Identifying potent inhibitors against GSK-3β for Non- Small Cell Lung Carcinoma: Molecular modelling approach, ADME/ pharmacokinetics profiling and statistical significance

Abstract

Glycogen synthase Kinase-3 beta (GSK-3β) has been reported as an important drug target in an array of human diseases including cancer due to its diverse role in numerous signaling pathways.GSK-3β regulates the WNT/β catenin signaling pathway which in response activates the genes which are regulated by T-cell factor/Lymphoid enhancer factor involved in tumorigenesis and malignancy. The phosphorylated GSK-3β Serine 9 is engaged with histogenesis of various non-small cell lung carcinomas (NSCLCs) as compared to small cell lung cancer. In this study, to check the activity of inhibitor against GSK 3β for non- small cell lung cancer, we have selected thirty-three compounds against carboplatin as a reference which shows good anticancer and antidiabetic properties. These compounds were utilized for the molecular docking by using Autodock 4 and further subjected to ADME/pharmacokinetics analysis. The results of study showed that the molecules with ZINC id- 3874496, 3875687, 7996283, 73683137, 2563085, 1306071, 21011059, have the best docking scores and ADME profile. Thus, these compounds can serve as an excellent candidate for drug development against GSK-3β in NSCLC patients. This study investigates the binding of druglike molecules to GSK-3β and has reported that residue Arg141 may be targeted for therapy in NSCLC patients. Further, statistical analysis (T- test) demonstrates that results are highly significant.