增加靶时间：利用半胱氨酸蛋白酶抑制剂来增强受体靶向药物在肿瘤中的滞留。
Increasing time on target: utilization of inhibitors of cysteine cathepsins to enhance the tumor retention of receptor-targeted agents.
机构信息
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 985830 Nebraska Medical Center, Omaha, NE 68198, USA.
出版信息
Chem Commun (Camb). 2018 Oct 4;54(80):11268-11271. doi: 10.1039/c8cc05982a.
Abstract
We report a strategy of utilizing irreversible cysteine cathepsin inhibitor as trapping agent to increase the tumor residence time of receptor-targeted agents. The targeted constructs incorporating these cysteine cathepsin trapping agents were able to form high molecular weight adducts with intracellular cysteine cathepsins, thus achieving superior retention in tumor tissues.
摘要
我们报告了一种利用不可逆的半胱氨酸组织蛋白酶抑制剂作为捕获剂来增加受体靶向剂在肿瘤中的驻留时间的策略。结合这些半胱氨酸组织蛋白酶捕获剂的靶向构建体能够与细胞内的半胱氨酸组织蛋白酶形成高分子量加合物，从而在肿瘤组织中实现更好的保留。
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2
Evaluation of DOTA-chelated neurotensin analogs with spacer-enhanced biological performance for neurotensin-receptor-1-positive tumor targeting.
Nucl Med Biol. 2015 Nov;42(11):816-23. doi: 10.1016/j.nucmedbio.2015.07.010. Epub 2015 Jul 29.
3
Cathepsin L targeting in cancer treatment.
Pharmacol Ther. 2015 Nov;155:105-16. doi: 10.1016/j.pharmthera.2015.08.007. Epub 2015 Aug 20.
4
Design of Protease Activated Optical Contrast Agents That Exploit a Latent Lysosomotropic Effect for Use in Fluorescence-Guided Surgery.
ACS Chem Biol. 2015 Sep 18;10(9):1977-88. doi: 10.1021/acschembio.5b00205. Epub 2015 Jun 24.
5
A novel cysteine cathepsin inhibitor yields macrophage cell death and mammary tumor regression.
Oncogene. 2015 Dec 10;34(50):6066-78. doi: 10.1038/onc.2015.51. Epub 2015 Mar 23.
6
The current stage of cathepsin B inhibitors as potential anticancer agents.
Future Med Chem. 2014 Jul;6(11):1355-71. doi: 10.4155/fmc.14.73.
7
Cathepsin B: multiple roles in cancer.
Proteomics Clin Appl. 2014 Jun;8(5-6):427-37. doi: 10.1002/prca.201300105. Epub 2014 Mar 26.
8
Neurotensin and its high affinity receptor 1 as a potential pharmacological target in cancer therapy.
Front Endocrinol (Lausanne). 2013 Jan 17;3:184. doi: 10.3389/fendo.2012.00184. eCollection 2012.
9
Radiolabeled peptides: valuable tools for the detection and treatment of cancer.
Theranostics. 2012;2(5):481-501. doi: 10.7150/thno.4024. Epub 2012 May 16.
10
Cysteine cathepsins: from structure, function and regulation to new frontiers.
Biochim Biophys Acta. 2012 Jan;1824(1):68-88. doi: 10.1016/j.bbapap.2011.10.002. Epub 2011 Oct 12.
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