The first pharmacophore model for potent NF-κB inhibitors

Keng-Chang Tsai, Li-Wei Teng, Yi-Ming Shao, Yu-Chen Chen, Yu-Ching Lee, Min-Yong Li, Nai-Wan Hsiao

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

As an important transcription factor of the Ral family, nuclear factor-kappa B (NF-κB) is involved in numerous cellular processes, such as the responses to cellular stress and to inflammation. For better elucidating the quantitative structure-activity relationship of NF-κB inhibitors and determining possible ligand-protein interaction, a pharmacophore model, Hypo1, was built based on 35 training molecules by Catalyst/HypoGen algorithm. The five pharmacophore features of Hypo1, including three hydrophobic groups, one hydrogen-bond acceptor, and one hydrophobic aromatic group, were correctly mapped onto NF-κB surface. This model has strong capability to identify NF-κB inhibitors and to predict the activities of structurally diverse molecules, thus to provide a valuable tool in the design of new leads with desired biological activity by virtual screening. © 2009 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)5665-5669
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number19
DOIs
Publication statusPublished - 2009
Externally publishedYes

Fingerprint

NF-kappa B
Molecules
Quantitative Structure-Activity Relationship
Bioactivity
Hydrogen
Hydrogen bonds
Screening
Transcription Factors
Ligands
Inflammation
Catalysts
Proteins

Keywords

  • catalyst
  • NF-κB inhibitor
  • Pharmacophore
  • QSAR
  • I kappa B
  • immunoglobulin enhancer binding protein
  • ligand
  • protein
  • article
  • hydrogen bond
  • hydrophobicity
  • pharmacophore
  • protein interaction
  • structure activity relation
  • Binding Sites
  • Combinatorial Chemistry Techniques
  • Computer Simulation
  • Ligands
  • Models, Chemical
  • NF-kappa B
  • Quantitative Structure-Activity Relationship
  • Software

Cite this

Tsai, K-C., Teng, L-W., Shao, Y-M., Chen, Y-C., Lee, Y-C., Li, M-Y., & Hsiao, N-W. (2009). The first pharmacophore model for potent NF-κB inhibitors. Bioorganic and Medicinal Chemistry Letters, 19(19), 5665-5669. https://doi.org/10.1016/j.bmcl.2009.08.021

The first pharmacophore model for potent NF-κB inhibitors. / Tsai, Keng-Chang; Teng, Li-Wei; Shao, Yi-Ming; Chen, Yu-Chen; Lee, Yu-Ching; Li, Min-Yong; Hsiao, Nai-Wan.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 19, No. 19, 2009, p. 5665-5669.

Research output: Contribution to journalArticle

Tsai, K-C, Teng, L-W, Shao, Y-M, Chen, Y-C, Lee, Y-C, Li, M-Y & Hsiao, N-W 2009, 'The first pharmacophore model for potent NF-κB inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 19, pp. 5665-5669. https://doi.org/10.1016/j.bmcl.2009.08.021
Tsai, Keng-Chang ; Teng, Li-Wei ; Shao, Yi-Ming ; Chen, Yu-Chen ; Lee, Yu-Ching ; Li, Min-Yong ; Hsiao, Nai-Wan. / The first pharmacophore model for potent NF-κB inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2009 ; Vol. 19, No. 19. pp. 5665-5669.
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abstract = "As an important transcription factor of the Ral family, nuclear factor-kappa B (NF-κB) is involved in numerous cellular processes, such as the responses to cellular stress and to inflammation. For better elucidating the quantitative structure-activity relationship of NF-κB inhibitors and determining possible ligand-protein interaction, a pharmacophore model, Hypo1, was built based on 35 training molecules by Catalyst/HypoGen algorithm. The five pharmacophore features of Hypo1, including three hydrophobic groups, one hydrogen-bond acceptor, and one hydrophobic aromatic group, were correctly mapped onto NF-κB surface. This model has strong capability to identify NF-κB inhibitors and to predict the activities of structurally diverse molecules, thus to provide a valuable tool in the design of new leads with desired biological activity by virtual screening. {\circledC} 2009 Elsevier Ltd. All rights reserved.",
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author = "Keng-Chang Tsai and Li-Wei Teng and Yi-Ming Shao and Yu-Chen Chen and Yu-Ching Lee and Min-Yong Li and Nai-Wan Hsiao",
note = "被引用次數:4 Export Date: 28 March 2016 CODEN: BMCLE 通訊地址: Hsiao, N.-W.; Institute of Biotechnology, National Changhua University of Education, Changhua, 50007, Taiwan; 電子郵件: nady@cc.ncue.edu.tw 化學物質/CAS: protein, 67254-75-5; Ligands; NF-kappa B 參考文獻: Sen, R., Baltimore, D., (1986) Cell, 46, p. 705; Beg, A.A., Baldwin Jr., A.S., (1993) Genes Dev., 7, p. 2064; Baeuerle, P.A., Henkel, T., (1994) Annu. Rev. Immunol., 12, p. 141; Verma, I.M., Stevenson, J.K., Schwarz, E.M., Van Antwerp, D., Miyamoto, S., (1995) Genes Dev., 9, p. 2723; Alkalay, I., Yaron, A., Hatzubai, A., Orian, A., Ciechanover, A., Ben-Neriah, Y., (1995) Proc. Natl. Acad. Sci. U.S.A., 92, p. 10599; Brown, K., Gerstberger, S., Carlson, L., Franzoso, G., Siebenlist, U., (1995) Science, 267, p. 1485; Scherer, D.C., Brockman, J.A., Chen, Z., Maniatis, T., Ballard, D.W., (1995) Proc. Natl. Acad. Sci. U.S.A., 92, p. 11259; Phelps, C.B., Sengchanthalangsy, L.L., Malek, S., Ghosh, G., (2000) J. Biol. Chem., 275, p. 24392; Berkowitz, B., Huang, D.B., Chen-Park, F.E., Sigler, P.B., Ghosh, G., (2002) J. Biol. Chem., 277, p. 24694; Schwartz, M.D., Moore, E.E., Moore, F.A., Shenkar, R., Moine, P., Haenel, J.B., Abraham, E., (1996) Crit. Care Med., 24, p. 1285; Gilston, V.J., Jones, H.W., Soo, C.C., Coumbe, A., Blades, S., Kaltschmidt, C., Baeuerle, P.A., Winyard, P.G., (1997) Biochem. Soc. Trans., 25, pp. 518S; Keates, S., Hitti, Y.S., Upton, M., Kelly, C.P., (1997) Gastroenterology, 113, p. 1099; Finco, T.S., Baldwin, A.S., (1995) Immunity, 3, p. 263; Baldwin Jr., A.S., (1996) Annu. Rev. Immunol., 14, p. 649; Barnes, P.J., Karin, M., (1997) N. Eng. J. Med., 336, p. 1066; Fiedler, M.A., Wernke-Dollries, K., Stark, J.M., (1998) Am. J. Respir. Cell Mol. Biol., 19, p. 259; Nunokawa, Y, Nakatsuka, T, Saitoh, M, Abe, K. World (PTC) Patent WO-0005234, 2000Tobe, M., Isobe, Y., Tomizawa, H., Nagasaki, T., Takahashi, H., Fukazawa, T., Hayashi, H., (2003) Bioorg. Med. Chem., 11, p. 383; Tobe, M., Isobe, Y., Tomizawa, H., Nagasaki, T., Takahashi, H., Hayashi, H., (2003) Bioorg. Med. Chem., 11, p. 3869; Li, H., Sutter, J., Hoffmann, R., (2000) Pharmacophore Preception, Development and Use in Drug Design, p. 171. , Guner, O. F, Ed, CA; http://www.accelrys.com, Catalyst. Version 4.11 software package, Accelry: San Diego, CA; 2005Debnath, A.K., (2002) J. Med. Chem., 45, p. 41; Du, L.P., Tsai, K.C., Li, M.Y., You, Q.D., Xia, L., (2004) Bioorg. Med. Chem. Lett., 14, p. 4771; Yang, Q., Du, L.P., Tsai, K.C., Wang, X.J., Li, M.Y., You, Q.D., (2009) QSAR Comb. Sci., 28, p. 59; Li, M.Y., Tsai, K.C., Xia, L., (2005) Bioorg. Med. Chem. Lett., 15, p. 657; Brooks, B.R., Bruccoleri, R.E., Olafson, B.D., States, D.J., Swaninathan, S., Karplus, M., (1983) J. Comput. Chem., 4, p. 187; Smellie, A., Teig, S.L., Tobwin, P., (1995) J. Comput. Chem., 16, p. 171; Sprague, P.W., (1995) Perspect. Drug Discovery Des., 3, p. 1; Baumann, B., Bohnenstengel, F., Siegmund, D., Wajant, H., Weber, C., Herr, I., Debatin, K.M., Wirth, T., (2002) J. Biol. Chem., 47, p. 44791; de-Blanco, E.J., Pandit, B., Hu, Z., Shi, J., Lewis, A., Li, P.K., (2007) Bioorg. Med. Chem. Lett., 17, p. 6031; Xie, Y.D.S., Thomas, C.J., Liu, Y., Zhang, Y.Q., Rinderspacher, A., Huang, W., Gong, G., Auld, D.S., (2008) Bioorg. Med. Chem. Lett., 18, p. 329; Muller, C.W., Rey, F.A., Sodeoka, M., Verdine, G.L., Harrison, S.C., (1995) Nature, 373, p. 311; Chen, F.E., Huang, D.B., Chen, Y.Q., Ghosh, G., (1998) Nature, 391, p. 410; Prasad, A.S., Bao, B., Beck, F.W., Sarkar, F.H., (2001) J. Lab Clin. Med., 138, p. 250; Pande, V., Sharma, R.K., Inoue, J., Otsuka, M., Ramos, M.J., (2003) J. Comput. Aided. Mol. Des., 17, p. 825; Sharma, R.K., Otsuka, M., Pande, V., Inoue, J., Jo{\~a}o Ramos, M., (2004) Bioorg Med Chem Lett., 14, p. 6123; Pante, V., Ramos, M.J., (2005) Bioorg. Med. Chem. Lett., 15, p. 4057; Piccagli, L.F.E., Borgatti, M., Bezzerri, V., Mancini, I., Nicolis, E., Dechecchi, M.C., Lampronti, I., Gambari, R., (2008) BMC Struct. Biol., 8, p. 38; gold is distributed by the Cambridge Crystallographic Data Center, Cambridge, UK, http://www.ccdc.ac.uk/prods/gold.htmlJones, G., Willett, P., Glen, R.C., (1995) J. Mol. Biol., 245, p. 43; Jones, G., Willett, P., Glen, R.C., Leach, A.R., Taylor, R., (1997) J. Mol. Biol., 267, p. 727",
year = "2009",
doi = "10.1016/j.bmcl.2009.08.021",
language = "English",
volume = "19",
pages = "5665--5669",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Ireland Ltd",
number = "19",

}

TY - JOUR

T1 - The first pharmacophore model for potent NF-κB inhibitors

AU - Tsai, Keng-Chang

AU - Teng, Li-Wei

AU - Shao, Yi-Ming

AU - Chen, Yu-Chen

AU - Lee, Yu-Ching

AU - Li, Min-Yong

AU - Hsiao, Nai-Wan

N1 - 被引用次數:4 Export Date: 28 March 2016 CODEN: BMCLE 通訊地址: Hsiao, N.-W.; Institute of Biotechnology, National Changhua University of Education, Changhua, 50007, Taiwan; 電子郵件: nady@cc.ncue.edu.tw 化學物質/CAS: protein, 67254-75-5; Ligands; NF-kappa B 參考文獻: Sen, R., Baltimore, D., (1986) Cell, 46, p. 705; Beg, A.A., Baldwin Jr., A.S., (1993) Genes Dev., 7, p. 2064; Baeuerle, P.A., Henkel, T., (1994) Annu. Rev. Immunol., 12, p. 141; Verma, I.M., Stevenson, J.K., Schwarz, E.M., Van Antwerp, D., Miyamoto, S., (1995) Genes Dev., 9, p. 2723; Alkalay, I., Yaron, A., Hatzubai, A., Orian, A., Ciechanover, A., Ben-Neriah, Y., (1995) Proc. Natl. Acad. Sci. U.S.A., 92, p. 10599; Brown, K., Gerstberger, S., Carlson, L., Franzoso, G., Siebenlist, U., (1995) Science, 267, p. 1485; Scherer, D.C., Brockman, J.A., Chen, Z., Maniatis, T., Ballard, D.W., (1995) Proc. Natl. Acad. Sci. U.S.A., 92, p. 11259; Phelps, C.B., Sengchanthalangsy, L.L., Malek, S., Ghosh, G., (2000) J. Biol. Chem., 275, p. 24392; Berkowitz, B., Huang, D.B., Chen-Park, F.E., Sigler, P.B., Ghosh, G., (2002) J. Biol. Chem., 277, p. 24694; Schwartz, M.D., Moore, E.E., Moore, F.A., Shenkar, R., Moine, P., Haenel, J.B., Abraham, E., (1996) Crit. Care Med., 24, p. 1285; Gilston, V.J., Jones, H.W., Soo, C.C., Coumbe, A., Blades, S., Kaltschmidt, C., Baeuerle, P.A., Winyard, P.G., (1997) Biochem. Soc. Trans., 25, pp. 518S; Keates, S., Hitti, Y.S., Upton, M., Kelly, C.P., (1997) Gastroenterology, 113, p. 1099; Finco, T.S., Baldwin, A.S., (1995) Immunity, 3, p. 263; Baldwin Jr., A.S., (1996) Annu. Rev. Immunol., 14, p. 649; Barnes, P.J., Karin, M., (1997) N. Eng. J. Med., 336, p. 1066; Fiedler, M.A., Wernke-Dollries, K., Stark, J.M., (1998) Am. J. Respir. Cell Mol. Biol., 19, p. 259; Nunokawa, Y, Nakatsuka, T, Saitoh, M, Abe, K. World (PTC) Patent WO-0005234, 2000Tobe, M., Isobe, Y., Tomizawa, H., Nagasaki, T., Takahashi, H., Fukazawa, T., Hayashi, H., (2003) Bioorg. Med. Chem., 11, p. 383; Tobe, M., Isobe, Y., Tomizawa, H., Nagasaki, T., Takahashi, H., Hayashi, H., (2003) Bioorg. Med. Chem., 11, p. 3869; Li, H., Sutter, J., Hoffmann, R., (2000) Pharmacophore Preception, Development and Use in Drug Design, p. 171. , Guner, O. F, Ed, CA; http://www.accelrys.com, Catalyst. Version 4.11 software package, Accelry: San Diego, CA; 2005Debnath, A.K., (2002) J. Med. Chem., 45, p. 41; Du, L.P., Tsai, K.C., Li, M.Y., You, Q.D., Xia, L., (2004) Bioorg. Med. Chem. Lett., 14, p. 4771; Yang, Q., Du, L.P., Tsai, K.C., Wang, X.J., Li, M.Y., You, Q.D., (2009) QSAR Comb. Sci., 28, p. 59; Li, M.Y., Tsai, K.C., Xia, L., (2005) Bioorg. Med. Chem. Lett., 15, p. 657; Brooks, B.R., Bruccoleri, R.E., Olafson, B.D., States, D.J., Swaninathan, S., Karplus, M., (1983) J. Comput. Chem., 4, p. 187; Smellie, A., Teig, S.L., Tobwin, P., (1995) J. Comput. Chem., 16, p. 171; Sprague, P.W., (1995) Perspect. Drug Discovery Des., 3, p. 1; Baumann, B., Bohnenstengel, F., Siegmund, D., Wajant, H., Weber, C., Herr, I., Debatin, K.M., Wirth, T., (2002) J. Biol. Chem., 47, p. 44791; de-Blanco, E.J., Pandit, B., Hu, Z., Shi, J., Lewis, A., Li, P.K., (2007) Bioorg. Med. Chem. Lett., 17, p. 6031; Xie, Y.D.S., Thomas, C.J., Liu, Y., Zhang, Y.Q., Rinderspacher, A., Huang, W., Gong, G., Auld, D.S., (2008) Bioorg. Med. Chem. Lett., 18, p. 329; Muller, C.W., Rey, F.A., Sodeoka, M., Verdine, G.L., Harrison, S.C., (1995) Nature, 373, p. 311; Chen, F.E., Huang, D.B., Chen, Y.Q., Ghosh, G., (1998) Nature, 391, p. 410; Prasad, A.S., Bao, B., Beck, F.W., Sarkar, F.H., (2001) J. Lab Clin. Med., 138, p. 250; Pande, V., Sharma, R.K., Inoue, J., Otsuka, M., Ramos, M.J., (2003) J. Comput. Aided. Mol. Des., 17, p. 825; Sharma, R.K., Otsuka, M., Pande, V., Inoue, J., João Ramos, M., (2004) Bioorg Med Chem Lett., 14, p. 6123; Pante, V., Ramos, M.J., (2005) Bioorg. Med. Chem. Lett., 15, p. 4057; Piccagli, L.F.E., Borgatti, M., Bezzerri, V., Mancini, I., Nicolis, E., Dechecchi, M.C., Lampronti, I., Gambari, R., (2008) BMC Struct. Biol., 8, p. 38; gold is distributed by the Cambridge Crystallographic Data Center, Cambridge, UK, http://www.ccdc.ac.uk/prods/gold.htmlJones, G., Willett, P., Glen, R.C., (1995) J. Mol. Biol., 245, p. 43; Jones, G., Willett, P., Glen, R.C., Leach, A.R., Taylor, R., (1997) J. Mol. Biol., 267, p. 727

PY - 2009

Y1 - 2009

N2 - As an important transcription factor of the Ral family, nuclear factor-kappa B (NF-κB) is involved in numerous cellular processes, such as the responses to cellular stress and to inflammation. For better elucidating the quantitative structure-activity relationship of NF-κB inhibitors and determining possible ligand-protein interaction, a pharmacophore model, Hypo1, was built based on 35 training molecules by Catalyst/HypoGen algorithm. The five pharmacophore features of Hypo1, including three hydrophobic groups, one hydrogen-bond acceptor, and one hydrophobic aromatic group, were correctly mapped onto NF-κB surface. This model has strong capability to identify NF-κB inhibitors and to predict the activities of structurally diverse molecules, thus to provide a valuable tool in the design of new leads with desired biological activity by virtual screening. © 2009 Elsevier Ltd. All rights reserved.

AB - As an important transcription factor of the Ral family, nuclear factor-kappa B (NF-κB) is involved in numerous cellular processes, such as the responses to cellular stress and to inflammation. For better elucidating the quantitative structure-activity relationship of NF-κB inhibitors and determining possible ligand-protein interaction, a pharmacophore model, Hypo1, was built based on 35 training molecules by Catalyst/HypoGen algorithm. The five pharmacophore features of Hypo1, including three hydrophobic groups, one hydrogen-bond acceptor, and one hydrophobic aromatic group, were correctly mapped onto NF-κB surface. This model has strong capability to identify NF-κB inhibitors and to predict the activities of structurally diverse molecules, thus to provide a valuable tool in the design of new leads with desired biological activity by virtual screening. © 2009 Elsevier Ltd. All rights reserved.

KW - catalyst

KW - NF-κB inhibitor

KW - Pharmacophore

KW - QSAR

KW - I kappa B

KW - immunoglobulin enhancer binding protein

KW - ligand

KW - protein

KW - article

KW - hydrogen bond

KW - hydrophobicity

KW - pharmacophore

KW - protein interaction

KW - structure activity relation

KW - Binding Sites

KW - Combinatorial Chemistry Techniques

KW - Computer Simulation

KW - Ligands

KW - Models, Chemical

KW - NF-kappa B

KW - Quantitative Structure-Activity Relationship

KW - Software

U2 - 10.1016/j.bmcl.2009.08.021

DO - 10.1016/j.bmcl.2009.08.021

M3 - Article

VL - 19

SP - 5665

EP - 5669

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 19

ER -