Hong, W David, Benayoud, Farid, Nixon, Gemma L, Ford, Louise, Johnston, Kelly L, Clare, Rachel H, Cassidy, Andrew, Cook, Darren AN, Siu, Amy, Shiotani, Motohiro et al (show 24 more authors)
(2019)
AWZ1066S, a highly specific anti-Wolbachia drug candidate for a short-course treatment of filariasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 116 (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, Wolbachia, using antibiotics, can lead to permanent sterilization of adult female parasites and a safe macrofilaricidal outcome. AWZ1066S is a highly specific anti-Wolbachia 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-Wolbachia 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 |
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Uncontrolled Keywords: | onchocerciasis, lymphatic filariasis, anti-Wolbachia, drug discovery, macrofilaricide |
Depositing User: | Symplectic Admin |
Date Deposited: | 24 Apr 2019 13:41 |
Last Modified: | 19 Jan 2023 00:53 |
DOI: | 10.1073/pnas.1816585116 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3038180 |
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AWZ1066S, a highly specific anti-Wolbachia drug candidate for a short-course treatment of filariasis. (deposited 17 Jan 2019 11:40)
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