Discovery of potential ALK inhibitors by virtual screening approach.
Crizotinib is an anticancer drug used for the treatment of non-small cell lung cancer. Evidences available suggest that there is a development of an acquired resistance against crizotinib action due to the emergence of several mutations in the ALK gene. It is therefore necessary to develop potent anti-cancer drugs for the treatment of crizotinib resistance non-small cell lung cancer types. In the present study, a novel class of lead molecule was identified using virtual screening, molecular docking and molecular dynamic approach. The virtual screening analysis was done using PubChem database by employing crizotinib as query and the data reduction was carried out by using molecular docking techniques. The bioavailability of the lead compounds was examined with the help of Lipinski rule of five. The screened lead molecules were analyzed for toxicity profiles, drug-likeness and other physico-chemical properties of drugs by OSIRIS program. Finally, molecular dynamics simulation was also performed to validate the binding property of the lead compound. Our analysis clearly indicates that CID 11562217, a nitrile containing compound (pyrazole-substituted aminoheteroaryl), could be the potential ALK inhibitor certainly helpful to overcome the drug resistance in non-small cell lung cancer.
Industrial Biotechnology Division, School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu, 632014, India.
Anish
A
Kumar
Industrial Biotechnology Division, School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu, 632014, India.
V
V
Shanthi
Industrial Biotechnology Division, School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu, 632014, India. kramanathan@vit.ac.in.
K
K
Ramanathan
Crizotinib; Molecular docking; Molecular dynamic simulation; Mutation; Non-small cell lung cancer; Virtual screening