期刊
TRENDS IN MOLECULAR MEDICINE
卷 25, 期 10, 页码 915-929出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.molmed.2019.07.003
关键词
-
资金
- Polish National Science Centre [2018/31/B/NZ9/02433, 2018/28/C/NZ9/00171]
G protein-coupled receptors (GPCRs) are the most intensively studied drug targets, because of their diversity, cell-specific expression, and druggable sites accessible at the cell surface. Preclinical and clinical studies suggest that targeting GPCRs activated by fatty acid-derived lipids mad have potential to improve glucose homeostasis and reduce complications in patients with type diabetes (T2D). Despite the discontinued development of fasiglifam (TAK-875), the first FFA1 agonist to reach late-stage clinical trials, lipid-sensing receptors remain a viable target, albeit with a need for further characterization of their binding mode, intracellular signaling, and toxicity. Herein, we analyze general discovery trends, various signaling pathways, as well a possible challenges following activation of GPCRs that have been validated clinically to contra blood glucose levels.
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