Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) as a pathogenetically significant drug target for oncology therapy (molecular docking of irinotecan and doxycycline)

Abstract

Context. In recent years, overexpression and accumulation of heterogeneous nuclear ribonculoprotein A2B1 (hnRNPA2B1) in neoplasms has been considered as a new typical reaction on cancer progression. Therefore, hnRNPA2B1 is a pathogenetically significant target for antitumor drugs.

The aim of our study was the theoretical modeling in silico of the interactions of the anti-cancer drug irinotecan and the tetracycline antibiotic doxycycline with the hnRNPA2B1 protein.

Results. The affinity of doxycycline and irinotecan to hnRNP A2B1 was calculated by molecular docking method. According to the results, affinity of irinotecan (ΔG = –10.36 kcal/mol) is higher than the affinity of doxycycline (ΔG = –8.20 kcal/mol). However, the value of the binding energy of doxycycline indicates the formation of the hnRNPA2B1 – doxycycline complex, which makes further studies of doxycycline as an anticancer drug potentially interesting.

Conclusion. The binding energies (ΔG) of irinotecan and doxycycline to the target RNA-binding protein hnRNPA2B1 obtained by molecular modeling were -10.36 kcal/mol and -8.20 kcal/mol respectively. The calculated binding energy values indicate the pharmacologically significant formation of hnRNPA2B1–irinotecan and hnRNPA2B1–doxycycline complexes, which indicates another anti-cancer pleotropic effect of these drugs.