Identification of small molecules inhibitors of GCN5 histone acetyltransferase activity (189 views visite)
Arkivoc (ISSN: 1424-6376), 2006; 6(VIII): 24-37.
Paper type Tipo di articolo: Journal Article,
Impact factor: 0.8, 5-year impact factor Impact factor a 5 anni: 1.221
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-33744470562&partnerID=40&md5=736f517cf4e92d098c00f595b4211328
Keywords Parole chiave: Acetylation, Chromatin Remodelling, Gcn5, Yeast,
Affiliations Affiliazioni:
*** IBB - CNR ***
Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Universit degli Studi di Roma La Sapienza, P. le A. Moro 5, 00185 Roma, Italy
Dipartimento di Genetica e Biologia Molecolare, Universit degli Studi di Roma La Sapienza, P. le A. Moro 5, 00185 Roma, Italy
Dipartimento di Scienze Farmaceutiche, Universit degli Studi di Salerno, via Ponte Don Melillo, 84084 Fisciano (SA), Italy
Dipartimento di Patologia Generale, Seconda Universit degli Studi di Napoli, vico L. De Crecchio 7, 80138 Napoli, Italy
Centro di Oncogenomica AIRC, CEINGE Biotecnologia Avanzata, Napoli, Italy
Istituto di Biologia e Patologia Molecolari CNR, Dip. Genetica e Biologia Molecolare, Universit degli Studi di Roma La Sapienza, P. le A. Moro 5, 00185 Roma, Italy
References Riferimenti:
Davie, J.R., (1998) Curr. Opin. Genet. Dev., 8, p. 17
Kouzarides, T., (1999) Curr. Opin. Genet. Dev., 9, p. 40
Strahl, B.D., Allis, C.D., (2000) Nature, 403, p. 41
Pazin, M.J., Kadonaga, J.T., (1997) Cell, 89, p. 325
Glass, C.K., Rosenfeld, M.G., (2000) Genes Dev., 14, p. 121
Luger, K., Mader, A.W., Richmond, R.K., Sargent, D.F., Richmond, T.J., (1998) Nature, 389, p. 251
Urnov, F.D., Wolffe, A., (2000) Emerg. Ther. Targets, 4, p. 665
Fischle, W., Wang, Y., Allis, C.D., (2003) Curr. Opin. Cell Biol., 15, p. 172
Akey, C.W., Luger, K., (2003) Curr. Opin. Struc. Biol., 13, p. 6
Roth, S.Y., Denu, J.M., Allis, C.D., (2001) Annu. Rev. Biochem., 70, p. 81
Sterner, D.E., Berger, S.L., (2000) Microbiol. Mol. Biol. Rev., 64, p. 435
Marmorstein, R., (2001) J. Mol. Biol., 311, p. 433
Schiltz, R.L., Mizzen, C.A., Vassilev, A., Cook, R.G., Allis, C.D., Nakatani, Y., (1999) J. Biol. Chem., 274, p. 1189
Lau, O.D., Courtney, A.D., Vassilev, A., Marzilli, L.A., Cotter, R.J., Nakatani, Y., Cole, P.A., (2000) J. Biol. Chem., 275, p. 21953
Grant, P.A., Duggan, L., Cote, J., Roberts, S.M., Brownell, J.E., Candau, R., Ohba, R., Workman, J.L., (1997) Genes Dev., 11, p. 1640
Grant, P.A., Eberharter, A., John, S., Cook, R.G., Turner, B.M., Workman, J.L., (1999) J. Biol. Chem., 274, p. 5895
Mai, A., Massa, S., Rotili, D., Cerbara, I., Valente, S., Pezzi, R., Simeoni, S., Ragno, R., (2005) Med. Res. Rev., 25, p. 261
Minucci, S., Pelicci, P.G., (2006) Nat. Rev. Cancer, 6, p. 38
Muraoka, M., Konishi, M., Kikuchi-Yanoshita, R., Tanaka, K., Shitara, N., Chong, J.M., Iwama, T., Miyaki, M., (1996) Oncogene, 12, p. 1565
Sakakura, C., Hagiwara, A., Yasuoka, R., Fujita, Y., Nakanishi, M., Masuda, K., Kimura, A., Yamagishi, H., (2000) Int. J. Cancer, 89, p. 217
Puri, P.L., Sartorelli, V., Yang, X.J., Hamamori, Y., Ogryzko, V.V., Howard, B.H., Kedes, L., Levrero, M., (1997) Mol. Cell, 1, p. 35
Lehrmann, H., Pritchard, L.L., Harel-Bellan, A., (2002) Adv. Cancer Res., 86, p. 41
Zheng, Y., Thompson, P.R., Cebrat, M., Wang, L., Devlin, M.K., Alani, R.M., Cole, P.A., (2004) Methods Enzymol., 376, p. 188
Lau, O.D., Kundu, T.K., Soccio, R.E., Ait-Si-Ali, S., Khalil, E.M., Vassilev, A., Wolffe, A.P., Cole, P.A., (2000) Mol. Cell, 5, p. 589
Balasubramanyam, K., Swaminathan, V., Ranganathan, A., Kundu, T.K., (2003) J. Biol. Chem., 278, p. 19134
Biel, M., Kretsovali, A., Karatzali, E., Papamatheakis, J., Giannis, A., (2004) Angew. Chem. Int. Ed., 43, p. 3974
Stimson, L., Rowlands, M.G., Newbatt, Y.M., Smith, N.F., Raynaud, F.I., Rogers, P., Bavetsias, V., Aherne, G.W., (2005) Mol. Cancer Ther., 4, p. 1521
Massa, S., Mai, A., Sbardella, G., Esposito, M., Ragno, R., Loidl, P., Brosch, G., (2001) J. Med. Chem., 44, p. 2069
Ragno, R., Mai, A., Massa, S., Cerbara, I., Valente, S., Bottoni, P., Scatena, R., Brosch, G., (2004) J. Med. Chem., 47, p. 1351
Warrell Jr., R.P., Frankel, S.R., Miller Jr., W.H., Scheinberg, D.A., Itri, L.M., Hittelman, W.N., Vyas, R., Jakubowski, A.N., (1991) Engl. J. Med., 324, p. 1385
Han, J.W., Ahn, S.H., Park, S.H., Wang, S.Y., Bae, G.U., Seo, D.W., Known, H.K., Lee, H.W., (2000) Cancer Res., 60, p. 6068
Shute, R.E., Dunlap, B., Rich, D.H., (1987) J. Med. Chem., 30, p. 71
Ornaghi, P., Rotili, D., Sbardella, G., Mai, A., Filetici, P., (2005) Biochem. Pharmacol., 70, p. 911
Diana, G.D., McKinlay, M.A., Otto, M.J., Akullian, V., Oglesby, C., (1985) J. Med. Chem., 28, p. 1906
Ladner, D.W., (1986) Synthetic Commun., 16, p. 157
Ech-Chahad, A., Minassi, A., Berton, L., Appendino, G., (2005) Tetrahedron Lett., 46, p. 5113
Mori, K., Koseki, K., (1988) Tetrahedron, 44, p. 6013
Nyoung Kim, J., Mi Chung, Y., Jin Im, Y., (2002) Tetrahedron Lett., 43, p. 6209
Ma, Z., Hano, Y., Nomura, T., Chen, Y., (2004) Bioorg. Med. Chem. Lett., 14, p. 1193
Asao, N., Nogami, T., Lee, S., Yamamoto, Y., (2003) J. Amer. Chem. Soc., 125, p. 10921
Howe, L.A., Auston, D., Grant, P., John, S., Cook, R.G., Workman, J.L., Pillus, L., (2001) Genes Dev., 15, p. 3144
Arkivoc (ISSN: 1424-6376), 2006; 6(VIII): 24-37.
Paper type Tipo di articolo: Journal Article,
Impact factor: 0.8, 5-year impact factor Impact factor a 5 anni: 1.221
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-33744470562&partnerID=40&md5=736f517cf4e92d098c00f595b4211328
Keywords Parole chiave: Acetylation, Chromatin Remodelling, Gcn5, Yeast,
Affiliations Affiliazioni:
*** IBB - CNR ***
Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Universit degli Studi di Roma La Sapienza, P. le A. Moro 5, 00185 Roma, Italy
Dipartimento di Genetica e Biologia Molecolare, Universit degli Studi di Roma La Sapienza, P. le A. Moro 5, 00185 Roma, Italy
Dipartimento di Scienze Farmaceutiche, Universit degli Studi di Salerno, via Ponte Don Melillo, 84084 Fisciano (SA), Italy
Dipartimento di Patologia Generale, Seconda Universit degli Studi di Napoli, vico L. De Crecchio 7, 80138 Napoli, Italy
Centro di Oncogenomica AIRC, CEINGE Biotecnologia Avanzata, Napoli, Italy
Istituto di Biologia e Patologia Molecolari CNR, Dip. Genetica e Biologia Molecolare, Universit degli Studi di Roma La Sapienza, P. le A. Moro 5, 00185 Roma, Italy
References Riferimenti:
Davie, J.R., (1998) Curr. Opin. Genet. Dev., 8, p. 17
Kouzarides, T., (1999) Curr. Opin. Genet. Dev., 9, p. 40
Strahl, B.D., Allis, C.D., (2000) Nature, 403, p. 41
Pazin, M.J., Kadonaga, J.T., (1997) Cell, 89, p. 325
Glass, C.K., Rosenfeld, M.G., (2000) Genes Dev., 14, p. 121
Luger, K., Mader, A.W., Richmond, R.K., Sargent, D.F., Richmond, T.J., (1998) Nature, 389, p. 251
Urnov, F.D., Wolffe, A., (2000) Emerg. Ther. Targets, 4, p. 665
Fischle, W., Wang, Y., Allis, C.D., (2003) Curr. Opin. Cell Biol., 15, p. 172
Akey, C.W., Luger, K., (2003) Curr. Opin. Struc. Biol., 13, p. 6
Roth, S.Y., Denu, J.M., Allis, C.D., (2001) Annu. Rev. Biochem., 70, p. 81
Sterner, D.E., Berger, S.L., (2000) Microbiol. Mol. Biol. Rev., 64, p. 435
Marmorstein, R., (2001) J. Mol. Biol., 311, p. 433
Schiltz, R.L., Mizzen, C.A., Vassilev, A., Cook, R.G., Allis, C.D., Nakatani, Y., (1999) J. Biol. Chem., 274, p. 1189
Lau, O.D., Courtney, A.D., Vassilev, A., Marzilli, L.A., Cotter, R.J., Nakatani, Y., Cole, P.A., (2000) J. Biol. Chem., 275, p. 21953
Grant, P.A., Duggan, L., Cote, J., Roberts, S.M., Brownell, J.E., Candau, R., Ohba, R., Workman, J.L., (1997) Genes Dev., 11, p. 1640
Grant, P.A., Eberharter, A., John, S., Cook, R.G., Turner, B.M., Workman, J.L., (1999) J. Biol. Chem., 274, p. 5895
Mai, A., Massa, S., Rotili, D., Cerbara, I., Valente, S., Pezzi, R., Simeoni, S., Ragno, R., (2005) Med. Res. Rev., 25, p. 261
Minucci, S., Pelicci, P.G., (2006) Nat. Rev. Cancer, 6, p. 38
Muraoka, M., Konishi, M., Kikuchi-Yanoshita, R., Tanaka, K., Shitara, N., Chong, J.M., Iwama, T., Miyaki, M., (1996) Oncogene, 12, p. 1565
Sakakura, C., Hagiwara, A., Yasuoka, R., Fujita, Y., Nakanishi, M., Masuda, K., Kimura, A., Yamagishi, H., (2000) Int. J. Cancer, 89, p. 217
Puri, P.L., Sartorelli, V., Yang, X.J., Hamamori, Y., Ogryzko, V.V., Howard, B.H., Kedes, L., Levrero, M., (1997) Mol. Cell, 1, p. 35
Lehrmann, H., Pritchard, L.L., Harel-Bellan, A., (2002) Adv. Cancer Res., 86, p. 41
Zheng, Y., Thompson, P.R., Cebrat, M., Wang, L., Devlin, M.K., Alani, R.M., Cole, P.A., (2004) Methods Enzymol., 376, p. 188
Lau, O.D., Kundu, T.K., Soccio, R.E., Ait-Si-Ali, S., Khalil, E.M., Vassilev, A., Wolffe, A.P., Cole, P.A., (2000) Mol. Cell, 5, p. 589
Balasubramanyam, K., Swaminathan, V., Ranganathan, A., Kundu, T.K., (2003) J. Biol. Chem., 278, p. 19134
Biel, M., Kretsovali, A., Karatzali, E., Papamatheakis, J., Giannis, A., (2004) Angew. Chem. Int. Ed., 43, p. 3974
Stimson, L., Rowlands, M.G., Newbatt, Y.M., Smith, N.F., Raynaud, F.I., Rogers, P., Bavetsias, V., Aherne, G.W., (2005) Mol. Cancer Ther., 4, p. 1521
Massa, S., Mai, A., Sbardella, G., Esposito, M., Ragno, R., Loidl, P., Brosch, G., (2001) J. Med. Chem., 44, p. 2069
Ragno, R., Mai, A., Massa, S., Cerbara, I., Valente, S., Bottoni, P., Scatena, R., Brosch, G., (2004) J. Med. Chem., 47, p. 1351
Warrell Jr., R.P., Frankel, S.R., Miller Jr., W.H., Scheinberg, D.A., Itri, L.M., Hittelman, W.N., Vyas, R., Jakubowski, A.N., (1991) Engl. J. Med., 324, p. 1385
Han, J.W., Ahn, S.H., Park, S.H., Wang, S.Y., Bae, G.U., Seo, D.W., Known, H.K., Lee, H.W., (2000) Cancer Res., 60, p. 6068
Shute, R.E., Dunlap, B., Rich, D.H., (1987) J. Med. Chem., 30, p. 71
Ornaghi, P., Rotili, D., Sbardella, G., Mai, A., Filetici, P., (2005) Biochem. Pharmacol., 70, p. 911
Diana, G.D., McKinlay, M.A., Otto, M.J., Akullian, V., Oglesby, C., (1985) J. Med. Chem., 28, p. 1906
Ladner, D.W., (1986) Synthetic Commun., 16, p. 157
Ech-Chahad, A., Minassi, A., Berton, L., Appendino, G., (2005) Tetrahedron Lett., 46, p. 5113
Mori, K., Koseki, K., (1988) Tetrahedron, 44, p. 6013
Nyoung Kim, J., Mi Chung, Y., Jin Im, Y., (2002) Tetrahedron Lett., 43, p. 6209
Ma, Z., Hano, Y., Nomura, T., Chen, Y., (2004) Bioorg. Med. Chem. Lett., 14, p. 1193
Asao, N., Nogami, T., Lee, S., Yamamoto, Y., (2003) J. Amer. Chem. Soc., 125, p. 10921
Howe, L.A., Auston, D., Grant, P., John, S., Cook, R.G., Workman, J.L., Pillus, L., (2001) Genes Dev., 15, p. 3144
Starting from a yeast phenotypic screening performed on 21 chemically different substances we described the discovery of two small molecules as GCN5 inhibitors. The 2-methyl-3-carbethoxyquinoline 9 and its 2-desmethyl analogue 18 were able to significantly reduce the yeast cell growth, thus miming the effect of GCN5 deletion mutant. Tested to evaluate their effect on GCN5-dependent transcription of the HIS3 gene, 9 and 18 showed high inhibitory activity of gene transcription, more evident in activated conditions. Compound 9 was also able to reduce the acetylation levels of H3 and, to a lesser extent, H4 in yeast at 0.6 mM. In human leukemia U937 cells, at 1 mM concentration 9 showed 27% apoptosis induction, while 18 had just a little effect in the same conditions. Further studies on 9 and 18 will be performed to deepen their effects on GCN5-related phenomena.
No results. Nessun risultato. |
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