Home TGF-beta/Smad TGF-beta/Smad inhibitor SIS3 HCl For research use only.

SIS3 HCl

SIS3, a novel specific inhibitor of Smad3, inhibits TGF-β and activin signaling by suppressing Smad3 phosphorylation without affecting the MAPK/p38, ERK, or PI3-kinase signaling pathways.

SIS3 HCl Chemical Structure

SIS3 HCl Chemical Structure

CAS No. 521984-48-5

Purity & Quality Control

SIS3 HCl Related Products

Signaling Pathway

TGF-beta/Smad Signaling Pathways

TGF-beta/Smad Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HK-2 cell Cell viability assay 5 μM 1 h Treatment with SIS3 suppressed cadmium-induced HK-2 cell death. 30804470
A549 cells Function assay 3 μM The cells in the SIS3 group displayed a spindle-shaped elongated fibroblast-like morphology. 29207055
AML12 cell line Function assay 10 μM 30 mins SIS3 blocks TGF-β-mediated phosphorylation of SMAD3 and the total SMAD2/3 levels are unchanged. 27462075
A549 cells Function assay 3 μM 4 h SIS3 significantly restored E-cadherin expression and impaired vimentin and Snail expression in the presence of TGF-β1. 24573038
MCF-7 cells Proliferation assay 2.5 μM concurrent treatment with SIS3 reduced the inhibitory effect of ellagic acid on the proliferation of MCF-7 breast cancer cells. 24528038
KB-8-5-11 cells qHTS assay P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen, Potency = 20.5962 μM. 31515284
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Biological Activity

Description SIS3, a novel specific inhibitor of Smad3, inhibits TGF-β and activin signaling by suppressing Smad3 phosphorylation without affecting the MAPK/p38, ERK, or PI3-kinase signaling pathways.
Targets
Smad3 [1]
In vitro
In vitro Addition of SIS3 attenuates the effects of TGF-β1 by reducing the transcriptional activity. SIS3 also inhibits the myofibroblast differentiation of fibroblasts by TGF-β1. SIS3 completely diminishes the constitutive phosphorylation of Smad3 as well as the up-regulated type I collagen expression in scleroderma fibroblasts, thus abolishes the ECM overexpression in the TGF-β1-treated normal dermal fibroblasts and scleroderma fibroblasts in vitro[1].
Cell Research Cell lines Normal human dermal fibroblasts, Scleroderma fibroblasts
Concentrations 0.3, 1, 3 μM
Incubation Time 72 h
Method

Normal human dermal fibroblasts are plated at a density of 105 cells/well in six-well culture plates and grown until subconfluence in MEM containing 10% FCS. Cells are quiesced by 24-h incubation in serum-free MEM, followed by incubation in serum-free medium in the presence or absence of SIS3 before the collection of cells for 72 h. Then, the cells are detached from the wells by trypsin treatment and counted using a Coulter counter.
Experimental Result Images Methods Biomarkers Images PMID
Western blot COX-2 / HMGB1 p-Smad3 / Smad3 / E-cadherin / Ck18 / Fibronectin / MMP9 24098479
Immunofluorescence KDEL / Fibronectin α-SMA / Vimentin p-Smad3 E-cadherin / α-SMA 29743238
In Vivo
In vivo SIS3 inhibits Smad3 activation in streptozotocin(STZ)-induced diabetic nephropathy in Tie2-Cre;Loxp-EGFP mice. It also reduces AGE-induced EndoMT and decreases EndoMT in STZ-induced diabetic nephropathy in Tie2-Cre;Loxp-EGFP mice. SIS3 significantly reduces collagen IV and fibronectin expression in the glomeruli and tubulointerstitium of STZ-injected Tie2-Cre;Loxp-EGFP mice, suggesting that SIS3 retards the early development of STZ-induced diabetic glomerulosclerosis and tubulointerstitial fibrosis. However, SIS3 administration does not reduce proteinuria[2].
Animal Research Animal Models Male C57BL/6J mice
Dosages 1, 2.5, or 5 μg/g
Administration i.p.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06096831 Not yet recruiting
Stroke|Cerebrovascular Disorders|Cerebrovascular Accident|Healthcare Utilization
University of Haifa|Ben-Gurion University of the Negev|Clalit Health Services|Carmel Medical Center
 November 15 2023 --
NCT05816811 Recruiting
Stroke
McMaster University
 August 1 2023 Not Applicable

Chemical Information & Solubility

Molecular Weight 489.99 Formula

C28H27N3O3.HCl
CAS No. 521984-48-5 SDF Download SIS3 HCl SDF
Smiles CN1C(=C(C2=C1N=CC=C2)C=CC(=O)N3CCC4=CC(=C(C=C4C3)OC)OC)C5=CC=CC=C5.Cl
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 98 mg/mL ( (200.0 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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