دورية أكاديمية
SMS121, a new inhibitor of CD36, impairs fatty acid uptake and viability of acute myeloid leukemia
| العنوان: | SMS121, a new inhibitor of CD36, impairs fatty acid uptake and viability of acute myeloid leukemia |
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| المؤلفون: | Hannah Åbacka, Samuele Masoni, Giulio Poli, Peng Huang, Francesco Gusso, Carlotta Granchi, Filippo Minutolo, Tiziano Tuccinardi, Anna K. Hagström-Andersson, Karin Lindkvist-Petersson |
| المصدر: | Scientific Reports, Vol 14, Iss 1, Pp 1-15 (2024) |
| بيانات النشر: | Nature Portfolio, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | AML, Acute myeloid leukemia, CD36, Fatty acid, Adipocyte, Medicine, Science |
| الوصف: | Abstract Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most common among children. AML is characterized by aberrant proliferation of myeloid blasts in the bone marrow and impaired normal hematopoiesis. Despite the introduction of new drugs and allogeneic bone marrow transplantation, patients have poor overall survival rate with relapse as the major challenge, driving the demand for new therapeutic strategies. AML patients with high expression of the very long/long chain fatty acid transporter CD36 have poorer survival and very long chain fatty acid metabolism is critical for AML cell survival. Here we show that fatty acids are transferred from human primary adipocytes to AML cells upon co-culturing. A drug-like small molecule (SMS121) was identified by receptor-based virtual screening and experimentally demonstrated to target the lipid uptake protein CD36. SMS121 reduced the uptake of fatty acid into AML cells that could be reversed by addition of free fatty acids and caused decreased cell viability. The data presented here serves as a framework for the development of CD36 inhibitors to be used as future therapeutics against AML. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-024-58689-1 |
| URL الوصول: | https://doaj.org/article/ea900aef07be4cb98d6a67af45956451 |
| رقم الأكسشن: | edsdoj.900aef07be4cb98d6a67af45956451 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-024-58689-1 |