Molecular, Macromolecular, and Supramolecular Glucuronide Prodrugs: Lead Identified for Anticancer Prodrug Monotherapy

Jarlstad Olesen Morten T.; Walther Raoul; Poier Pier Paolo; Dagn?s‐Hansen Frederik; Zelikin Alexander N.

摘要

Abstract >In this work, a tumor growth intervention by localized drug synthesis within the tumor volume, using the enzymatic repertoire of the tumor itself, is presented. Towards the overall success, molecular, macromolecular, and supramolecular glucuronide prodrugs were designed for a highly potent toxin, monomethyl auristatin E (MMAE). The lead candidate exhibited a fold difference in toxicity between the prodrug and the drug of 175, had an engineered mechanism to enhance the deliverable payload to tumours, and contained a highly potent toxin such that bioconversion of only a few prodrug molecules created a concentration of MMAE sufficient enough for efficient suppression of tumor growth. Each of these points is highly significant and together afford a safe, selective anticancer measure, making tumor‐targeted glucuronides attractive for translational medicine. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><Abstract Type =“Main”XML：Lang =“en”> <标题类型=“main”>抽象</ title> 在这项工作中，使用肿瘤体积内的局部药物合成的肿瘤生长干预，使用肿瘤本身的酶促曲目。朝向整体成功，分子，大分子和超分子葡萄糖醛酸葡萄糖前药专为高效的毒素，单甲基Auristatin E（MMAE）设计。铅候选者在前药和药物中含有175的药物之间的毒性差异，具有改进的机制，以增强可输送的有效载荷对肿瘤，并含有高度有效的毒素，使得只有几个前药分子的生物转化产生了mmae的浓度足够足以有效抑制肿瘤生长。这些点中的每一个都非常重要，共同提供安全，选择性的抗癌措施，使肿瘤靶向葡糖醛糖苷对转化药具有吸引力。</ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-19011/'>《Angewandte Chemie》</a> <b style="margin: 0 2px;">|</b><span>2020年第19期</span><b style="margin: 0 2px;">|</b><span>共7页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Jarlstad Olesen Morten T.&option=202" target="_blank" rel="nofollow">Jarlstad Olesen Morten T.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Walther Raoul&option=202" target="_blank" rel="nofollow">Walther Raoul;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Poier Pier Paolo&option=202" target="_blank" rel="nofollow">Poier Pier Paolo;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Dagn?s‐Hansen Frederik&option=202" target="_blank" rel="nofollow">Dagn?s‐Hansen Frederik;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zelikin Alexander N.&option=202" target="_blank" rel="nofollow">Zelikin Alexander N.;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Department of ChemistryAarhus UniversityAarhus Denmark;</p> <p>Department of ChemistryAarhus UniversityAarhus Denmark;</p> <p>Department of ChemistryAarhus UniversityAarhus Denmark;</p> <p>Department of BiomedicineAarhus UniversityAarhus Denmark;</p> <p>Department of ChemistryAarhus UniversityAarhus Denmark;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/1188.html" title="应用化学">应用化学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=cancer&option=203" rel="nofollow">cancer;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=glucuronides&option=203" rel="nofollow">glucuronides;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=drug delivery&option=203" rel="nofollow">drug delivery;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=enzymes&option=203" rel="nofollow">enzymes;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=prodrugs&option=203" rel="nofollow">prodrugs;</a> </p> <div class="translation"> 机译：癌症;葡糖醛糖苷;药物递送;酶;前药; 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