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.
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。
相似文献
1
Design, synthesis and evaluation of monovalent Smac mimetics that bind to the BIR2 domain of the anti-apoptotic protein XIAP.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。
Bioorg Med Chem Lett. 2011 Jul 15;21(14):4332-6. doi: 10.1016/j.bmcl.2011.05.049. Epub 2011 May 24.
2
Design, synthesis and evaluation of inhibitor of apoptosis protein (IAP) antagonists that are highly selective for the BIR2 domain of XIAP.设计、合成及评估凋亡蛋白抑制因子（IAP）拮抗剂，其对 XIAP 的 BIR2 结构域具有高选择性。
Bioorg Med Chem Lett. 2013 Jul 15;23(14):4253-7. doi: 10.1016/j.bmcl.2013.04.096. Epub 2013 May 14.
3
Design, synthesis, and characterization of a potent, nonpeptide, cell-permeable, bivalent Smac mimetic that concurrently targets both the BIR2 and BIR3 domains in XIAP.一种强效、非肽、可穿透细胞的双价Smac模拟物的设计、合成与表征，该模拟物同时靶向XIAP中的BIR2和BIR3结构域。
J Am Chem Soc. 2007 Dec 12;129(49):15279-94. doi: 10.1021/ja074725f. Epub 2007 Nov 14.
4
Structure-based design, synthesis, evaluation, and crystallographic studies of conformationally constrained Smac mimetics as inhibitors of the X-linked inhibitor of apoptosis protein (XIAP).基于结构的构象受限Smac模拟物作为X连锁凋亡抑制蛋白（XIAP）抑制剂的设计、合成、评估及晶体学研究
J Med Chem. 2008 Nov 27;51(22):7169-80. doi: 10.1021/jm8006849.
5
Design and characterization of bivalent Smac-based peptides as antagonists of XIAP and development and validation of a fluorescence polarization assay for XIAP containing both BIR2 and BIR3 domains.基于Smac的双价肽作为XIAP拮抗剂的设计与表征以及针对包含BIR2和BIR3结构域的XIAP的荧光偏振测定法的开发与验证。
Anal Biochem. 2008 Mar 1;374(1):87-98. doi: 10.1016/j.ab.2007.10.032. Epub 2007 Nov 20.
6
Rational design, synthesis and characterization of potent, non-peptidic Smac mimics/XIAP inhibitors as proapoptotic agents for cancer therapy.强效非肽类Smac模拟物/XIAP抑制剂作为癌症治疗促凋亡药物的合理设计、合成及表征
Bioorg Med Chem. 2009 Aug 15;17(16):5834-56. doi: 10.1016/j.bmc.2009.07.009. Epub 2009 Jul 10.
7
Structural basis for bivalent Smac-mimetics recognition in the IAP protein family.IAP蛋白家族中双价Smac模拟物识别的结构基础。
J Mol Biol. 2009 Sep 25;392(3):630-44. doi: 10.1016/j.jmb.2009.04.033. Epub 2009 Apr 22.
8
Designing Smac-mimetics as antagonists of XIAP, cIAP1, and cIAP2.设计Smac模拟物作为X连锁凋亡抑制蛋白（XIAP）、细胞凋亡抑制蛋白1（cIAP1）和细胞凋亡抑制蛋白2（cIAP2）的拮抗剂。
Biochem Biophys Res Commun. 2009 Jan 9;378(2):162-7. doi: 10.1016/j.bbrc.2008.10.139. Epub 2008 Nov 4.
9
Theoretical studies on the interactions of XIAP-BIR3 domain with bicyclic and tricyclic core monovalent Smac mimetics.XIAP-BIR3 结构域与双环和三环核心单价 Smac 模拟物相互作用的理论研究。
J Mol Graph Model. 2010 Nov;29(3):354-62. doi: 10.1016/j.jmgm.2010.09.011. Epub 2010 Oct 25.
10
Novel SMAC-mimetics synergistically stimulate melanoma cell death in combination with TRAIL and Bortezomib.新型 SMAC 模拟物与 TRAIL 和硼替佐米联合协同刺激黑色素瘤细胞死亡。
Br J Cancer. 2010 Jun 8;102(12):1707-16. doi: 10.1038/sj.bjc.6605687. Epub 2010 May 11.
引用本文的文献
1
Pharmacological Activation of Non-canonical NF-κB Signaling Activates Latent HIV-1 Reservoirs .药理学激活非经典 NF-κB 信号可激活潜伏的 HIV-1 储库。
Cell Rep Med. 2020 Jun 23;1(3):100037. doi: 10.1016/j.xcrm.2020.100037.
2
Targeting the BIR Domains of Inhibitor of Apoptosis (IAP) Proteins in Cancer Treatment.在癌症治疗中靶向凋亡抑制蛋白（IAP）的BIR结构域
Comput Struct Biotechnol J. 2019 Jan 25;17:142-150. doi: 10.1016/j.csbj.2019.01.009. eCollection 2019.
3
Investigating isoquinoline derivatives for inhibition of inhibitor of apoptosis proteins for ovarian cancer treatment.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
Characterization of Potent SMAC Mimetics that Sensitize Cancer Cells to TNF Family-Induced Apoptosis.强效SMAC模拟物的特性研究：使癌细胞对肿瘤坏死因子家族诱导的凋亡敏感化
PLoS One. 2016 Sep 12;11(9):e0161952. doi: 10.1371/journal.pone.0161952. eCollection 2016.
6
A critical role for cellular inhibitor of protein 2 (cIAP2) in colitis-associated colorectal cancer and intestinal homeostasis mediated by the inflammasome and survival pathways.蛋白质2细胞抑制剂（cIAP2）在结肠炎相关结直肠癌以及由炎性小体和生存途径介导的肠道稳态中起关键作用。
Mucosal Immunol. 2016 Jan;9(1):146-58. doi: 10.1038/mi.2015.46. Epub 2015 Jun 3.
7
X-linked inhibitor of apoptosis protein - a critical death resistance regulator and therapeutic target for personalized cancer therapy.X 连锁凋亡抑制蛋白 - 一种关键的抵抗死亡调节因子，也是个性化癌症治疗的治疗靶点。
Front Oncol. 2014 Jul 28;4:197. doi: 10.3389/fonc.2014.00197. eCollection 2014.
8
Small-molecule IAP antagonists sensitize cancer cells to TRAIL-induced apoptosis: roles of XIAP and cIAPs.小分子 IAP 拮抗剂增敏 TRAIL 诱导的癌细胞凋亡：XIAP 和 cIAPs 的作用。
Mol Cancer Ther. 2014 Jan;13(1):5-15. doi: 10.1158/1535-7163.MCT-13-0153. Epub 2013 Nov 5.
9
The structure of XIAP BIR2: understanding the selectivity of the BIR domains.X连锁凋亡抑制蛋白BIR2结构：了解BIR结构域的选择性
Acta Crystallogr D Biol Crystallogr. 2013 Sep;69(Pt 9):1717-25. doi: 10.1107/S0907444913016284. Epub 2013 Aug 15.
10
Design, synthesis and evaluation of inhibitor of apoptosis protein (IAP) antagonists that are highly selective for the BIR2 domain of XIAP.设计、合成及评估凋亡蛋白抑制因子（IAP）拮抗剂，其对 XIAP 的 BIR2 结构域具有高选择性。
Bioorg Med Chem Lett. 2013 Jul 15;23(14):4253-7. doi: 10.1016/j.bmcl.2013.04.096. Epub 2013 May 14.
本文引用的文献
1
Potent bivalent Smac mimetics: effect of the linker on binding to inhibitor of apoptosis proteins (IAPs) and anticancer activity.强效双价 Smac 模拟物：连接子对凋亡蛋白抑制剂 (IAPs) 的结合和抗癌活性的影响。
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.环肽 Smac 模拟物作为 IAP 蛋白的拮抗剂。
Bioorg Med Chem Lett. 2010 May 15;20(10):3043-6. doi: 10.1016/j.bmcl.2010.03.114.
4
PHENIX: a comprehensive Python-based system for macromolecular structure solution.PHENIX：一个基于Python的用于大分子结构解析的综合系统。
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
IAP antagonists: promising candidates for cancer therapy.IAP 拮抗剂：癌症治疗的有前途的候选药物。
Drug Discov Today. 2010 Mar;15(5-6):210-9. doi: 10.1016/j.drudis.2010.01.003. Epub 2010 Jan 21.
7
Human caspases: activation, specificity, and regulation.人类半胱天冬酶：激活、特异性及调控
J Biol Chem. 2009 Aug 14;284(33):21777-21781. doi: 10.1074/jbc.R800084200. Epub 2009 May 26.
8
Design of small-molecule peptidic and nonpeptidic Smac mimetics.小分子肽类和非肽类Smac模拟物的设计。
Acc Chem Res. 2008 Oct;41(10):1264-77. doi: 10.1021/ar8000553.
9
IAP-targeted therapies for cancer.针对癌症的IAP靶向疗法。
Oncogene. 2008 Oct 20;27(48):6252-75. doi: 10.1038/onc.2008.302.
10
X-linked inhibitor of apoptosis protein as a therapeutic target.
Expert Opin Ther Targets. 2007 Nov;11(11):1459-71. doi: 10.1517/14728222.11.11.1459.
Zotero 插件