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设计、合成和评价与抗凋亡蛋白 XIAP 的 BIR2 结构域结合的单价 Smac 模拟物。

Design, synthesis and evaluation of monovalent Smac mimetics that bind to the BIR2 domain of the anti-apoptotic protein XIAP.

机构信息

Cancer Research Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

出版信息

Bioorg Med Chem Lett. 2011 Jul 15;21(14):4332-6. doi: 10.1016/j.bmcl.2011.05.049. Epub 2011 May 24.

DOI:10.1016/j.bmcl.2011.05.049
PMID:21680182
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3440873/
Abstract

We report the systematic rational design and synthesis of new monovalent Smac mimetics that bind preferentially to the BIR2 domain of the anti-apoptotic protein XIAP. Characterization of compounds in vitro (including 9i; ML101) led to the determination of key structural requirements for BIR2 binding affinity. Compounds 9h and 9j sensitized TRAIL-resistant breast cancer cells to apoptotic cell death, highlighting the value of these probe compounds as tools to investigate the biology of XIAP.

摘要

我们报告了新单价 Smac 类似物的系统合理设计和合成，这些类似物优先与抗凋亡蛋白 XIAP 的 BIR2 结构域结合。在体外对化合物（包括 9i；ML101）的表征导致确定了 BIR2 结合亲和力的关键结构要求。化合物 9h 和 9j 使 TRAIL 耐药乳腺癌细胞对细胞凋亡敏感，突出了这些探针化合物作为研究 XIAP 生物学的工具的价值。

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1
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J Med Chem. 2011 May 12;54(9):3306-18. doi: 10.1021/jm101651b. Epub 2011 Apr 13.
2
Characterization of dequalinium as a XIAP antagonist that targets the BIR2 domain.鉴定地喹氯铵是一种 XIAP 拮抗剂，靶向 BIR2 结构域。
Apoptosis. 2011 May;16(5):460-7. doi: 10.1007/s10495-011-0582-4.
3
Cyclopeptide Smac mimetics as antagonists of IAP proteins.
研究异喹啉衍生物对凋亡抑制蛋白的抑制作用以用于卵巢癌治疗。
Drug Des Devel Ther. 2017 Sep 11;11:2697-2707. doi: 10.2147/DDDT.S137608. eCollection 2017.
4
Inducing death in tumor cells: roles of the inhibitor of apoptosis proteins.诱导肿瘤细胞死亡：凋亡抑制蛋白的作用
F1000Res. 2017 Apr 27;6:587. doi: 10.12688/f1000research.10625.1. eCollection 2017.
5
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PLoS One. 2016 Sep 12;11(9):e0161952. doi: 10.1371/journal.pone.0161952. eCollection 2016.
6
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Mucosal Immunol. 2016 Jan;9(1):146-58. doi: 10.1038/mi.2015.46. Epub 2015 Jun 3.
7
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8
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9
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10
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Bioorg Med Chem Lett. 2010 May 15;20(10):3043-6. doi: 10.1016/j.bmcl.2010.03.114.
4
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Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21. doi: 10.1107/S0907444909052925. Epub 2010 Jan 22.
5
Small-molecule pan-IAP antagonists: a patent review.小分子泛 IAP 拮抗剂：专利研究综述。
Expert Opin Ther Pat. 2010 Feb;20(2):251-67. doi: 10.1517/13543770903567077.
6
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7
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J Biol Chem. 2009 Aug 14;284(33):21777-21781. doi: 10.1074/jbc.R800084200. Epub 2009 May 26.
8
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9
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Oncogene. 2008 Oct 20;27(48):6252-75. doi: 10.1038/onc.2008.302.
10
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Expert Opin Ther Targets. 2007 Nov;11(11):1459-71. doi: 10.1517/14728222.11.11.1459.