SIS3 HCl

For research use only.

Catalog No.S7959

43 publications

SIS3 HCl Chemical Structure

CAS No. 521984-48-5

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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10mM (1mL in DMSO) USD 227 In stock
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Selleck's SIS3 HCl has been cited by 43 publications

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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].
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HK-2 cell NXfEbFVQS2WubDD2bYFjcWyrdImgZZN{[Xl? M4XTZ|XjiIoQvF2= MljMNUBp NGfzUHhVemWjdH3lcpQhf2m2aDDTTXM{KHO3cIDy[ZN{\WRiY3HkcYl2dS2rbnT1Z4VlKEiNLUKgZ4VtdCCmZXH0bE4> NHSxZpI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MEiwOFQ4OCd-M{C4NFQ1PzB:L3G+
A549 cells MkjUSpVv[3Srb36gZZN{[Xl? M4Xxe|Mh|ryP NGHUboxVcGViY3XscJMhcW5idHjlJHNKWzNiZ4LveZAh\Gm|cHzhfYVlKGFic4DpcoRt\S2|aHHw[YQh\WyxbnfheIVlKG[rYoLvZoxie3RvbHnr[UBud3KyaH;sc4d6Ng>? NFO3VnA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUKwO|A2PSd-MkmyNFcxPTV:L3G+
AML12 cell line NVfOO|E1TnWwY4Tpc44h[XO|YYm= M3zmZVExKM7:TR?= NHexPZo{OCCvaX7z MXHTTXM{KGKub3Prd{BVT0ZvzsKtcYVlcWG2ZXSgdIhwe3Cqb4L5cIF1cW:wIH;mJHNOSUR|IHHu[EB1cGVidH;0ZYwhW02DREKvN{Bt\X[nbIOgZZJmKHWwY3jhcodm\C5? MkPBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd2NkKwO|UoRjJ5NE[yNFc2RC:jPh?=
A549 cells NX\QNYh7TnWwY4Tpc44h[XO|YYm= NFPXbJA{KM7:TR?= M2XwcFQhcA>? M4HMS3NKWzNic3nncolncWOjboTsfUBz\XO2b4Ll[EBGNWOjZHjldolvKGW6cILld5Nqd25iYX7kJIlueGGrcnXkJJZqdWWwdHnuJIFv\CCVbnHpcEBmgHC{ZYPzbY9vKGmwIITo[UBxemW|ZX7j[UBw\iCWR1[t{tIyNg>? NHPhVoM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEW3N|A{QCd-MkS1O|MxOzh:L3G+
MCF-7 cells MoeyVJJwdGmoZYLheIlwdiCjc4PhfS=> NEn1dJIzNjVizszN NHnLT2lkd26ldYLy[Y51KHS{ZXH0cYVvfCC5aYToJHNKWzNicnXkeYNm\CC2aHWgbY5pcWKrdH;yfUBm\m[nY4Sgc4Yh\WyuYXfpZ{Bi[2mmIH;uJJRp\SCycn;sbYZmemG2aX;uJI9nKE2FRj23JIJz\WG|dDDjZY5k\XJiY3XscJMv NHfkcm89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEWyPFA{QCd-MkS1NlgxOzh:L3G+
KB-8-5-11 cells MYXxTHRUKGG|c3H5 M4L5R3Au\2y7Y3;wdo91\WmwIIP1ZpN1emG2ZYOgbYRmdnSrZnnl[EBqdiCNQj24MVUuOTFiYXTlco9k[XKlaX7vcYEh[2WubDDsbY5mNCCzSGTTJJRp\XKjcHX1eIlkKGyrYoLhdpkhe2O{ZXXuMEBRd3SnbnP5JF0hOjBwNUm2NkDPxE1w MlL1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzF3MUWyPFQoRjNzNUG1Nlg1RC:jPh?=

... Click to View More Cell Line Experimental Data
Assay
Methods Test Index PMID
Western blot
COX-2 / HMGB1; 

PubMed: 24098479     


SB431542 (10 µM) or SIS3 (30 µM) blocked TGF-β1-induced COX-2 downregulation. Cells were pretreated for 60 min with the inhibitor, and then incubated with or without TGF-β1 (5 ng/mL) for 24 h. 

p-Smad3 / Smad3 / E-cadherin / Ck18 / Fibronectin / MMP9; 

PubMed: 23430956     


Representative western blots of E-cadherin, CK18, fibronectin and MMP-9 in HepG2 and BEL7402 cells with or without SIS3.

24098479 23430956
Immunofluorescence
α-SMA / Vimentin; 

PubMed: 25793924     


Effect of LY364947 and SIS3 on the expression of EMT markers altered by TGFβ1, seen by Immunofluorescence.

KDEL / Fibronectin; 

PubMed: 29743238     


Inhibition of TGFβ signaling blocks Dex-induced intracellular fibronectin co-localization with ER stress markers in primary human TM cells. Primary human TM cells (n = 3 cell strains) were treated with Veh or Dex in the presence or absence of TGFβ-signaling inhibitors (LY364947 and SIS3) for 72 h, and cells were stained for fibronectin and KDEL (Triton-permeabilized cells). The Dex-induced intracellular fibronectin load and its co-localization with KDEL were completely blocked by TGFβ-signaling inhibitors. Scale bar = 50 micron.

E-cadherin / α-SMA ; 

PubMed: 29207055     


Co-localization of E-cad and α-SMA occurs in A549 cells as determined by immunofluorescent staining. E-cad (green) was present in the cytoplasm, FITC-stained; α-SMA (red) was present in the cytoplasm, TRITC-stained. Cell nuclei were counterstained with DAPI (blue). Scale bar, 40 μm. The cell groups were as follows: control, cells cultured in serum-free DMEM; TGF-β1, cells cultured in serum-free DMEM and exposed to 5 ng/ml TGF-β1; SIS3, cells were treated with 3 μM SIS3 (specific inhibitor of Smad3) which was added 4 h prior to 5 ng/ml TGF-β1 exposure; BMSCs-CM, BMSCs-CM was added prior to 5 ng/ ml TGF-β1 exposure. E-cad, E-cadherin (E-calcium mucins); α-SMA, α-smooth muscle actin; TRITC, tetramethyl rhodamine isothiocyanate; FITC, fluorescein isothiocyanate; DAPI, 4′,6-diamidino-2-phenylindole.

p-Smad3; 

PubMed: 29207055     


Localization of p-Smad3 occurs in the cells as shown by immunofluorescence. p-Smad3 is shown in red, TRITC-stained; counterstaining of nuclei with DAPI is shown in blue. Scale bar, 50 μm. The cell groups were as follows: control, cells cultured in serum-free DMEM; TGF-β1, cells cultured in serum-free DMEM and exposed to 5 ng/ml TGF-β1; SIS3, cells were treated with 3 μM SIS3 (specific inhibitor of Smad3) which was added 4 h prior to 5 ng/ml TGF-β1 exposure. TRITC, tetramethylrhodamine isothiocyanate; DAPI, 4′,6-diamidino-2-phenylindole.

25793924 29743238 29207055
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]
- Collapse
  • 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]
- Collapse
  • Animal Models: Male C57BL/6J mice
  • 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
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300+2% Tween 80+ddH2O
For best results, use promptly after mixing. 		5mg/mL

* 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
in 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

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03884621 Completed Other: EHP Group Stroke The Hong Kong Polytechnic University September 25 2018 Not Applicable
NCT02726685 Unknown status Other: respiratory training.|Other: sham training. Stroke Chung Shan Medical University August 1 2018 Not Applicable

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID