Drug Design for ALK-Positive NSCLC: an Integrated Pharmacophore-Based 3D QSAR and Virtual Screening Strategy
The increasing death rates related to anaplastic lymphoma kinase (ALK)-positive lung cancer culminated in a significant interest in the discovery of novel inhibitors for ALK. In the present research work, pharmacophore-based 3D QSAR modeling and virtual screening strategy have been carried out to address these issues. Initially, a five-point pharmacophore model was developed using the biological data of 50 compounds which includes an FDA-approved ALK inhibitor, crizotinib. Using the generated pharmacophore, a 3D QSAR model was developed and used as a query to screen the DrugBank database. The model was found to be significant (R 2 = 0.9696) with an excellent predictive accuracy (Q 2 = 0.7652) as confirmed through validation of the both training and test molecule activities. Further, Glide docking score and absorption, distribution, metabolism and excretion properties were used to filter the screened candidates. Overall, our analysis results in three hits namely TR1, FAL, ZYW with higher docking scores, and good pharmaceutically relevant properties with increased CNS involvement. It is worth mentioning that FAL and ZYW were found to possess scaffolds with specific activity against ALK protein. We presume that the results obtained from this computational study are of immense importance in the rational designing of novel and more potent ALK inhibitors.
Publisher URL: https://link.springer.com/article/10.1007/s12010-017-2650-x
Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.
Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.