Accès ouvert
2026
article
OpenAlex
Camila Colombari Mantovani, Flávia Regina Novais de Freitas, Carolina Borsoi Moraes, Guilherme Rodrigo Reis Monteiro dos Santos et autres
There are restricted treatment options for Chagas disease, a global health risk causing 12,000 fatalities annually. This situation is exacerbated by environmental changes and migration, which is altering patterns of disease transmission, and by expansion of the vector range. The disease is …
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2026
article
OpenAlex
Rasmus Hansen Henninger, Wietse M. Schouten, Byron A. Arana, Jean‐Yves Gillon et autres
ABSTRACT Cutaneous leishmaniasis is a neglected tropical disease with only one oral treatment option. DNDI‐6148 is an orally bioavailable compound with potent antiparasitic activity in preclinical studies. Establishing skin target‐site pharmacokinetic/pharmacodynamic (PK/PD) relationships is essential to enable its clinical development. The objective …
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Accès ouvert
2025
article
OpenAlex
Thamires Quadros Froes, Temitayo Omowumi Alegbejo Price, Bruna Fleck Godoi, Miguel de Menezes Vaidergorn et autres
Abstract Covalent drug design applied to parasite proteins enables selective therapies by targeting nucleophilic residues of macromolecules. We present the first covalent inhibitors of Leishmania braziliensis dihydroorotate dehydrogenase (LbDHODH), a key enzyme in pyrimidine biosynthesis with a reactive cysteine (Cys131) in its …
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Accès ouvert
2025
article
OpenAlex
Wietse M. Schouten, Katrien Van Bocxlaer, Hilde Rosing, Alwin D. R. Huitema et autres
Understanding the target site pharmacokinetics (PK) of the nitroimidazole analog DNDI-0690, a potential drug for the neglected parasitic disease leishmaniasis, is important due to the diversity of infected tissue sites and potential drug penetration variability. An ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) …
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Accès ouvert
2025
article
OpenAlex
Wietse M. Schouten, Katrien Van Bocxlaer, Hilde Rosing, Alwin D. R. Huitema et autres
Leishmaniasis is a neglected parasitic infection that continues to pose a significant global health challenge, with currently limited effective treatment options. DNDI-6174 is a novel orally-active, investigational drug with antileishmanial properties. Herein, a novel ultra-high performance liquid chromatography coupled to tandem mass …
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Accès ouvert
2025
article
OpenAlex
Ramon Guerra de Oliveira, Luiza R. Cruz, Marco A. Dessoy, Paul J. Koovits et autres
High Resolution Image Download MS PowerPoint Slide Chagas disease (CD), caused by the flagellate protozoan Trypanosoma cruzi, is a neglected tropical disease endemic in 21 countries. The only two antiparasitic drugs approved for its treatment, benznidazole and nifurtimox, have significant drawbacks. We …
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Accès ouvert
2024
article
OpenAlex
Wietse M. Schouten, Katrien Van Bocxlaer, Hilde Rosing, Alwin D. R. Huitema et autres
• DNDI-6148 is a new potential oral compound for cutaneous leishmaniasis treatment. • First validated UPLC-MS/MS methods to quantify DNDI-6148 in multiple biomatrices. • Enzymatic digestion of mouse tissue was superior over mechanical homogenization. • Protein precipitation yielded reproducible recoveries, with no …
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Accès ouvert
2024
erratum
OpenAlex
Izhar Wallach, Denzil Bernard, Kong T. Nguyen, Gregory Ho et autres
As a result, the correct Affiliation for Andrew B. Herr, Benjamin Liou, David A. Hildeman, Joseph J. Maciag, Ying Sun, Durga Krishnamurthy, and Stephen N. Waggoner is:
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2024
article
OpenAlex
A. C Silva, Jadel Muller Kratz, Priscylla G. M. Morgado, Lucio Holanda Freitas-Junior et autres
To control and decrease the public health impact of human protozoan diseases such as Chagas disease, leishmaniasis, and human African trypanosomiasis, expediting the development of new drugs and vaccines is necessary. However, this process is filled with difficulties such as highly complex …
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Accès ouvert
2024
article
OpenAlex
Brian W. Slafer, Marco A. Dessoy, Ramon Guerra de Oliveira, María C. Mollo et autres
High Resolution Image Download MS PowerPoint Slide Chagas disease (CD) is a parasitic neglected tropical disease (NTD) caused by the protozoan Trypanosoma cruzi that affects 6 million people worldwide, often resulting in financial burden, morbidity, and mortality in endemic regions. Given a …
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Accès ouvert
2024
article
OpenAlex
Izhar Wallach, Denzil Bernard, Kong T. Nguyen, Gregory Ho et autres
High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy …
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Accès ouvert
2023
article
OpenAlex
Verena Battisti, Julia Moesslacher, Rana Abdelnabi, Pieter Leyssen et autres
The worldwide re-emerge of the Chikungunya virus (CHIKV), the high morbidity associated with it, and the lack of an available vaccine or antiviral treatment make the development of a potent CHIKV-inhibitor highly desirable. Therefore, an extensive lead optimization was performed based on …
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