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个人信息Personal Information
副教授
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：医学部
学科：有机化学. 细胞生物学
办公地点：大连理工大学西部新校区化学综合楼C508
联系方式：Email: songting@dlut.edu.cn Tel: 18098885828
电子邮箱：songting@dlut.edu.cn
Novel soluble myeloid cell leukemia sequence 1 (Mcl-1) inhibitor (E,E)-2-(benzylaminocarbonyl)-3-styrylacrylonitrile (4g) developed using a fragment-based approach
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论文类型：期刊论文
发表时间：2013-01-01
发表刊物：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
收录刊物：SCIE、PubMed、Scopus
卷号：59
页面范围：141-149
ISSN号：0223-5234
关键字：Mcl-1; Small molecule inhibitor; Fragment-based approach; Anticancer
摘要：Based on a known nanomolar Bcl-2 homology domain 3 (BH3) mimetic 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b] pyrrole-9-carbonitrile (SI, MW: 331), we applied a fragment-based approach to obtain BH3 mimetics with improved affinity and improved solubility in a water ethanol (9:1) cosolvent. After the deconstruction of 1 (S1), we obtained fragment cyanoacetamide (4), which was determined to be a ligand efficiency (LE) hot part. After a rational optimization through fragment evolution beginning with fragment 4, a smaller Mcl-1 inhibitor (E,E)-2-(benzylaminocarbonyl)-3-styrylacrylonitrile (4g, MW: 288) with a 6-fold increase in affinity compared to I was obtained, as predicted by our optimization curve and identified by Mcl-1 protein nuclear magnetic resonance (NMR). (C) 2012 Elsevier Masson SAS. All rights reserved.