Browse > Article
http://dx.doi.org/10.5012/bkcs.2010.31.11.3333

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)
Publication Information
Bulletin of the Korean Chemical Society / v.31, no.11, 2010 , pp. 3333-3340 More about this Journal
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
Itk; Pharmacophore modeling; Virtual screening; Docking; HypoGen;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
Times Cited By Web Of Science : 1  (Related Records In Web of Science)
Times Cited By SCOPUS : 2
연도 인용수 순위
1 Venkatachalam, C. M.; Jiang, X.; Oldfield, T.; Waldman, M. J. Mol. Graph. Model. 2003, 21, 289.   DOI   ScienceOn
2 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.   DOI   ScienceOn
3 Jain, A. N. J. Comput. Aid. Mol. Des. 1996, 10, 427.   DOI
4 Muegge, I.; Martin, Y. C. J. Med. Chem. 1999, 42, 791.   DOI   ScienceOn
5 Bohm, H. J. J. Comput. Aid. Mol. Des. 1994, 8, 243.   DOI
6 Bohm, H. J. J. Comput. Aid. Mol. Des. 1998, 12, 309.   DOI   ScienceOn
7 Debnath, A. K. J. Med. Chem. 2002, 45, 41.   DOI   ScienceOn
8 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.   과학기술학회마을   DOI   ScienceOn
9 Lee, Y.; Bharatham, N.; Bharatham, K.; Lee, K. W. Bull. Korean. Chem. Soc. 2007, 28, 561.   과학기술학회마을   DOI   ScienceOn
10 Fischer, R. A. The Design of Experiments; Hafner Publishing: New York, 1966 (Chapter 2).
11 Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Adv. Drug Delivery Rev. 2001, 46, 3.   DOI   ScienceOn
12 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.   DOI   ScienceOn
13 Acharya, B. N.; Kaushik, M. P. Med. Chem. Res. 2007, 16, 213.   DOI
14 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.   DOI   ScienceOn
15 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.   DOI   ScienceOn
16 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.   DOI   ScienceOn
17 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.   DOI   ScienceOn
18 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.   DOI   ScienceOn
19 Lipinski, C. A. J. Pharmacol. Toxicol. Methods 2000, 44, 235.   DOI   ScienceOn
20 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.   DOI   ScienceOn
21 Developmental Therapeutics Program, NCI/NIH, 2000, http://dtp.nci.nih.gov
22 Maybridge Chemical company (England); http://www.chem.ac.ru/Chemistry/Databases/MAYBRIDGE.en.html.
23 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.   DOI   ScienceOn
24 Merck Manual Home Edition.
25 Merck Manual Professional Edition.
26 Kawakami, Y.; Kitaura, J.; Hata, D.; Yao, L.; Kawakami, T. J. Leukoc. Biol. 1999, 65, 286.
27 Smith, C. I. E.; Islam, T. C.; Mattsson, P. T.; Mohamed, A. J.; Nore, B. F.; Vihinen, M. BioEssays 2009, 23, 436.   DOI   ScienceOn
28 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.   DOI   ScienceOn
29 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.   DOI   ScienceOn
30 Liao, X. C.; Littman, D. R. Immunity 1995, 3,757.   DOI   ScienceOn
31 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.   DOI   ScienceOn