Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 118, Issue 10, Pages 3462-3471Publisher
WILEY
DOI: 10.1002/jcb.26004
Keywords
LUNG CANCER; ALK; CRIZOTINIB; PERSONALIZED MEDICINE; MOLECULAR DOCKING; MOLECULAR DYNAMICS SIMULATION
Categories
Funding
- Science and Engineering Research Board-Department of Science and Technology, India [PDF/2015/000060]
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Anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients are mostly treated with ALK tyrosine kinase inhibitors (TKIs). Crizotinib is the first generation ALK inhibitor practiced as a primary chemo to combat cancer cells followed by second generation inhibitor ceritinib which are effective against crizotinib resistant ALK mutations. However, patients treated with these drugs invariably relapsed because of the development of new drug resistance mutations. In this study we explored the crizotinib resistance in the presence of ALK mutations L1196M and G1269A through molecular dynamics simulation studies. Further mutation specific inhibitors CID 71748211 and CID 71728095 were identified to potentially inhibit ALK with mutations L1196M and G1269A, respectively. This computational investigation in-sighted the molecular factors involved in crizotinib resistance which enhanced in the identification of new ALK drugs that brings individualized medicine to treat ALK positive NSCLC patients with specific mutations. (C) 2017 Wiley Periodicals, Inc.
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