TY - JOUR
KW - Neglected tropical diseases (NTDs)
KW - Lymphatic filariasis (LF)
KW - Anti-Wolbachia
KW - Drug Discovery
KW - macrofilaricide
KW - onchocerciasis
AU - Hong DW
AU - Benayoud F
AU - Nixon GL
AU - Ford L
AU - Johnston KL
AU - Clare R
AU - Cassidy A
AU - Cook D
AU - Siu A
AU - Shiotani M
AU - Webborn PJ H
AU - Kavanagh S
AU - Aljayyoussi G
AU - Murphy E
AU - Steven A
AU - Archer J
AU - Struever D
AU - Frohberger S
AU - Ehrens A
AU - Hübner M
AU - Hoerauf A
AU - Roberts AP
AU - Hubbard AT M
AU - Tate E
AU - Serwa RA
AU - Leung SC
AU - Qie L
AU - Berry N
AU - Gusovsky F
AU - Hemingway J
AU - Turner J
AU - Taylor M
AU - Ward S
AU - O'Neill PM
AB - <p>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 &gt;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.</p>

BT - Proceedings of the National Academy of Sciences of the United States of America
C1 - <p>http://www.ncbi.nlm.nih.gov/pubmed/30617067?dopt=Abstract</p>

DO - 10.1073/pnas.1816585116
J2 - Proc. Natl. Acad. Sci. U.S.A.
LA - eng
N2 - <p>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 &gt;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.</p>

PY - 2019
T2 - Proceedings of the National Academy of Sciences of the United States of America
TI - AWZ1066S, a highly specific anti- drug candidate for a short-course treatment of filariasis.
UR - https://www.pnas.org/content/pnas/early/2019/01/02/1816585116.full.pdf
SN - 1091-6490
ER -