Table of Contents
Journal of Computational Medicine
Volume 2014, Article ID 563080, 12 pages
http://dx.doi.org/10.1155/2014/563080
Research Article

Combined 3D QSAR Based Virtual Screening and Molecular Docking Study of Some Selected PDK-1 Kinase Inhibitors

School of Biochemical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India

Received 30 September 2013; Revised 21 December 2013; Accepted 6 January 2014; Published 1 June 2014

Academic Editor: Jeon-Hor Chen

Copyright © 2014 Shalini Singh and Pradeep Srivastava. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. A. Fabian, W. H. Biggs III, D. K. Treiber et al., “A small molecule-kinase interaction map for clinical kinase inhibitors,” Nature Biotechnology, vol. 23, no. 3, pp. 329–336, 2005. View at Publisher · View at Google Scholar · View at Scopus
  2. G. Manning, D. B. Whyte, R. Martinez, T. Hunter, and S. Sudarsanam, “The protein kinase complement of the human genome,” Science, vol. 298, no. 5600, pp. 1912–1934, 2002. View at Publisher · View at Google Scholar · View at Scopus
  3. I. Akritopoulou-Zanze and P. J. Hajduk, “Kinase-targeted libraries: the design and synthesis of novel, potent, and selective kinase inhibitors,” Drug Discovery Today, vol. 14, no. 5-6, pp. 291–297, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. S. L. Anderson, D. Stokoe, H. Erdjument-Bromage et al., “Prohtein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B,” Science, vol. 279, no. 5351, pp. 710–714, 1998. View at Publisher · View at Google Scholar · View at Scopus
  5. D. R. Alessi, M. Deak, A. Casamayor et al., “3-Phosphoinositide-dependent protein kinase-1 (PDK-1): structural and functional homology with the Drosophila DSTPK61 kinase,” Current Biology, vol. 7, pp. 776–789, 1997. View at Google Scholar
  6. R. A. Currie, K. S. Walker, A. Gray et al., “Role of phosphatidylinositol 3,4,5-trisphosphate in regulating the activity and localization of 3-phosphoinositide-dependent protein kinase-1,” Biochemical Journal, vol. 337, no. 2-3, pp. 575–583, 1999. View at Google Scholar · View at Scopus
  7. T. Kobayashi and P. Cohen, “Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK-1) and PDK2,” Biochemical Journal, vol. 339, no. 2, pp. 319–328, 1999. View at Publisher · View at Google Scholar · View at Scopus
  8. T. Kobayashi, M. Deak, N. Morrice, and P. Cohen, “Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase,” Biochemical Journal, vol. 344, no. 1, pp. 189–197, 1999. View at Publisher · View at Google Scholar · View at Scopus
  9. J. Park, M. L. Leong, P. Buse, A. C. Maiyar, G. L. Firestone, and B. A. Hemmings, “Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway,” The EMBO Journal, vol. 18, no. 11, pp. 3024–3033, 1999. View at Publisher · View at Google Scholar · View at Scopus
  10. N. Pullen, P. B. Dennis, M. Andjelkovic et al., “Phosphorylation and activation of p70s6k by PDK-1,” Science, vol. 279, no. 5351, pp. 707–710, 1998. View at Publisher · View at Google Scholar · View at Scopus
  11. D. R. Alessi, M. T. Kozlowski, Q. P. Weng, N. Morrice, and J. Avruch, “3-phosphoinositide-dependent protein kinase 1 (PDK-1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro,” Current Biology, vol. 8, no. 2, pp. 69–81, 1998. View at Publisher · View at Google Scholar · View at Scopus
  12. A. Mora, D. Komander, D. M. F. van Aalten, and D. R. Alessi, “PDK-1, the master regulator of AGC kinase signal transduction,” Seminars in Cell and Developmental Biology, vol. 15, no. 2, pp. 161–170, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. P. L. Dahia, “PTEN, a unique tumor suppressor gene,” Endocrine-Related Cancer, vol. 7, no. 2, pp. 115–129, 2000. View at Google Scholar · View at Scopus
  14. I. Sansal and W. R. Sellers, “The biology and clinical relevance of the PTEN tumor suppressor pathway,” Journal of Clinical Oncology, vol. 22, no. 14, pp. 2954–2963, 2004. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Cully, H. You, A. J. Levine, and T. W. Mak, “Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis,” Nature Reviews Cancer, vol. 6, no. 3, pp. 184–192, 2006. View at Publisher · View at Google Scholar · View at Scopus
  16. Y. Kurogi and O. F. Guner, “Pharmacophore modeling and three-dimensional database searching for drug design using catalyst,” Current Medicinal Chemistry, vol. 8, no. 9, pp. 1035–1055, 2001. View at Google Scholar · View at Scopus
  17. O. F. Guner, O. Clement, and Y. Kurogi, “Pharmacophore modeling and three dimensional database searching for drug design using catalyst: recent advances,” Current Medicinal Chemistry, vol. 11, no. 22, pp. 2991–3005, 2004. View at Google Scholar · View at Scopus
  18. H. K. Kyung, W. Allan, B. F. J. Middleton et al., “Benzo[c][2,7]naphthyridines as inhibitors of PDK-1,” Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 17, pp. 5225–5228, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. N. Thomas, G. D. Russell, I. Charles et al., “The identification of 8,9-dimethoxy-5-(2-aminoalkoxy-pyridin-3-yl)-benzo[c][2,7]naphthyridin-4-ylamines as potent inhibitors of 3-phosphoinositide-dependent kinase-1 (PDK-1),” European Journal of Medicinal Chemistry, vol. 45, no. 4, pp. 1379–1386, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. J. Zhu, J.-W. Huang, P.-H. Tseng et al., “From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors,” Cancer Research, vol. 64, no. 12, pp. 4309–4318, 2004. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Gopalsamy, M. Shi, D. H. Boschelli et al., “Discovery of dibenzo[c,f][2,7]naphthyridines as potent and selective 3-phosphoinositide-dependent kinase-1 inhibitors,” Journal of Medicinal Chemistry, vol. 50, no. 23, pp. 5547–5549, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. Accelrys Discovery Studio 2. 5, Accelrys, San Diego, Calif, USA, 2009, http://www.accelrys.com/.
  23. A. Smellie, S. Teig, and P. Towbin, “Poling: promoting conformational variation,” Journal of Computational Chemistry, vol. 16, no. 2, pp. 171–187, 1995. View at Publisher · View at Google Scholar
  24. B. R. Brooks, R. E. Brucolleri, B. D. Olafson, D. J. States, S. Swaminathan, and M. Karplus, “CHARMM: a program for macromolecular energy, minimization, and dynamics calculations,” Journal of Computational Chemistry, vol. 4, no. 2, pp. 187–217, 1983. View at Publisher · View at Google Scholar
  25. H. Li, J. Sutter, and R. Hoffmann, Pharmacophore Perception and Development and Use in Drug Design, International University Line, La Jolla, Calif, USA, edited by O. F. Guner, 2000.
  26. J. R. Medina, C. W. Blackledge, D. A. Heerding et al., “Aminoindazole PDK-1 inhibitors: a case study in fragment-based drug discovery,” ACS Medicinal Chemistry Letters, vol. 1, no. 8, pp. 439–442, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. D. Komander, G. S. Kular, A. W. Schüttelkopf et al., “Interactions of LY333531 and other bisindolyl maleimide inhibitors with PDK-1,” Structure, vol. 12, no. 2, pp. 215–226, 2004. View at Publisher · View at Google Scholar · View at Scopus
  28. C. M. Venkatachalam, X. Jiang, T. Oldfield, and M. Waldman, “LigandFit: a novel method for the shape-directed rapid docking of ligands to protein active sites,” Journal of Molecular Graphics and Modelling, vol. 21, no. 4, pp. 289–307, 2003. View at Publisher · View at Google Scholar · View at Scopus