| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
SIS3 HCl is a potent and selective inhibitor of Smad3 which is a receptor-regulated intracellular protein that functions downstream of TGF-β and activin receptors and mediates their signaling, playing a role in cell proliferation, differentiation, apoptosis and formation of extracellular matrix. SIS3 can block excessive ECM production from the TGF-β1-treated normal fibroblasts and scleroderma fibroblasts, the model of cells with autocrine TGF-β signaling 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.
| ln Vitro |
(E)-SIS3 (0.3–10 μM; for 1 hour) reduces the phosphorylation of Smad3 and its interaction with Smad4 caused by TGF-beta1[1]. The expression of FN and α-SMA is significantly suppressed by (E)-SIS3 (0.1, 10, 50 μM; 30 min), but not that of Sphk2, which is stimulated by TGF-β1[2]. In primary human dermal fibroblasts, (E)-SIS3 (10 μM; 24 hours) significantly reduces the expression of palladin, which is enhanced by TWEAK, as well as α-SMA[3]. In a dose-dependent manner, (E)-SIS3 significantly inhibits L4 development at five concentrations ranging from as low as 2 µM to 50 µM (5 µM, 10 µM, 20 µM, and 50 µM)[4].
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| ln Vivo |
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: Human dermal fibroblasts Tested Concentrations: 0.3, 1, 3, 10 μM Incubation Duration: For 1 hour Experimental Results: Attenuated the TGF-beta1-induced phosphorylation of Smad3 and interaction of Smad3 with Smad4. |
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| Animal Protocol |
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| References |
[1]. Jinnin M et al. Characterization of SIS3, a novel specific inhibitor of Smad3, and its effect on transforming growth factor-beta1-induced extracellular matrix expression. Mol Pharmacol. 2006 Feb;69(2):597-607.
[2]. Zhu X, et al. Sphingosine kinase 2 cooperating with Fyn promotes kidney fibroblast activation and fibrosis via STAT3 and AKT. Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864(11):3824-3836. [3]. Liu J, et al. Topical TWEAK Accelerates Healing of Experimental Burn Wounds in Mice. Front Pharmacol. 2018 Jun 21;9:660. [4]. Li FF, et al. Identification and characterization of an R-Smad homologue (Hco-DAF-8) from Haemonchuscontortus. Parasit Vectors. 2020 Apr 3;13(1):164. |
| Molecular Formula |
C28H27N3O3.HCL
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| Molecular Weight |
489.99
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| CAS # |
521984-48-5
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| Related CAS # |
SIS3 free base;521985-36-4
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| SMILES |
O=C(N1CC2=C(C=C(OC)C(OC)=C2)CC1)/C=C/C3=C(C4=CC=CC=C4)N(C)C5=NC=CC=C53.[H]Cl
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0409 mL | 10.2043 mL | 20.4086 mL | |
| 5 mM | 0.4082 mL | 2.0409 mL | 4.0817 mL | |
| 10 mM | 0.2041 mL | 1.0204 mL | 2.0409 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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