APX-115 is a potent, orally active pan-Nox inhibitor with Ki values of 1.08 μM, 0.57 μM and 0.63 μM for Nox1, Nox2 and Nox4, respectively[1].At a concentration of 5 μM for 60 min, APX-115 almost completely inhibited the expression of pro-inflammatory and necrotic molecules in high glucose-induced mouse podocyte cell lines[2].
APX-115 free base 细胞实验
Cell Line
Concentration
Treated Time
Description
References
primary chondrocytes
10 µM
24 h
APX-115 significantly decreased IL-1β-induced ROS production and oxidative DNA damage, and most potently suppressed the expression of oxidative stress marker genes and catabolic proteases.
Antioxidants (Basel). 2022 Nov 27;11(12):2346
Murine mesangial cells (MES-13)
1 µM
30 min
To evaluate the effect of APX-115 on high glucose and angiotensin II-induced intracellular ROS generation. Results showed that APX-115 significantly inhibited high glucose and angiotensin II-induced ROS generation.
Oncotarget. 2017 Jun 16;8(43):74217-74232
APX-115 free base 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
Surgically induced osteoarthritis model by destabilization of the medial meniscus (DMM)
Intraperitoneal injection
60 mg/kg
Twice a week for 8 weeks
APX-115 significantly attenuated the severity of surgically induced osteoarthritis, reducing cartilage damage and the expression of oxidative DNA damage marker 8-oxo-dG.
Antioxidants (Basel). 2022 Nov 27;11(12):2346
C57BL/6J mice
Aging diabetic model
Oral gavage
60 mg/kg
Once daily for 12 weeks
APX-115 significantly improved insulin resistance in diabetic aging mice, reduced urinary excretion of the oxidative stress marker 8-isoprostane, and ameliorated mesangial expansion, macrophage infiltration, and expression of fibrotic molecules. Additionally, APX-115 decreased the protein expression of Nox1, Nox2, and Nox4 in the kidney and restored Klotho expression levels.
Kidney Res Clin Pract. 2024 Nov;43(6):763-773
C57BL/6J mice
Streptozotocin (STZ)-induced type 1 diabetic mouse model
Oral
60 mg/kg
Once daily for 12 weeks
To evaluate the protective effect of APX-115 on diabetic kidney injury. Results showed that APX-115 significantly reduced urinary albumin excretion, glomerular hypertrophy, tubular injury, podocyte injury, fibrosis, and inflammation, and inhibited oxidative stress. Additionally, APX-115 restored mitochondrial and peroxisomal biogenesis in diabetic kidneys.
Oncotarget. 2017 Jun 16;8(43):74217-74232
APX-115 free base 动物研究
Animal study
In the kidney, APX-115 attenuated Nox gene up-regulation and protein expression while ameliorating inflammatory and fibrotic processes. Administered orally at a dose of 60 mg/kg/day for 12 weeks, APX-115 significantly improved insulin resistance in diabetic mice. APX-115 treatment reduced urinary albumin excretion and plasma creatinine levels[2].
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