张志超

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

扫描关注

论文成果

当前位置: 中文主页 >> 科学研究 >> 论文成果

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

点击次数:

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.