To optimize the lead compound of the UW series for Chagas disease
current phase of drug development
updated 15 Feb 2023
New candidates are needed to fill the pipeline for Chagas disease treatments. The UW series is a novel series of T. cruzi inhibitors based on a 2-aryl benzothiazole scaffold identified by Fred Buckner and his group at University of Washington. The lead compound, 45DAP076, is one of the very few compounds that provides single compound cure in an in vivo model of chronic Chagas disease up to 180 days after infection. A set of additional compounds based on the closely related scaffold are being prepared to further improve the efficacy and remove concerns associated with the lead compound.
Compound optimization of the UW series, aimed at the nomination of a pre-clinical candidate to advance to the next stage of development, progressed through 2022 with several leads showing improved properties and confirmation of single-compound cure in bioluminescent in vivo models. A chemically diverse backup series of compounds sharing the same putative mode of action were identified and are being optimized in parallel.
Compound optimization of the UW-series with a focus on optimizing the drug property profile of series compounds progressed significantly in 2021. A second generation of compounds has been confirmed to provide single-compound cure in an in vivo model of chronic Chagas disease up to 180 days after infection.
Efforts continued but were heavily impacted by the COVID-19 pandemic.
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