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Results: NT-1044 and metformin significantly inhibited cell proliferation in a dose-dependent manner in both EC cell lines after 72 hours of exposure (IC50 218 μM for Ishikawa 87 μM for ECC-1 cells). The mice were treated with placebo or NT-1044 or metformin following tumor onset for 4 weeks. For the in vivo studies, we utilized the LKB1 fl/flp53 fl/fl mouse model of endometrioid endometrial cancer.
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Reactive oxygen species (ROS) were measured using DCFH-DA and JC-1 assays. Cell cycle progression was evaluated by Cellometer. Apoptosis was analyzed by Annexin V-FITC and cleaved caspase 3 assays. Methods: Cell proliferation was assessed in two EC cell lines, ECC-1 and Ishikawa, by MTT assay after exposure to NT-1044 for 72 hours of treatment.
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We sought to compare the effects of NT-1044 on cell proliferation in human endometrial cancer (EC) cell lines and on tumor growth in an endometrioid EC mouse model.
#STRONGEST AMPK ACTIVATOR ACTIVATOR#
Metformin requires organic cation transporters (OCTs) for entry into cells, and NT-1044 is an AMPK activator designed to have greater affinity for two of these transporters, OCT1 and OCT3. Objectives: Anti-diabetic biguanide drugs such as metformin may have anti-tumorigenic effects by behaving as AMPK activators and mTOR inhibitors. 4Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.3NovaTarg Therapeutics, First Flight Venture Center, Durham, NC, United States.2Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.1Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.Batchelor 3, Chunxiao Zhou 1,4* and Victoria L. Wysham 1†, Jianjun Han 2, Wenchuan Sun 1, Yajie Yin 1, James N.