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

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 administrat...

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Bibliographic Details
Published in:PLOS Neglected Tropical Diseases
Main Authors: Thomas W von Geldern, Howard E Morton, Rick F Clark, Brian S Brown, Kelly L Johnston, Louise Ford, Sabine Specht, Robert A Carr, Deanne F Stolarik, Junli Ma, Matthew J Rieser, Dominique Struever, Stefan J Frohberger, Marianne Koschel, Alexandra Ehrens, Joseph D Turner, Marc P Hübner, Achim Hoerauf, Mark J Taylor, Stephen A Ward, Kennan Marsh, Dale J Kempf
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2019
Subjects:
Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Arctic
Online Access:https://doi.org/10.1371/journal.pntd.0007159
https://doaj.org/article/68bed1add1a349b9b6bff6345f18be14
Description
Summary: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.

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