Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
권호 표지
DOI QR코드

DOI QR Code

Pharmacophore Design for Anti-inflammatory Agent Targeting Interleukin-2 Inducible Tyrosine Kinase (Itk)

  • Chandrasekaran, Meganathan (Division of Applied Life Science(BK21 Program), Environmental Biotechnology National Core research Center (EB-NCRC), Plant Molecular Biology and Biotechnology Research Center(PMBBRC), Gyeongsang National University) ;
  • Sakkiah, Sugunadevi (Division of Applied Life Science(BK21 Program), Environmental Biotechnology National Core research Center (EB-NCRC), Plant Molecular Biology and Biotechnology Research Center(PMBBRC), Gyeongsang National University) ;
  • Thangapandian, Sundarapandian (Division of Applied Life Science(BK21 Program), Environmental Biotechnology National Core research Center (EB-NCRC), Plant Molecular Biology and Biotechnology Research Center(PMBBRC), Gyeongsang National University) ;
  • Namadevan, Sundaraganesan (Department of Physics (FEAT), Annamalai University) ;
  • Kim, Hyong-Ha (Division of Quality of Life, Korea Research Institute of Standards and Science) ;
  • Kim, Yong-Seong (Department of Science Education, Kyungnam University) ;
  • Lee, Keun-Woo (Division of Applied Life Science(BK21 Program), Environmental Biotechnology National Core research Center (EB-NCRC), Plant Molecular Biology and Biotechnology Research Center(PMBBRC), Gyeongsang National University)
  • Received : 2010.05.25
  • Accepted : 2010.09.15
  • Published : 2010.11.20
Download PDF
⟨ Previous Next ⟩

Abstract

A three dimensional pharmacophore model was generated for the molecules which are responsible for anti-inflammatory activities targeting Interleukin-2 inducible tyrosine kinase (Itk). 16 structurally diverse molecules were selected as training set to generate the hypotheses using Discovery Studio v2.1. The best hypothesis, Hypo1, comprises two hydrogen bond acceptor (HBA), one hydrophobic aromatic (HA), one ring aromatic (RA) and shows high cost difference (63.71), high correlation coefficient (0.97) as well as low RMS deviation (0.81). Hypo1 has been further validated toward a test set, decoy set and Fischer's randomization method. Furthermore, Hypo1 was used to screen NCI and Maybridge databases. Finally, 2 hit molecules were identified as potential leads against Itk, which may be useful for future drug development.

Keywords

References

  1. Merck Manual Home Edition.
  2. Merck Manual Professional Edition.
  3. Smith, C. I. E.; Islam, T. C.; Mattsson, P. T.; Mohamed, A. J.; Nore, B. F.; Vihinen, M. BioEssays 2009, 23, 436. https://doi.org/10.1002/bies.1062
  4. Das, J.; Liu, C.; Moquin, R. V.; Lin, J.; Furch, J. A.; Spergel, S. H.; McIntyre, K. W.; Shuster, D. J.; O’Day, K. D.; Penhallow, B.; Chen-Yi Hung.; Kanner, S. B.; Lin, T. A.; Dodd, J. H.; Barrish, J. C.; Wityak, J. Bioorg. Med. Chem. Lett. 2006, 16, 2411. https://doi.org/10.1016/j.bmcl.2006.01.115
  5. Snow, R. J.; Abeywardane, A.; Campbell, S.; Lord, J.; Kashem, M. A.; Khine, H. H.; King, J.; Kowalski, J. A.; Pullen, S. S.; Roma, T.; Roth, G. P.; Sarko, C. R.; Wilson, N. S.; Winters, M. P.; Wolak, J. P.; Cywin, C. L. Bioorg. Med. Chem. Lett. 2007, 17, 3660. https://doi.org/10.1016/j.bmcl.2007.04.045
  6. Kawakami, Y.; Kitaura, J.; Hata, D.; Yao, L.; Kawakami, T. J. Leukoc. Biol. 1999, 65, 286.
  7. Liao, X. C.; Littman, D. R. Immunity 1995, 3,757. https://doi.org/10.1016/1074-7613(95)90065-9
  8. Forssell, J.; Sideras, P.; Eriksson, C.; Malm-Erjefalt, M.; Rydell-Tormanen, K.; Ericsson, P. O.; Erjefalt, J. S. Am. J. Respir. Cell Mol. Biol. 2005, 32, 511. https://doi.org/10.1165/rcmb.2004-0348OC
  9. Acharya, B. N.; Kaushik, M. P. Med. Chem. Res. 2007, 16, 213. https://doi.org/10.1007/s00044-007-9025-8
  10. Cook, B. N.; Bentzien, J.; White, A.; Nemoto, P. A.; Wang, J.; Man, C. C.; Soleymanzadeh, F.; Khine, H. H.; Kashem, M. A.; Kugler S. Z., Jr.; Wolak, J. P.; Roth, G. P.; De Lombaert, S.; Pullen, S. S.; Takahashi, H. Bioorg. Med. Chem. Lett. 2009, 19, 773. https://doi.org/10.1016/j.bmcl.2008.12.028
  11. Moriarty, K. J.; Takahashi, H.; Pullen, S. S.; Khine, H. H.; Sallati, R. H.; Raymond, E. L.; Woska, J. R., Jr.; Jeanfavre, D. D.; Roth, G. P.; Winters, M. P.; Qiao, L.; Ryan, D.; Jarlais, R. D.; Robinson, D.; Wilson, M.; Bobko, M.; Cook, B. N.; Yin Lo, H.; Nemoto, P. A.; Kashem, M. A.; Wolak, J. P.; White, A.; Magolda, R. L.; Tomczuk, B. Bioorg. Med. Chem. Lett. 2008, 18, 5545. https://doi.org/10.1016/j.bmcl.2008.09.015
  12. Yin Lo, H.; Bentzien, J.; White, A.; Man, C. C.; Fleck, R. W.; Pullen, S. S.; Khine, H. H.; King, J.; Woska, J. R., Jr.; Wolak, J. P.; Kashem, M. A.; Roth, G. P.; Takahashi, H. Tetrahedron Lett. 2008, 49, 7337. https://doi.org/10.1016/j.tetlet.2008.10.057
  13. Das, J.; Furch, J. A.; Liu, C.; Moquin, R. V.; Lin, J.; Spergel, S. H.; McIntyre, K. W.; Shuster, D. J.; O’Day, K. D.; Penhallow, B.; Chen-Yi Hung.; Doweyko, A. M.; Kamath, A.; Zhang, H.; Marathe, P.; Kanner, S. B.; Tai-An Lin.; Dodd, J. H.; Barrish, J. C.; Wityak, J. Bioorg. Med. Chem. Lett. 2006, 16, 3706. https://doi.org/10.1016/j.bmcl.2006.04.060
  14. Yin Lo, H.; Bentzien, J; Fleck, R. W.; Pullen, S. S.; Khine, H. H.; Woska, J. R., Jr.; Kugler, S. Z.; Kashem, M. A.; Takahashi, H. Bioorg. Med. Chem. Lett. 2008, 18, 6218. https://doi.org/10.1016/j.bmcl.2008.09.098
  15. Lipinski, C. A. J. Pharmacol. Toxicol. Methods 2000, 44, 235. https://doi.org/10.1016/S1056-8719(00)00107-6
  16. Lu, I. L.; Tsai, K. C.; Chiang, Y. K.; Jiang, W. T.; Wu, S. H.; Mahindroo, N.; Chien, C. H.; Lee, S. J.; Chen, X.; Chao, Y. S.; Wu, S. Y. Eur. J. Med. Chem. 2008, 43, 1603. https://doi.org/10.1016/j.ejmech.2007.11.014
  17. Developmental Therapeutics Program, NCI/NIH, 2000, http://dtp.nci.nih.gov
  18. Maybridge Chemical company (England); http://www.chem.ac.ru/Chemistry/Databases/MAYBRIDGE.en.html.
  19. Li, H. F.; Lu, T.; Zhu, T.; Jiang, Y. J.; Rao, S. S.; Hu, L. Y.; Xin, B. T. E. J. Med. Chem. 2009, 44, 1240. https://doi.org/10.1016/j.ejmech.2008.09.016
  20. Venkatachalam, C. M.; Jiang, X.; Oldfield, T.; Waldman, M. J. Mol. Graph. Model. 2003, 21, 289. https://doi.org/10.1016/S1093-3263(02)00164-X
  21. Gehlhaar, D. K.; Verkhivker, G. M.; Rejto, P. A.; Sherman, C. J.; Fogel, D. R.; Fogel, L. J.; Freer, S. T. Chem. & Biol. 1995, 2, 317. https://doi.org/10.1016/1074-5521(95)90050-0
  22. Jain, A. N. J. Comput. Aid. Mol. Des. 1996, 10, 427. https://doi.org/10.1007/BF00124474
  23. Muegge, I.; Martin, Y. C. J. Med. Chem. 1999, 42, 791. https://doi.org/10.1021/jm980536j
  24. Bohm, H. J. J. Comput. Aid. Mol. Des. 1994, 8, 243. https://doi.org/10.1007/BF00126743
  25. Bohm, H. J. J. Comput. Aid. Mol. Des. 1998, 12, 309. https://doi.org/10.1023/A:1007999920146
  26. Debnath, A. K. J. Med. Chem. 2002, 45, 41. https://doi.org/10.1021/jm010360c
  27. Sakkiah, S.; krishnamoorthy, N.; Gajendraro, P.; Thangapandian, S.; Lee, Y.; Suh, J.; Kim, H. H.; Lee, K. W. Bull. Korean Chem. Soc. 2009, 30, 1152. https://doi.org/10.5012/bkcs.2009.30.5.1152
  28. Lee, Y.; Bharatham, N.; Bharatham, K.; Lee, K. W. Bull. Korean. Chem. Soc. 2007, 28, 561. https://doi.org/10.5012/bkcs.2007.28.4.561
  29. Fischer, R. A. The Design of Experiments; Hafner Publishing: New York, 1966 (Chapter 2).
  30. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Adv. Drug Delivery Rev. 2001, 46, 3. https://doi.org/10.1016/S0169-409X(00)00129-0
  31. Brown, K.; Long, J. M.; Vial, S. C. M.; Dedi, N.; Dunster, N. J.; Renwick, S. B.; Tanner, A. J.; Dan Frantz, J.; Fleming, M. A.; Cheetham, G. M. T. J. Biol. Chem. 2004, 279, 18727. https://doi.org/10.1074/jbc.M400031200

Cited by

  1. Macromolecular Docking Simulation to Identify Binding Site of FGB1 for Antifungal Compounds vol.32, pp.10, 2011, https://doi.org/10.5012/bkcs.2011.32.10.3675
  2. Discovery of potent inhibitors for interleukin-2-inducible T-cell kinase: structure-based virtual screening and molecular dynamics simulation approaches vol.19, pp.2, 2013, https://doi.org/10.1007/s00894-012-1536-7
  3. Combiphore (Structure and Ligand Based Pharmacophore) - Approach for the Design of GPR40 Modulators in the Management of Diabetes vol.17, pp.2, 2010, https://doi.org/10.2174/1570163815666181008165822