Crizotinib is an anticancer drug used for the treatment of non-small cell lung cancer (NSCLC). The available evidence suggests that there is development of resistance against crizotinib action due to the emergence of mutations in anaplastic lymphoma kinase (ALK) gene. It is therefore necessary to develop potent anti-cancer drugs for the treatment of crizotinib resistance NSCLC. In the present study, a novel class of lead molecule was screened from plant sources using molecular simulation approach. The bioavailability of the lead compounds was examined with the help of Lipinski rule of five. The toxicity profiles and other physico-chemical properties of drugs were analyzed by OSIRIS program. Additionally, docking strategy was employed to examine the ALK inhibitory activities of the compounds considered in our study. Finally, molecular dynamics simulations were also performed to validate the binding property of the lead compound against native and mutant ALK proteins. Our analysis clearly indicates that CID 9848024 (neoandrographolide) could be the potential ALK inhibitor certainly helpful to overcome the drug resistance in NSCLC. Additionally, the results highlight the importance of traditional plant based compound in the control of drug resistance pattern in cancer. © 2016, Scientific Publishers of India. All rights reserved.