E-Amlexanox is a specific inhibitor of IKKε and TBK1(TANK-binding kinase 1), and inhibits the IKKε and TBK1 activity determined by MBP phosphorylation with an IC50 of approximately 1-2 μM. Amlexanox (100 mg/kg, p.o.) prevents and reverses diet-induced or genetic obesity, and produces reversible weight loss in obese mice. Amlexanox also causes a significant decrease in adipose tissue mass in these mice, and an increase in circulating adiponectin. Amlexanox (25 mg/kg) significantly improves insulin sensitivity in mice with established DIO, and after four weeks of treatment, amlexanox produces marked improvements in glucose[3]. In primary bone marrow derived macrophages (BMMs), amlexanox inhibited osteoclast formation and bone resorption. At the molecular level, amlexanox suppressed RANKL-induced activation of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPKs), c-Fos and NFATc1. Amlexanox decreased the expression of osteoclast-specific genes, including TRAP, MMP9, Cathepsin K and NFATc1. Moreover, amlexanox enhanced osteoblast differentiation of BMSCs. In ovariectomized (OVX) mouse model, amlexanox prevented OVX-induced bone loss by suppressing osteoclast activity[4]. Amlexanox significantly inhibited the production of pro-inflammatory mediators, both in vitro and in vivo, while increased interleukin-10 level in LPS-activated macrophages. Mechanistically, amlexanox down-regulated nuclear factor κB and extracellular signal-regulated kinase/activator protein-1 signaling by elevating intracellular 3',5'-cyclic adenosine monophosphate (cAMP) level and subsequently activating protein kinase A[5].
United States, Alabama
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Mobile Infirmary Medical Center
Mobile, Alabama, United States, 36607
United States, Arkansas
University of Arkansas Medical School
Little Rock, Arkansas, United States, 72205
United States, California
Florence Wheeler Cancer Center
Bakersfield, California, United States, 93301
United States, Connecticut
University of Connecticut Health Center
Farmington, Connecticut, United States, 06030
United States, Florida
ICSL Clinical Studies
Melbourne, Florida, United States, 32935
United States, Illinois
Loyola University Medical Center
Maywood, Illinois, United States, 60115
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
Wayne State University School of Medicine
Detroit, Michigan, United States, 48201
United States, Tennessee
University of Tennessee
Memphis, Tennessee, United States, 38163
St. Thomas Hospital
Nashville, Tennessee, United States, 37202
United States, Texas
Arlington Cancer Center
Arlington, Texas, United States, 76012
Corpus Christi Cancer Center
Corpus Christi, Texas, United States, 78412 收起 <<
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