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].
Amlexanox/氨来呫诺 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Bone marrow-derived dendritic cells (BMDCs)
2 to 200 µM
12 hours
ALX significantly inhibited the proliferation and maturation of BMDCs, characterized by the reduced MHCII, a co-stimulatory molecule, IL12, and IL-23 expression, along with morphological alterations.
J Neuroinflammation. 2019 Mar 1;16(1):52.
Human bone marrow mesenchymal stem cells (hBMSCs)
1.5 µM
24 hours
To assess AM’s potential for improving osteogenesis, leading to increased osteogenic marker gene expression and β-catenin activity.
Int J Biol Sci. 2024 Sep 30;20(13):5254-5271.
HEC-1A cells
50, 100, 200 µM
24 hours
To evaluate the effect of Amlexanox on the proliferation of endometrial cancer cells, results showed that Amlexanox significantly inhibited the proliferation of HEC-1A cells.
Int J Biol Sci. 2025 Jan 1;21(1):143-159.
Ishikawa cells
50, 100, 200 µM
24 hours
To evaluate the effect of Amlexanox on the proliferation of endometrial cancer cells, results showed that Amlexanox significantly inhibited the proliferation of Ishikawa cells.
Int J Biol Sci. 2025 Jan 1;21(1):143-159.
THP-1 cells
100-200 µM
4 hours
To evaluate the inhibitory effect of Amlexanox on the cGAS/STING signaling pathway. Results showed that Amlexanox significantly inhibited the levels of p-p65 and p-IRF3 but enhanced TBK1 phosphorylation.
BMC Med. 2024 Mar 5;22(1):96.
NSC-34 cells
200 µM
To evaluate the inhibitory effect of Amlexanox on ALS-related toxic protein-mediated cGAS/STING signaling. Results showed that Amlexanox inhibited the levels of p-p65 and p-IRF3 but had no significant effect on TBK1 phosphorylation.
BMC Med. 2024 Mar 5;22(1):96.
Amlexanox/氨来呫诺 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c nude mice
NSCLC xenografted tumor models
Intraperitoneal injection
25 mg/kg
Twice per week
To inhibit the progression of Gefitinib-resistant NSCLC
Adv Sci (Weinh). 2024 Apr;11(15):e2305541
C57BL/6J mice
Diet-induced obese (DIO) mice
Oral gavage
25 mg/kg
Daily for 8 days
Amlexanox treatment resulted in a 17% loss of body weight, 26% reduction in blood glucose levels, 41% reduction in liver weight, and 76% reduction in hepatic lipid accumulation.
Cell Metab. 2020 Dec 1;32(6):1012-1027.e7
C57Bl/6 mice
High-fat diet-induced obese mice
Oral gavage
25 or 100 mg/kg
Daily for 12 weeks
Amlexanox treatment prevented the weight gain produced by HFD; drug-treated mice maintained weights equivalent to those of vehicle-treated control diet mice throughout 12 weeks.
Nat Med. 2013 Mar;19(3):313-21
BALB/c Nude mice
Endometrial cancer xenograft model
Intraperitoneal injection
5 mg/kg
Once daily for two weeks
To evaluate the effect of Amlexanox on tumor growth in an endometrial cancer xenograft model, results showed that Amlexanox significantly inhibited tumor growth.
Int J Biol Sci. 2025 Jan 1;21(1):143-159.
BKS-DB/Nju (db/db) mice
Type 2 diabetes painful diabetic neuropathy (PDN) model
Oral gavage
5, 25, or 100 mg/kg
Once daily for four weeks
Amlexanox, as a TBK1 inhibitor, could effectively improve neuropathic pain in PDN mice, suppress spinal cord inflammation, and improve peripheral nerve injury.
Cell Commun Signal. 2024 Jul 19;22(1):368
C57BL/6 mice
Experimental autoimmune encephalomyelitis (EAE)
Oral
50 mg/kg
Twice daily, starting on the immunization day
ALX significantly attenuated the EAE development by decreasing inflammatory infiltration and demyelination in the spinal cords, accompanied by reduced frequency of splenic pathogenic Th1 and Th17 cells and increased Tregs.
J Neuroinflammation. 2019 Mar 1;16(1):52.
C57BL/6J mice
Ovariectomized (OVX) mice
Intragastric administration
50 mg/kg and 100 mg/kg
Daily for eight weeks
To evaluate the ability of AM to enhance bone formation, suppress fat accumulation, and improve bone microarchitecture.
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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