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AWZ1066S, a highly specific anti- drug candidate for a short-course treatment of filariasis.

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Hong, W David, Benayoud, Farid, Nixon, Gemma L, Ford, Louise, Johnston, Kelly, Clare, Rachel ORCID: https://orcid.org/0000-0002-3945-0530, Cassidy, Andrew, Cook, Darren A N, Siu, Amy, Shiotani, Motohiro, Webborn, Peter J H, Kavanagh, Stefan, Aljayyoussi, Ghaith, Murphy, Emma, Steven, Andrew, Archer, John, Struever, Dominique, Frohberger, Stefan J, Ehrens, Alexandra, Hübner, Marc P, Hoerauf, Achim, Roberts, Adam, Hubbard, Alasdair ORCID: https://orcid.org/0000-0001-6668-9179, Tate, Edward W, Serwa, Remigiusz A, Leung, Suet C, Qie, Li, Berry, Neil G, Gusovsky, Fabian, Hemingway, Janet, Turner, Joseph, Taylor, Mark, Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192 and O'Neill, Paul M (2019) 'AWZ1066S, a highly specific anti- drug candidate for a short-course treatment of filariasis.'. Proceedings of the National Academy of Sciences of the United States of America, Vol 116, Issue 4, pp. 1414-1419.

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Abstract

Onchocerciasis and lymphatic filariasis are two neglected tropical diseases that together affect ∼157 million people and inflict severe disability. Both diseases are caused by parasitic filarial nematodes with elimination efforts constrained by the lack of a safe drug that can kill the adult filaria (macrofilaricide). Previous proof-of-concept human trials have demonstrated that depleting >90% of the essential nematode endosymbiont bacterium, , using antibiotics, can lead to permanent sterilization of adult female parasites and a safe macrofilaricidal outcome. AWZ1066S is a highly specific anti- candidate selected through a lead optimization program focused on balancing efficacy, safety and drug metabolism/pharmacokinetic (DMPK) features of a thienopyrimidine/quinazoline scaffold derived from phenotypic screening. AWZ1066S shows superior efficacy to existing anti- therapies in validated preclinical models of infection and has DMPK characteristics that are compatible with a short therapeutic regimen of 7 days or less. This candidate molecule is well-positioned for onward development and has the potential to make a significant impact on communities affected by filariasis.

Item Type: Article
Subjects: QW Microbiology and Immunology > Bacteria > QW 150 Proteobacteria. Rickettsiaceae, Wolbachia
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 850 Nematode infections (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 885 Onchocerciasis
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1073/pnas.1816585116
Depositing User: Stacy Murtagh
Date Deposited: 10 Jan 2019 13:31
Last Modified: 23 Jan 2019 10:42
URI: http://archive.lstmed.ac.uk/id/eprint/9949

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