Identification of small molecules inhibitors of GCN5 histone acetyltransferase activity(214 views visite) Mai A, Rotili D, Ornaghi P, Tosi F, Vicidomini C, Sardella G, Nebbioso A, Altucci L, Filatici P
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
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
Identification of small molecules inhibitors of GCN5 histone acetyltransferase activity
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.
Identification of small molecules inhibitors of GCN5 histone acetyltransferase activity
No results. Nessun risultato.
Identification of small molecules inhibitors of GCN5 histone acetyltransferase activity
Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L * Combined HAT/EZH2 modulation leads to cancer-selective cell death(206 visite) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 DettagliEsporta in BibTeXEsporta in EndNote
17 Records (17 escludendo Abstract e Conferenze). Impact factor totale: 94.601 (94.601 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 98.127 (98.127 escludendo Abstract e Conferenze).
Last modified by Ultima modifica di Massimiliano Sorbillo on in data Sunday 12 July 2020, 13:15:07 214 views visite. Last view on Ultima visita in data Friday 26 February 2021, 10:59:41