SIS3 HCl

Catalog No.S7959

SIS3 HCl Chemical Structure

Molecular Weight(MW): 489.99

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.

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  • Cultured cardiac fibroblasts infected with vector lentiviruses or EphrinB2 overexpressing lentiviruses were stimulated with specific antagonist against Stat3 (Stattic, 2.5μM) and/or Smad3 (SIS3, 1μM), respectively. The expression level of α-SMA was quantified via western blotting. In vitro experiments repeat 3 times, *P<0.05, **P<0.01.

    Circ Res, 2017, pii: CIRCRESAHA. SIS3 HCl purchased from Selleck.

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Choose Selective TGF-beta/Smad Inhibitors

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

Cell Research:

[1]

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  • 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.


    (Only for Reference)
Animal Research:

[2]

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  • Animal Models: Male C57BL/6J mice
  • Formulation: --
  • Dosages: 1, 2.5, or 5 μg/g
  • Administration: i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 97 mg/mL (197.96 mM)
Ethanol 24 mg/mL (48.98 mM)
Water 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.

Chemical Information

Molecular Weight 489.99
Formula

C28H27N3O3.HCl

CAS No. 521984-48-5
Storage powder
Synonyms N/A

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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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TGF-beta/Smad Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID