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



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). 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
Uncontrolled Keywords: onchocerciasis, lymphatic filariasis, anti-Wolbachia, drug discovery, macrofilaricide
Depositing User: Symplectic Admin
Date Deposited: 24 Apr 2019 13:41
Last Modified: 13 Jan 2021 17:11
DOI: 10.1073/pnas.1816585116
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3038180

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