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SIS3 HCl TGF-beta/Smad inhibitor

Name: SIS3 HCl
Brand: Selleck Chemicals
SKU: S7959
Availability: InStock
Rating: 5 (84 reviews)

Cat.No.S7959

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.

Chemical Structure

Molecular Weight: 489.99

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.65%

99.65

Related Targets	PKC Bcr-Abl ROCK
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Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	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
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	489.99	Formula	C₂₈H₂₇N₃O₃.HCl	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	521984-48-5	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CN1C(=C(C2=C1N=CC=C2)C=CC(=O)N3CCC4=CC(=C(C=C4C3)OC)OC)C5=CC=CC=C5.Cl

Solubility

In vitro
Batch:

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

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.400mg/ml (0.82mM)	Taking the 1 mL working solution as an example, add 50 μL of 8 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	2.450mg/ml (5.00mM)	Taking the 1 mL working solution as an example, add 50 μL of 49 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.300mg/ml (0.61mM)	Taking the 1 mL working solution as an example, add 50 μL of 6 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	Smad3 ^[1]
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].
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].
References	https://pubmed.ncbi.nlm.nih.gov/16288083/ https://pubmed.ncbi.nlm.nih.gov/20682692/

Applications

Methods	Biomarkers	Images	PMID
Western blot	COX-2 / HMGB1 p-Smad3 / Smad3 / E-cadherin / Ck18 / Fibronectin / MMP9		24098479
Immunofluorescence	α-SMA / Vimentin KDEL / Fibronectin E-cadherin / α-SMA p-Smad3		25793924

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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