SIS3 HCl

Catalog No.S7959 Batch:S795903

Technical Data

Formula

C₂₈H₂₇N₃O₃.HCl

Molecular Weight

489.99

CAS No.

521984-48-5

Solubility (25°C)*

In vitro

DMSO

49 mg/mL (100.0 mM)

Ethanol

3 mg/mL (6.12 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	2.45mg/ml	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	0.3mg/ml	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.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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

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].

Protocol (from reference)

Cell Assay:^{^[1]}	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.
Animal Study:^{^[2]}	Animal Models Male C57BL/6J mice Dosages 1, 2.5, or 5 μg/g Administration i.p.

Cell Assay:^{^[1]}

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.

Animal Study:^{^[2]}

Animal Models
Male C57BL/6J mice
Dosages
1, 2.5, or 5 μg/g
Administration
i.p.

References

Customer Product Validation

: , , Circ Res, 2017, 121(6):617-627

: Data from [Data independently produced by , , Cell Physiol Biochem, 2017, 44(6):2201-2211]

: Data from [Data independently produced by , , Lab Invest, 2018, doi: 10.1038/s41374-018-0091-y]

: Data from [Data independently produced by , , Biochem Biophys Res Commun, 2018, 503(2):757-762]

Selleck's SIS3 HCl has been cited by 87 publications

Vulnerability to APOBEC3G linked to the pathogenicity of deltaretroviruses [ Proc Natl Acad Sci U S A, 2024, 121(13):e2309925121]	PubMed: 38502701
Vulnerability to APOBEC3G linked to the pathogenicity of deltaretroviruses [ Proc Natl Acad Sci U S A, 2024, 121(13):e2309925121]	PubMed: 38502701
Therapeutic targeting of PLK1 in TERT promoter-mutant hepatocellular carcinoma [ Clin Transl Med, 2024, 14(5):e1703]	PubMed: 38769666
Therapeutic targeting of PLK1 in TERT promoter-mutant hepatocellular carcinoma [ Clin Transl Med, 2024, 14(5):e1703]	PubMed: 38769666
Treatment for type 2 diabetes and diabetic nephropathy by targeting Smad3 signaling [ Int J Biol Sci, 2024, 20(1):200-217]	PubMed: 38164169
Sleeve gastrectomy links the attenuation of diabetic kidney disease to the inhibition of renal tubular ferroptosis through down-regulating TGF-β1/Smad3 signaling pathway [ J Endocrinol Invest, 2024, 10.1007/s40618-023-02267-1]	PubMed: 38512446
Smad3 is essential for polarization of tumor-associated neutrophils in non-small cell lung carcinoma [ Nat Commun, 2023, 14(1):1794]	PubMed: 37002229
Smad3 is essential for polarization of tumor-associated neutrophils in non-small cell lung carcinoma [ Nature Communications-, 2023, 1794-2023)]	PubMed: None
SETD2 deficiency promotes renal fibrosis through the TGF-β/Smad signalling pathway in the absence of VHL [ Clin Transl Med, 2023, 13(11):e1468]	PubMed: 37933774
A critical role for heme synthesis and succinate in the regulation of pluripotent states transitions [ Elife, 2023, 12e78546]	PubMed: 37428012

RETURN POLICY
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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.