دورية أكاديمية
SC83288 is a clinical development candidate for the treatment of severe malaria
| العنوان: | SC83288 is a clinical development candidate for the treatment of severe malaria |
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| المؤلفون: | Pegoraro, Stefano, Duffey, Maelle, Otto, Thomas D, Wang, Yulin, Roesemann, Roman, Baumgartner, Roland, Fehler, Stefanie K, Lucantoni, Leonardo, Avery, Vicky M, Moreno-Sabater, Alicia, Mazier, Dominique, Vial, Henri J, Strobl, Stefan, Sanchez, Cecilia P, Lanzer, Michael |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2017 |
| المجموعة: | Griffith University: Griffith Research Online |
| مصطلحات موضوعية: | Other biomedical and clinical sciences not elsewhere classified, Other health sciences not elsewhere classified |
| الوصف: | Severe malaria is a life-threatening complication of an infection with the protozoan parasite Plasmodium falciparum, which requires immediate treatment. Safety and efficacy concerns with currently used drugs accentuate the need for new chemotherapeutic options against severe malaria. Here we describe a medicinal chemistry program starting from amicarbalide that led to two compounds with optimized pharmacological and antiparasitic properties. SC81458 and the clinical development candidate, SC83288, are fast-acting compounds that can cure a P. falciparum infection in a humanized NOD/SCID mouse model system. Detailed preclinical pharmacokinetic and toxicological studies reveal no observable drawbacks. Ultra-deep sequencing of resistant parasites identifies the sarco/endoplasmic reticulum Ca2+ transporting PfATP6 as a putative determinant of resistance to SC81458 and SC83288. Features, such as fast parasite killing, good safety margin, a potentially novel mode of action and a distinct chemotype support the clinical development of SC83288, as an intravenous application for the treatment of severe malaria. ; Full Text |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2041-1723 |
| العلاقة: | Nature Communications; http://hdl.handle.net/10072/342669Test |
| DOI: | 10.1038/ncomms14193 |
| الإتاحة: | https://doi.org/10.1038/ncomms14193Test http://hdl.handle.net/10072/342669Test |
| حقوق: | © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0Test/ ; open access |
| رقم الانضمام: | edsbas.86309459 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20411723 |
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| DOI: | 10.1038/ncomms14193 |