. Interactive energies of gefitinib, UTX-114, -115, and -116 with EGFR-tyk were −123.640, −144.053, −120.830, and −124.658 kcal/mol, respectively. Conclusion: UTX-114 yielded the lowest interaction energy with EGFR-tyk among tested compounds. Given the association behavior between UTX-114 and EGFR-tyk, along with its other observed properties, UTX-114 appears to be a viable therapeutic possibility.