SIS3 significantly inhibited ABCB1-mediated transport of calcein
Cancer Lett. 2018 Oct 1;433:259-272.
HEK293 cells
10 µM
SIS3 significantly inhibited ABCB1-mediated transport of calcein
Cancer Lett. 2018 Oct 1;433:259-272.
KB-V-1 cells
10 µM
SIS3 significantly inhibited ABCB1-mediated transport of calcein
Cancer Lett. 2018 Oct 1;433:259-272.
Astrocytes
5 µg/mL
1 hour
Inhibit Smad3/Sox9 pathway and reduce versican expression in inflammation-induced astrocytes
Neural Regen Res. 2024 Jan;19(1):180-189.
Mouse mesenchymal stem cells (MSCs)
2 µM
15 min to 7 days
To evaluate the effect of Smad3 inhibition on TGFβ2-induced tenogenesis. Results showed that inhibiting Smad3 did not prevent tenogenesis but appeared to accelerate it.
Stem Cell Res Ther. 2021 Jan 26;12(1):88.
Human small airway epithelial cells (AEC)
3 µM
2 hours
Inhibition of SMAD3 phosphorylation, thereby suppressing the expression of CHST15 and CHST11
Signal Transduct Target Ther. 2024 Feb 14;9(1):39.
Primary microglia
10 µM
24 hours
To investigate the effect of SIS3 and LPS on inflammatory response in microglia. Results showed that both SIS3 and LPS alone or in combination significantly increased proinflammatory factors (IL-1β, IL-6, iNOS, and ROS) levels.
J Neuroinflammation. 2020 Nov 16;17(1):342.
HK-2 cells
10 µM SIS3
24 hours
To monitor autophagic flux using the tandem RFP-GFP-LC3 construct. Results showed that SIS3 significantly reduced the accumulation of yellow puncta and increased the number of red puncta, indicating the restoration of autophagic flux.
Autophagy. 2021 Sep;17(9):2325-2344.
HK-2 cells
10 ng/ml
24 hours
Inhibited Smad3 phosphorylation and reversed TGF-β1-induced downregulation of CB2R expression
Cell Death Dis. 2018 May 22;9(6):601.
CD14+ monocytes
2 µM
24 hours
Inhibition of the Smad3-dependent pathway in TGF-β signaling, reducing fibronectin and type I collagen secretion
To investigate whether AGEs can induce EndoMT, results showed that AGEs induced de novo expression of α-SMA in MMECs and loss of endothelial cell markers VE-cadherin and CD31.
Diabetes. 2010 Oct;59(10):2612-24.
Splenic NK cells
2 µM
3 hours
Inhibition of Smad3 signaling enhances NK cell differentiation and anti-cancer effector functions
Nat Commun. 2017 Mar 6;8:14677.
Bone marrow-derived NK cells
2 µM
3 hours
Inhibition of Smad3 signaling enhances NK cell differentiation and anti-cancer effector functions
Nat Commun. 2017 Mar 6;8:14677.
MPC5 cells
5 µM
30 minutes
Inhibits TGF-β1-induced Btg2 expression and Btg2-mediated podocyte EMT
To investigate whether SIS3 can block AGE-induced Smad3 activation and EndoMT, results showed that SIS3 abolished AGE-induced phosphorylation of Smad3 and inhibited EndoMT.
Diabetes. 2010 Oct;59(10):2612-24.
Primary hepatocytes
10 µM
6 hours
Inhibition of SMAD3 signaling pathway, attenuating TGF-β-induced Lpcat2/4 and Smpd3 gene expression
Hepatology. 2011 Apr;53(4):1282-93.
R482-HEK293 cells
10 µM
SIS3 significantly inhibited ABCG2-mediated transport of pheophorbide A
Cancer Lett. 2018 Oct 1;433:259-272.
H460-MX20 cells
10 µM
SIS3 significantly inhibited ABCG2-mediated transport of pheophorbide A
Cancer Lett. 2018 Oct 1;433:259-272.
H460 cells
10 µM
SIS3 significantly inhibited ABCG2-mediated transport of pheophorbide A
Cancer Lett. 2018 Oct 1;433:259-272.
MDR19-HEK293 cells
10 µM
SIS3 significantly inhibited ABCB1-mediated transport of calcein
Cancer Lett. 2018 Oct 1;433:259-272.
(E/Z)-SIS3 free base 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rats
KA-induced status epilepticus model
Intraventricular injection
0.85 μg/300 g
Once daily for 7 days
Inhibiting Smad3 phosphorylation significantly reduced the severity of KA-induced seizures and decreased GFAP/CS56 immunoreactivity
Neurosci Bull. 2020 Mar;36(3):263-276
Mice
Laser-induced retinal injury model
Intraperitoneal injection
2.5 mg/kg
Injected at 3 h before injury, at day 2 or at day 6, euthanized 24 h after each injection
To investigate the inhibitory effect of SIS3 on Smad3 phosphorylation and its impact on glial scar formation after retinal injury. Results showed that SIS3 inhibited Smad3 phosphorylation, reduced glial scar formation, and promoted Müller cell dedifferentiation.
Mol Neurodegener. 2021 Sep 30;16(1):69
Db/db mice
Type 2 diabetes and diabetic nephropathy model
Intraperitoneal injection
2.5 mg/kg/day
Once daily for 8 weeks
SIS3 treatment significantly reduced blood glucose levels and inhibited the elevation of serum creatinine, microalbuminuria, renal fibrosis, and inflammation.
To investigate whether SIS3 can inhibit EndoMT and renal fibrosis in STZ-induced diabetic nephropathy, results showed that SIS3 inhibited Smad3 activation, reduced EndoMT, and retarded the progression of diabetic nephropathy.
Diabetes. 2010 Oct;59(10):2612-24.
Mice
B16F10 melanoma and LLC lung cancer models
Intraperitoneal injection
2.5, 5, 10 μg/g
Daily for 2 weeks
Inhibition of Smad3 signaling significantly suppresses tumor growth and metastasis, enhancing NK cell anti-cancer activity
Nat Commun. 2017 Mar 6;8:14677.
Sprague-Dawley (SD) rats
Syringomyelia rat model
Intraperitoneal injection
2.8 mg/kg
Started 7 days before syringomyelia induction and continued until the end of the experiment
Inhibition of TGFβR-Smad3 pathway to alleviate the dilation of central canal and syrinx formation induced by syringomyelia
Cell Biosci. 2023 May 29;13(1):98
Sprague-Dawley rats
Parkinson's disease model
Intranigral injection
4 μg/each side
Single injection, observed for 21 days
To investigate the effect of SIS3 and LPS on motor behavior and nigrostriatal dopaminergic system. Results showed that SIS3 and LPS alone or in combination induced significant behavior deficits and dopaminergic neurodegeneration.
J Neuroinflammation. 2020 Nov 16;17(1):342.
C57BL/6 mice
Spinal cord injury model
Intraperitoneal injection
44 µg/kg
Once daily
Inhibit Smad3/Sox9 pathway, reduce versican expression after spinal cord injury, and promote axonal regeneration
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