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

详细信息    查看全文

• 作者：Yingjie Zhang ; Hao Fang ; Jinhong Feng ; Yuping Jia ; Xuejian Wang ; Wenfang Xu
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：August 11, 2011
• 年：2011
• 卷：54
• 期：15
• 页码：5532-5539
• 全文大小：962K
• 年卷期：v.54,no.15(August 11, 2011)
• ISSN：1520-4804

文摘

Histone deacetylase (HDAC) has emerged as an attractive target for the development of antitumor agents during the past 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, orally 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.