Neuroblastoma is a tumour of the sympathetic nervous system mainly prevalent in children. Many strategies have been employed to target several
drug-targetable
proteins for the clinical management of
neuroblastoma. However, the heterogeneous nature of
neuroblastoma presents serious challenges in
drug development for its treatment. Albeit numerous medications have been developed to target various signalling pathways in
neuroblastoma, the redundant nature of the tumour pathways makes its suppression unsuccessful. Recently, the quest for
neuroblastoma therapy resulted in the identification of human ALYREF, a
nuclear protein that plays an essential role in tumour growth and progression. Therefore, this study used the structure-based
drug discovery method to identify the putative inhibitors targeting ALYREF for the
Neuroblastoma treatment. Herein, a library of 119 blood-brain barrier crossing small molecules from the ChEMBL database was downloaded and docked against the predicted binding pocket of the
human ALYREF protein. Based on docking scores, the top four compounds were considered for intermolecular interactions and molecular dynamics simulation analysis, which revealed CHEMBL3752986 and CHEMBL3753744 with substantial affinity and stability with the ALYREF. These results were further supported by binding free energies and essential dynamics analysis of the respective complexes. Hence, this study advocates the sorted compounds targeting ALYREF for further in vitro and in vivo assessment to develop a
drug against
neuroblastoma.Communicated by Ramaswamy H. Sarma.