AWZ1066S, a highly specific anti-Wolbachia drug candidate for a short-course treatment of filariasis
| Autor: | Paul M. O'Neill, Edward W. Tate, W. David Hong, Adam P. Roberts, Marc P. Hübner, Peter J. H. Webborn, Mark J. Taylor, Alexandra Ehrens, Stefan J. Frohberger, Dominique Struever, John Archer, Farid Benayoud, Joseph D. Turner, Rachel H. Clare, Achim Hoerauf, Stefan Kavanagh, Fabian Gusovsky, Andrew Steven, Neil G. Berry, Kelly L. Johnston, Ghaith Aljayyoussi, Andrew Cassidy, Remigiusz A. Serwa, Suet C. Leung, Janet Hemingway, Alasdair T. M. Hubbard, Gemma L. Nixon, Amy Siu, Stephen A. Ward, Emma A Murphy, Louise Ford, Li Qie, Motohiro Shiotani, Darren A. N. Cook |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Drug MACROFILARICIDAL ACTIVITY Phenotypic screening media_common.quotation_subject 030231 tropical medicine WUCHERERIA-BANCROFTI medicine.disease_cause Bioinformatics drug discovery Filariasis DOUBLE-BLIND 03 medical and health sciences Macrofilaricide chemistry.chemical_compound 0302 clinical medicine MD Multidisciplinary medicine BACTERIAL ENDOSYMBIONTS macrofilaricide lymphatic filariasis ELIMINATION Lymphatic filariasis media_common Science & Technology LITOMOSOIDES-SIGMODONTIS Multidisciplinary biology business.industry onchocerciasis ENDOBACTERIA anti-Wolbachia biology.organism_classification medicine.disease DOXYCYCLINE Multidisciplinary Sciences 030104 developmental biology Wuchereria bancrofti chemistry Neglected tropical diseases Science & Technology - Other Topics Wolbachia ALBENDAZOLE business |
| Zdroj: | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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