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