Azeliragon (TTP488) is an orally bioavailable inhibitor of the receptor for advanced glycation end products (RAGE) and is currently under development as a treatment option to potentially slow the progression of mild Alzheimer’s disease (AD)[1]. Azeliragon also can cross the blood-brain barrier (BBB)[2].
体内研究
Furthermore, Azeliragon administered intraperitoneally at a dosage of 100 mcg/day, effectively reduces both syngeneic islet grafts and islet allografts in NOD and B6 mice. These mice models include NOD/LtJ mice with spontaneous diabetes receiving islets from young prediabetic NOD/LtJ mice, and diabetic B6 mice receiving islets from WT BALB/c mice, showcasing its potential in immunological applications beyond neurodegenerative disease[3].
体外研究
In experimental settings, Azeliragon (at a concentration of 4 nM for 16 hours) has been shown to inhibit the activation of wild type mouse (WT) T cells while not affecting RAGE-deficient mice (RAGE-/-). This treatment also significantly reduces the production of IFN-γ, indicating its potential impact on immune modulation in neurological contexts[3].
Azeliragon/阿齐瑞格 细胞实验
Cell Line
Concentration
Treated Time
Description
References
4175 and 4T1 cells
1 µM
24 hours
To evaluate the effect of RAGE inhibitors on cell invasion and migration, results showed that Azeliragon significantly reduced invasion and migration of 4175 and 4T1 cells
NPJ Breast Cancer. 2023 Jul 13;9(1):59.
4T1 cells
0.05–1 μM
24, 48, 72 hours
To evaluate the effect of RAGE inhibitors on cell proliferation and viability, results showed that Azeliragon and FPS-ZM1 did not affect cell proliferation or viability in vitro
NPJ Breast Cancer. 2023 Jul 13;9(1):59.
MDA-MB-231/4175 cells
0.05–1 μM
24, 48, 72 hours
To evaluate the effect of RAGE inhibitors on cell proliferation and viability, results showed that Azeliragon and FPS-ZM1 did not affect cell proliferation or viability in vitro
NPJ Breast Cancer. 2023 Jul 13;9(1):59.
Human umbilical vein endothelial cells (HUVECs)
1 to 5 μmol/L
12 hours
To evaluate the effect of the RAGE antagonist Azeliragon (TTP488) on AGE-mediated KLF2 suppression. Results showed that TTP488 prevented the suppression of KLF2 mRNA by CML-BSA with an EC50 of 1.9 μmol/L.
J Am Heart Assoc. 2018 Jan 4;7(1):e007566.
Pan02 cells
0.05–3 µM
24 hours
To evaluate the effect of Azeliragon on the proliferation of Pan02 cells, results showed that Azeliragon inhibited cell proliferation in a dose-dependent manner
Cancers (Basel). 2024 Dec 24;17(1):17.
Panc1 cells
0.05–3 µM
24 hours
To evaluate the effect of Azeliragon on the proliferation of Panc1 cells, results showed that Azeliragon inhibited cell proliferation in a dose-dependent manner
Cancers (Basel). 2024 Dec 24;17(1):17.
Azeliragon/阿齐瑞格 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NSG mice
4175/NSG orthotopic xenograft model
Intraperitoneal injection
1 mg/kg
Twice weekly until tumor volume reached ~500 mm³
To evaluate the effect of Azeliragon on tumor growth and metastasis, results showed that Azeliragon significantly reduced lung metastasis
NPJ Breast Cancer. 2023 Jul 13;9(1):59.
Mice
ApcMin/+ mouse model
Oral
4 mg/kg
Not specified
To evaluate the inhibitory effect of Azeliragon on tumor growth and MDSC infiltration, results showed Azeliragon significantly suppressed tumor growth and reduced MDSC infiltration.
Gut. 2025 Jan 17;74(2):214-228.
C57BL/6 mice
GL261 glioma model
Intraperitoneal injection
0.2 mg/kg
Once daily for 25 days
To evaluate the therapeutic effect of Azeliragon on glioblastoma, the results showed that Azeliragon treatment significantly improved the survival rate of mice and reduced tumor proliferation.
Theranostics. 2025 Jan 1;15(2):726-744
NU/NU mice and C57BL/6NJ mice
Pancreatic cancer model
Intraperitoneal injection
1 mg/kg
Daily administration until mice survived
To evaluate the anti-tumor activity of Azeliragon alone or in combination with radiation therapy in pancreatic cancer mouse models, results showed that Azeliragon alone or in combination with RT significantly delayed tumor growth and prolonged survival
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