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个人信息Personal Information
教授
博士生导师
硕士生导师
性别：女
毕业院校：大连理工大学
学位：博士
所在单位：化学学院
学科：化学生物学. 药理学. 细胞生物学
办公地点：Chemical complex building,D513
联系方式：zczhang@dlut.edu.cn 13942696903
电子邮箱：zczhang@dlut.edu.cn
3-Thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (S1) Based Molecules as Potent, Dual Inhibitors of B-Cell Lymphoma 2 (Bcl-2) and Myeloid Cell Leukemia Sequence 1 (Mcl-1): Structure-Based Design and Structure-Activity Relationship
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论文类型：期刊论文
发表时间：2011-02-24
发表刊物：JOURNAL OF MEDICINAL CHEMISTRY
收录刊物：Scopus、SCIE、PubMed
卷号：54
期号：4
页面范围：1101-1105
ISSN号：0022-2623
摘要：We recently described the discovery of a dual inhibitor of Bcl-2 and Mcl-1, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (3, S1). Here we report a structure-guided design in combination with structure activity relationship studies to exploit the difference in the p2 binding pocket of Bcl-2 and Mcl-1, from which a novel dual inhibitor 3-(4-aminophenylthio)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (6h) was obtained, which showed significant enhanced IC(50) value against Mcl-1 (5 nM), greater Mcl-1/Bak disruption potential, and accordingly a 10-fold increased cytotoxicity over 3.