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发现 ABBV-4083，一种泰乐菌素 A 的新型类似物，具有强大的抗沃尔巴克氏体和抗丝虫活性。

Discovery of ABBV-4083, a novel analog of Tylosin A that has potent anti-Wolbachia and anti-filarial activity.

机构信息

Global Pharmaceutical Research and Development, AbbVie, North Chicago, Illinois, United States of America.

Franciscan Institute for World Health, Franciscan University, Steubenville, Ohio, United States of America.

出版信息

PLoS Negl Trop Dis. 2019 Feb 28;13(2):e0007159. doi: 10.1371/journal.pntd.0007159. eCollection 2019 Feb.

DOI:10.1371/journal.pntd.0007159
PMID:30818326
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6413952/
Abstract

There is a significant need for improved treatments for onchocerciasis and lymphatic filariasis, diseases caused by filarial worm infection. In particular, an agent able to selectively kill adult worms (macrofilaricide) would be expected to substantially augment the benefits of mass drug administration (MDA) with current microfilaricides, and to provide a solution to treatment of onchocerciasis / loiasis co-infection, where MDA is restricted. We have identified a novel macrofilaricidal agent, Tylosin A (TylA), which acts by targeting the worm-symbiont Wolbachia bacterium. Chemical modification of TylA leads to improvements in anti-Wolbachia activity and oral pharmacokinetic properties; an optimized analog (ABBV-4083) has been selected for clinical evaluation.

摘要

治疗盘尾丝虫病和象皮病（由丝虫感染引起的疾病）的方法亟待改进。特别是，如果有一种药物能够选择性杀死成虫（杀微丝蚴剂），那么它将有望大大提高目前微丝蚴药物治疗的效果，并为治疗盘尾丝虫病/罗阿丝虫病合并感染提供一种解决方案，因为目前 MDA 治疗受到限制。我们已经发现了一种新型的杀微丝蚴剂泰乐菌素 A（TylA），它通过靶向虫共生菌沃尔巴克氏体发挥作用。对 TylA 进行化学修饰可提高其抗沃尔巴克氏体活性和口服药代动力学特性；一种经过优化的类似物（ABBV-4083）已被选入临床评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba3c/6413952/0cd31a8f1f3f/pntd.0007159.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba3c/6413952/dbe7fa40ab0e/pntd.0007159.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba3c/6413952/0b5d5f362fb0/pntd.0007159.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba3c/6413952/0cd31a8f1f3f/pntd.0007159.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba3c/6413952/dbe7fa40ab0e/pntd.0007159.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba3c/6413952/0b5d5f362fb0/pntd.0007159.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba3c/6413952/0cd31a8f1f3f/pntd.0007159.g003.jpg

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