SIS3 HCl |
| رقم الكتالوجGC17191 |
SIS3HCl هو مثبط فعال وانتقائي لـ Smad3 بتركيز IC50 يبلغ 3 ميكرومول لفسفرة Smad3.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 521984-48-5
Sample solution is provided at 25 µL, 10mM.
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SIS3 HCl is a Smad3 inhibitor that inhibits the phosphorylation of Smad3 with an IC50 of 3 μM [1].
SIS3 HCl can dose-dependently eliminate enhanced p3TP-lux luciferase activity, attenuated Smad3 phosphorylation induced by transforming growth factor (TGF-1) and the interaction between Smad3 and Smad4, but SIS3 HCl does not affect Smad2 phosphorylation. SIS3 HCl attenuates the effects of TGF-1 by reducing transcriptional activity and inhibits differentiation of adult myofibroblasts via TGF-1[1]. SIS3 HCl (10 μM) in ML-12 cells blocked TGF-β-mediated Smad3 phosphorylation, while total Smad2/3 levels remained unchanged[2].
In a study of Tie2-Cre; Loxp-EGFP mice, SIS3 HCl (2.5 mg/kg/day) inhibited Smad3 activation in streptozotocin (STZ)-induced diabetic nephropathy. SIS3 HCl eliminates endothelial mesenchymal transition, reduces renal fibrosis, and slows the progression of kidney disease[3]. SIS3 HCl (5 mg/kg) significantly reduced body weight, adiposity, and fasting blood glucose in high-fat diet-induced type 2 diabetes mellitus (T2DM) model mice, and also improved insulin sensitivity and oral glucose tolerance in mice[4].
References:
[1] Jinnin M et al. Characterization of SIS3, a novel specific inhibitor of Smad3, and its effect on transforming growth factor-beta1-induced extracellular matrix expression. Mol Pharmacol. 2006 Feb;69(2):597-607.
[2] Leiting S, Seidl S, Martinez-Palacian A, Muhl L, Kanse SM. Transforming Growth Factor-β (TGF-β) Inhibits the Expression of Factor VII-activating Protease (FSAP) in Hepatocytes. J Biol Chem. 2016 Sep 30;291(40):21020-21028.
[3] Li J et al. Blockade of endothelial-mesenchymal transition by a Smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy. Diabetes.2010 Oct;59(10):2612-24.
[4] Wang D C, Yan T T, Chen B, et al. SIS3, a good candidate for the reverse of type 2 diabetes mellitus in mice[J]. Fundamental & Clinical Pharmacology, 2021, 35(2): 389-396.
| Cell experiment [1]: | |
Cell lines | HK-2 cells |
Preparation Method | Cells were incubated with 0.1% DMSO, or 5 μM SIS3 HCl for 1 h and then incubated with or without 25 μm CdCl2 (Cd) for 30 h. The viability of cells was determined by trypan blue exclusion assay. |
Reaction Conditions | 5 μM, 1 h |
Applications | SIS3 HCl inhibited cadmium-induced HK-2 cell death. |
| Animal experiment [2]: | |
Animal models | T2DM mouse model |
Preparation Method | The diagnosed type 2 diabetic mice were randomly divided into three groups, including T2DM + saline group, T2DM + vehicle group, and T2DM + SIS3 HCl treatment group. Fasting blood glucose, oral glucose tolerance, and insulin tolerance data were measured after 45 d of continuous drug administration. |
Dosage form | 5 mg/kg, 45 days, i.p. |
Applications | SIS3 HCl significantly reduced body weight, adiposity, fasting blood glucose and also improved insulin sensitivity and oral glucose tolerance in mice. |
References: [1] Fujiki K, Inamura H, Sugaya T, Matsuoka M. Blockade of ALK4/5 signaling suppresses cadmium- and erastin-induced cell death in renal proximal tubular epithelial cells via distinct signaling mechanisms. Cell Death Differ. 2019 Nov;26(11):2371-2385. [2] Wang D C, Yan T T, Chen B, et al. SIS3, a good candidate for the reverse of type 2 diabetes mellitus in mice[J]. Fundamental & Clinical Pharmacology, 2021, 35(2): 389-396. | |
| Cas No. | 521984-48-5 | SDF | |
| Chemical Name | (E)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one hydrochloride | ||
| Canonical SMILES | CN1C(C2=CC=CC=C2)=C(C3=C1N=CC=C3)/C([H])=C([H])/C(N4CCC5=CC(OC)=C(OC)C=C5C4)=O.Cl | ||
| Formula | C28H28ClN3O3 | M.Wt | 489.99 |
| الذوبان | ≥ 49 mg/mL in DMSO, ≥ 11 mg/mL in EtOH with ultrasonic and warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0409 mL | 10.2043 mL | 20.4086 mL |
| 5 mM | 0.4082 mL | 2.0409 mL | 4.0817 mL |
| 10 mM | 0.2041 mL | 1.0204 mL | 2.0409 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 3 reference(s) in Google Scholar.)
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