Nox1-dependent ROS production is crucial for cell signaling, growth, angiogenesis, motility, and blood pressure regulation. ML171 effectively inhibits ROS generation in HT29 cells (IC50=0.129 µM), and only an increased over-expression of Nox1 can counteract the suppression of ROS production by ML171 in a HEK293 cell system outfitted with all elements necessary for Nox1-dependent ROS production. ML171 significantly reduces ROS output, as indicated by carboxy-H2-DCFDA staining, with efficacy comparable to DPI, the positive control. In the HEK293-Nox1 reconstituted cell system, ML171 demonstrates enhanced effectiveness in inhibiting Nox1-dependent ROS generation compared to the original compound[1].
体外研究
Nox1-dependent ROS production is crucial for cell signaling, growth, angiogenesis, motility, and blood pressure regulation. ML171 effectively inhibits ROS generation in HT29 cells (IC50=0.129 µM), and only an increased over-expression of Nox1 can counteract the suppression of ROS production by ML171 in a HEK293 cell system outfitted with all elements necessary for Nox1-dependent ROS production. ML171 significantly reduces ROS output, as indicated by carboxy-H2-DCFDA staining, with efficacy comparable to DPI, the positive control. In the HEK293-Nox1 reconstituted cell system, ML171 demonstrates enhanced effectiveness in inhibiting Nox1-dependent ROS generation compared to the original compound[1].
ML171/2-乙酰基吩噻嗪 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Vascular smooth muscle cells (VSMC)
0.5 μM
30 minutes
To evaluate the effect of ML171 on vascular contractile responses, results showed ML171 reduced AngII-induced vascular contraction
Br J Pharmacol. 2015 Jun;172(12):3159-76.
Human platelets
10 nM-10 μM
10 minutes
To assess the effect of 2-APT on superoxide ion generation in platelets. Results showed that 2-APT significantly inhibited collagen- and fibrinogen-dependent superoxide ion generation with IC50 values of 306 nM and 227 nM, respectively.
Br J Pharmacol. 2013 Jan;168(1):212-24.
Human platelets
5 μM
ML171 significantly suppressed ROS and TxA2 production from GPVI-activated human platelets
Redox Biol. 2014 Jan 13;2:178-86.
Mouse platelets
5 μM
2 minutes
ML171 significantly suppressed CRP-induced ROS production without significantly affecting platelet aggregation or αIIbβ3 activation
Redox Biol. 2014 Jan 13;2:178-86.
Vascular smooth muscle cells (VSMCs)
10 μM
24 hours
ML171 (a NOX1 inhibitor) inhibited VSMCs migration and proliferation in SHR, similar to the effects of RND3 overexpression.
Redox Biol. 2021 Dec 6;48:102204.
HCT116 cells
10 μM
48 hours
ML171, as a NOX1 inhibitor, was used to investigate the source of ROS induced by p20BAP31. Results showed that ML171 had a minor effect on p20BAP31-induced ROS production, while the NOX2 inhibitor apocynin significantly attenuated ROS production.
Cell Mol Biol Lett. 2023 Mar 28;28(1):25.
Rat abdominal adipose-derived mesenchymal stromal cells (aASCs)
0.5, 2.5, 5 μM
Starting at passage 2
NOX1 inhibitor ML171 reduced ROS accumulation, apoptosis, and promoted long-term expansion of aASCs.
Cell Death Dis. 2015 Apr 16;6(4):e1728.
ML171/2-乙酰基吩噻嗪 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice (C57BL/6 background)
DEN-induced HCC model
Intraperitoneal injection
25 μM (100 μl/mouse)
Twice a week for 4 weeks
To evaluate the therapeutic effect of the NOX1-specific inhibitor ML171 on DEN-induced HCC. Results showed that ML171 significantly reduced the number and size of HCC nodules and decreased the expression of inflammatory mediators.
Gastroenterology. 2019 Mar;156(4):1156-1172.e6
Mice
Nox2 knockout mice
Ex vivo perfusion
5 μM
6 minutes
Both Nox1 and Nox2 were required for collagen-mediated thrombus formation at arterial shear
Redox Biol. 2014 Jan 13;2:178-86.
Spontaneously hypertensive rats (SHR)
Spontaneous hypertension model
Oral
60 mg/kg/day
Once daily for 4 weeks
ML171 treatment had minor effects on the development of spontaneous hypertension, perivascular inflammation, or vascular fibrosis.
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