GLPBio

SIS3 HCl

Catalog No.: GC17191Purity:>98.00%
COASDSData Sheet
SIS3 HCl is a Smad3 inhibitor that inhibits the phosphorylation of Smad3 with an IC50 of 3 μM.

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SIS3 HCl
Cas No.: 521984-48-5
2mgIn Stock
$50.00
1
5mgIn Stock
$73.00
1
25mgIn Stock
$227.00
1
500mgIn Stock
$2,173.00
1
1gIn Stock
$3,475.00
1
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Description

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.

Protocol

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.

Product Documents

Purity:>98.00%Appearance:A solid
COASDSData Sheet

Chemical Properties

CAS No.
521984-48-5
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
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
Molecular Formula
C28H28ClN3O3
Molecular Weight
489.99
Solubility
≥ 49 mg/mL in DMSO, ≥ 11 mg/mL in EtOH with ultrasonic and warming
Storage
Store at -20°C
General tips
Select a suitable solvent according to the product solubility data. Once prepared, aliquot the stock solution to avoid repeated freeze-thaw cycles.
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
Shipping Condition
Evaluation samples are shipped with blue ice. Other available sizes are shipped at room temperature or with blue ice upon request.

CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility

g/mol

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