pubs.acs.org/acsmedchemlett
ACKNOWLEDGMENT We are thankful to Felice Deceglie for
the artwork.
ABBREVIATIONS HDAC, histone deacetylase; ATRA, all-
trans retinoic acid; RO, rank order; SAHA, suberoylanilide
hydroxamic acid; TSA, trycostatin A; DP, differentiation
potency; IC50, inhibitory concentration 50, the concentra-
tion causing 50% of the maximal inhibitory effect.
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Figure 2. In vivo antitumor activity of compounds 21d and 21e. Nude
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SUPPORTING INFORMATION AVAILABLE Experimental
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pounds, Table 1, and Figures 1 and 2. This material is available free
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AUTHOR INFORMATION
Corresponding Author: *To whom correspondence should be
addressed. Tel: 39-02-39014533. Fax: 39-02-39014744. E-mail:
Author Contributions: A.B., M.G., C.V., and M.T. carried out all
of the biological experiments with NB4 cells; M.F. performed all of
the biocomputing analyses; M.B., M.B., and M.P. designed and
supervised the in vivo experiments and the experiments involving
HDAC isoform inhibition; A.G. and C.A.M. modeled and supervised
the structural rationale of the compounds; M.G. synthesized and
characterized the compounds described in the paper; and E.G.
designed and supervised the entire work.
Funding Sources: This work was partially supported by grants to
E.G. from the Associazione Italiana per la Ricerca contro il Cancro
(AIRC), Fondazione Italo Monzino, Ministero della Ricerca (Progetti
Finalizzati) and an unrestricted grant to E.G. from Menarini Indus-
trie Farmaceutiche Riunite. The financial support of the above-
mentioned agencies and charities is acknowledged.
(15) Gianni, M.; Li Calzi, M.; Terao, M.; Guiso, G.; Caccia, S.;
Barbui, T.; Rambaldi, A.; Garattini, E. AM580, a stable benzoic
derivative of retinoic acid, has powerful and selective cyto-
differentiating effects on acute promyelocytic leukemia cells.
Blood 1996, 87, 1520–1531.
Notes: M.B., A.G., M.G., M.B., M.P., and C.A.M. are full-time employees
of Menarini Industrie Farmaceutiche Riunite, which holds the patent for
all of the HDAC inhibitors described in this paper.
r
2010 American Chemical Society
415
DOI: 10.1021/ml1001163 ACS Med. Chem. Lett. 2010, 1, 411–415
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