In silico Analysis of Liriodenine as a Novel ATP-Competitive PIM 1 Inhibitor in some Cancer Cell-Lines of Haematopoietic and Prostate Origins

PIM1–an oncogenic kinase–is overexpressed in a number of haematopoietic malignancies as well as solid tumors such as prostate cancer where it correlates with poor prognosis. Several studies have elucidated the roles of PIM1 in cell-cycle progression, cell survival, and tumourigenesis. Also, the distinctive characteristics of the ATP binding pocket of this kinase have been vividly reported. Thus, PIM1 is an attractive target for the design of selective pharmacological inhibitors. In silico methods were executed to investigate the non-ATP mimetic properties of liriodenine in comparison with the co-crystallized 9G5 and CX-4945, which are potent ATP-competitive PIM inhibitors. Consequently, the outcome of our study depicted the interactions of liriodenine with catalytic important aminoacyl residues in the ATP binding site of PIM1. Considering the ADME and cytotoxic parameters of the screened drug-like candidates together with CX-4945, we also showed that liriodenine displayed an improved probable ATP-competitive PIM1 inhibition when compared to CX-4945, a drug currently in Phase I/II clinical trials against cholangiocarcinoma. In the light of these findings, we put forward a valid argument, indicating that liriodenine can be preclinically/clinically researched as a potential targeted cancer therapy for haematopoietic malignancies as well as other solid tumours, most especially in prostate cancer.