Abstract
Identification of activating mutations in non-small cell lung cancers (NSCLC) has been a focus in recent years. This led to successful
evidence of using tyrosine kinase inhibitors (TKIs) over the standard platinum doublet based chemotherapy as the first line
treatment in the metastatic setting.The rearrangements of fusion protein EML4-ALK in NSCLC lead to the use of crizotinib for this
class of tumors. Preclinical and Phase 1 clinical studies show that ceritinib is more effective against both crizotinib sensitive and
resistant tumors. Although robust responses to crizotinib are observed in NSCLC harboring ALK mutations, majority of tumors
eventually become resistant, posing a major challenge in treatment course. Thus, there is a need for the identification and
development of second-generation of ALK inhibitors. Computer aided molecular docking data show Tivozanib and Lapatinib bind
EML4-ALK with high score. Tivozanib is in clinical trials for renal cell cancer and Lapatinib is a known dual tyrosine kinase
inhibitor effective in breast cancer patients with HER2 over-expression. Additional data on these compounds for use in EML4-ALK
positive NSCLC will provide evidence for use in patients treated with crizotinib. Data shows the importance of computer aided
molecular docking in developing candidates with improved activity for further consideration in vitro and in vivo validation.