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

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von Geldern, Thomas W, Morton, Howard E, Clark, Rick F, Brown, Brian S, Johnston, Kelly, Ford, Louise, Specht, Sabine, Carr, Robert A, Stolarik, Deanne F, Ma, Junli, Rieser, Matthew J, Struever, Dominique, Frohberger, Stefan J, Koschel, Marianne, Ehrens, Alexandra, Turner, Joseph, Hübner, Marc P, Hoerauf, Achim, Taylor, Mark, Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192, Marsh, Kennan and Kempf, Dale J (2019) 'Discovery of ABBV-4083, a novel analog of Tylosin A that has potent anti-Wolbachia and anti-filarial activity.'. PLoS Neglected Tropical Diseases, Vol 13, Issue 2, e0007159.

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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.

Item Type: Article
Subjects: QW Microbiology and Immunology > Bacteria > QW 150 Proteobacteria. Rickettsiaceae, Wolbachia
WA Public Health > Preventive Medicine > WA 108 Preventive health services. Preventive medicine. Travel Medicine.
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General)
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.pntd.0007159
Depositing User: Stacy Murtagh
Date Deposited: 12 Mar 2019 16:57
Last Modified: 14 Mar 2019 12:39
URI: https://archive.lstmed.ac.uk/id/eprint/10341

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