Yingjie Zhang - Discovery of a Tetrahydroisoquinoline-Based Hydroxamic Acid Derivative (ZYJ-34c) as Histone Deacetylase Inhibitor with Potent Oral Antitumor Activities.

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  Publication Details (including relevant citation   information):

  J Med.   Chem.,   2011, 54  (15),   5532-5539.


  Histone   deacetylase (HDACα) has emerged as an   attractive target for the development of antitumor agents during   the last decade. Previously tetrahydroisoquinoline-bearing   hydroxamic acid analogue, ZYJ-25e (1), was   identified and validated as a potent histone deacetylase   inhibitor (HDACi) with marked in vitro and in vivo antitumor   potency. In the present study, further modification of   1 led to another more potent, oral active HDACi,   ZYJ-34c (4). Compared to FDA-approved drug   suberoylanilide hydroxamic acid (SAHA), compound   4 exhibited higher in vivo antitumor potency in   a human breast carcinoma (MDA-MB-231) xenograft model and in a   mouse hepatoma-22 (H22) pulmonary metastasis model, and similar   in vivo antitumor potency in a human colon tumor (HCT116)   xenograft model.

  Address (URL): http://pubs.acs.org/doi/abs/10.1021/jm200577a