Inhibitors of the anti-apoptotic Bcl-2 proteins: a patent review

被引：88
作者：
Bajwa, Naval [1 ]
Liao, Chenzhong [1 ]
Nikolovska-Coleska, Zaneta [1 ]
机构：
[1] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA
来源：
EXPERT OPINION ON THERAPEUTIC PATENTS | 2012年 / 22卷 / 01期
基金：
美国国家卫生研究院;
关键词：
apoptosis; BH3; mimetics; cancer; inhibitors of anti-apoptotic Bcl-2 proteins; protein-protein interactions; SMALL-MOLECULE INHIBITOR; BH3 MIMETIC ABT-737; ACUTE LYMPHOBLASTIC-LEUKEMIA; PAN-BCL-2 FAMILY ANTAGONIST; PAN-ACTIVE INHIBITORS; CANCER-CELL-LINES; PHASE-I; OBATOCLAX MESYLATE; PROSTATE-CANCER; APOGOSSYPOL DERIVATIVES;
D O I：
10.1517/13543776.2012.644274
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Introduction: The B-cell lymphoma-2 (Bcl-2) family of proteins is central to the regulation of apoptosis, which is vital for proper tissue development and cellular homeostasis. Anti-apoptotic proteins, members of the Bcl-2 family, are an important survival factor for many cancers and their overexpression has been associated with tumor initiation, progression, and resistance to current anticancer therapies. Therefore, strategies seeking to antagonize the function of Bcl-2 anti-apoptotic proteins have been extensively studied for developing a novel cancer therapy. Areas covered: This review covers research and patent literature of the last 15 years dealing with the discovery and development of inhibitors of the Bcl-2 protein family. Expert opinion: The feasibility of disrupting protein-protein interactions between anti-apoptotic and pro-apoptotic proteins, members of the Bcl-2 family, using peptidomimetics and small-molecule inhibitors has been successfully established. Three small-molecule inhibitors have entered human clinical trials, which will allow the evaluation of this potential therapeutic approach in cancer patients. It will be important to gain a better understanding of pan and selective Bcl-2 inhibitors in order to facilitate future drug design efforts.
引用
收藏
页码：37 / 55
页数：19
相关论文
共 151 条
[1]  
ABBOTT LAB, 2005, Patent No. 2005069771
[2]  
Abbott Laboratories, 2010, Patent No. [US7750004B2, 7750004]
[3]  
Abbott Laboratories, 2007, Patent No. [US20070072860, 20070072860]
[4]  
Abbott Laboratories, 2002, Patent No. [WO2002024636, 2002024636]
[5]  
Abbott Laboratories, 2005, Patent No. [WO2005117543A2, 2005117543]
[6]  
Abbott Laboratories, 2010, Patent No. [US7767684, 7767684]
[7]  
Abbott Laboratories, 2011, Patent No. [US7906505, 7906505]
[8]  
Abbott Laboratories, 2011, Patent No. [US7973161, 7973161]
[9]  
Abbott Laboratories, 2010, Patent No. [WO2010065865A2, 2010065865]
[10]  
Abbott Laboratories, 2006, Patent No. [WO2006127364A1, 2006127364]
12345678910