Journal of Integrative Natural Science (통합자연과학논문집)

The Basic Science Institute Chosun University (조선대학교 기초과학연구원)
권호 표지
DOI QR코드

DOI QR Code

Identification of inhibitors against ROS1 targeting NSCLC by In- Silico approach

  • Bavya, Chandrasekhar (Department of Microbiology, School of Biological Science, CMS College of Science and Commerce)
  • Received : 2022.11.23
  • Accepted : 2022.12.23
  • Published : 2022.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

ROS1 (c-ros oncogene) is one of the gene with mutation in NSCLC (non-small cell lung cancer). The increased expression of ROS1 is leading to the increase proliferation of cell, cell migration and survival. Crizotinib and Entrectinib are the drugs that have been approved by FDA against ROS1 protein, but recently patients started to develop resistance against Crizotinib and there is a need of new drug that could act as an effective drug against ROS1 for NSCLC. In this study, we have performed virtual screening, where compounds are taken from Zinc 15 dataset and molecular docking was performed. The top compounds were taken based upon their binding affinity and their interactions with the residues. The compounds stability and chemical reactivity was also studied through Density Functional theory and their properties. Further study of these compounds could reveal the required information of ROS1-inhibitor complex and in the discovery of potent inhibitors.

Keywords

References

  1. Alice T. Shaw, Sai-Hong I. Ou, YungJue Bang, D. Ross Camidge, et al, "Crizotinib in ROSl-Rearranged NonSmall-Cell Lung Cancer", Vol. 371, pp. 1963-1971, 2014.
  2. Jessica J.Lin, Alice T.Shaw, "Recent Advances in Targeting ROS1 in Lung Cancer", Journal of Thoracic Oncology., Vol. 12, pp. 1611-1625, 2017. https://doi.org/10.1016/j.jtho.2017.08.002
  3. Justin F. Gainor, Alice T. Shaw, "Novel Targets in Non-Small Cell Lung Cancer: and Fusions", , Vol. 18, pp. 865-875, 2013.
  4. Robert Roskoski, " ROS1 Protein-Tyrosine Kinase Inhibitors in the Treatment of ros1 Fusion Protein-Driven Non-Small Cell Lung Cancers", Pharmacol Res., Vol.121, pp. 202-212, 2017. https://doi.org/10.1016/j.phrs.2017.04.022
  5. Davare M.A, Vellore N.A, Wagner J.P, Eide C.A, Goodman J.R, Drilon A, Deininger M.W, O'Hare T, Druker B.J, "Structural Insight Into Selectivity and Resistance Profiles of ROS1 Tyrosine Kinase Inhibitors", Proc. Natl. Acad. Sci. pp. 1-10, 215.
  6. Rikova K., Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, et al, "Global Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer", Cell., Vol. 131, pp.1190-1203, 2007. https://doi.org/10.1016/j.cell.2007.11.025
  7. Mazieres J, Zalcman G, Crino L, Biondani P, Barlesi F, Filleron T, Dingemans A.-M.C, Lena H, Monnet I, Rothschild S.I, et al, "Crizotinib Therapy for Advanced Lung Adenocarcinoma and a ROS1 Rearrangement: Results from the EUROS1 Cohort", J. Clin. Oncol., Vol. 33, pp.992- 999,2015. https://doi.org/10.1200/jco.2014.58.3302
  8. Gainor J.F, Shaw A.T., "Novel Targets in Non-Small Cell Lung Cancer:ROS1 and RET Fusions", Oncologist.,Vol. 18, pp. 865-875, 2013. https://doi.org/10.1634/theoncologist.2013-0095
  9. McCoach C.E, Le A.T, Gowan K, Jones K, Schubert L, Doak A, Estrada-Bernal A, Davies K.D, Merrick D.T, Bunn P.A, et al, "Resistance Mechanisms to Targeted Therapies in ROS1p and ALKp Non-Small Cell Lung Cancer", Clin Cancer Res., Vol. 24, pp . 3334-3347,2018. https://doi.org/10.1158/1078-0432.CCR-17-2452
  10. Drilon A, Somwar R, Wagner J.P, Vellore N.A, Eide C.A, Zabriskie M.S, Arcila M.E, Hechtman J.F, Wang L, Smith R.S, et al, "A Novel Crizotinib-Resistant Solvent-Front Mutation Responsive to Cabozantinib Therapy in a Patient with ROS1-R earranged Lung Cancer", Clin. Cancer Res., Vol. 22, pp. 2351-2358, 2016. https://doi.org/10.1158/1078-0432.CCR-15-2013
  11. Bergethon K, Shaw A.T, Ou S.-H.I, Katayama R, Lovly C.M, McDonald N.T, Massion P.P, Siwak-Tapp C, Gonzalez A, Fang R, et al, "ROS1 Rearrangements Define a Unique Molecular Class of Lung Cancers", J. Clin. Oncol., Vol. 30, pp. 863-870, 2012. https://doi.org/10.1200/JCO.2011.35.6345
  12. Dallakyan, S. and Olson, A.J, "Small-molecule library screening by docking with PyRx", In Chemical biology., pp. 243-250, 2015.
  13. Leach, A. R, Shoichet, B. K, &Peishoff, C. E, "Prediction of protein- ligand interactions. Docking and scoring: successes and gaps", Journal of medicinal chemistry., Vol. 49, pp. 5851-5855, 2006. https://doi.org/10.1021/jm060999m
  14. Trott, O, & Olson, A. J. "AutoDockVina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading", Journal of computational chemistry., Vol. 3 ,pp. 455-461, 2010.
  15. Parr RG, Yang W, "Density-functional theory of atoms and molecules", Oxford University Press, New York, 1989.
  16. Fukui, K., "The role of frontier orbitals in chemical reactions", (Nobel Lecture). AngewandteChemie International Edition in English, Vol. 21 pp. 801-809,1982. https://doi.org/10.1002/anie.198208013
  17. Chattaraj, P.K. and Roy, D.R, "Update 1 of: electrophilicity index", Chemical reviews., Vol. 107, pp. 46-74,2007.
  18. Chattaraj, P.K, Maiti, B. and Sarkar, U,"Philicity: a unified treatment of chemical reactivity and selectivity", The Journal of Physical Chemistry A, Vol. 107, pp. 4973-4975, 2003. https://doi.org/10.1021/jp034707u
  19. Chattaraj, P.K, Sarkar, U, Roy, D.R, Elango, M., Parthasarathi, R. and Subramanian, V, "Is electrophilicity a kinetic or a thermodynamic concept?", Vol 45A, pp. 1099-1112, 2006.
  20. Pires, D. E., Blundell, T. L., &Ascher, D. B., "pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures", Journal of medicinal chemistry., Vol. 58, pp. 4066-4072, 2015. https://doi.org/10.1021/acs.jmedchem.5b00104